Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone- analyses based on the Huizhou mother-infant cohort.

Objectives: This study aimed to explore the relationship of maternal thyroid function and thyroid resistance parameters with neonatal thyroid-stimulating hormone (TSH). Methods: This work was a longitudinal study. Singleton pregnant women without a history of thyroid disorders were recruited in their first prenatal visit from October 2018 to June 2020. Maternal thyroid markers including TSH, free triiodothyronine (FT3), free thyroxine (FT4), and neonatal TSH were tested in the clinical laboratory of the hospital by electrochemiluminescence immunoassay. Thyroid resistance indices including Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI) were estimated in accordance with maternal FT4 and TSH levels. Multivariable linear and logistic regression was applied to explore the associations of maternal thyroid indices with infantile TSH level. Results: A total of 3,210 mothers and 2,991 newborns with valid TSH data were included for analysis. Multivariable linear regression indicated that maternal thyroid variables were significantly and positively associated with neonatal TSH levels with standardized coefficients of 0.085 for TSH, 0.102 for FT3, 0.100 for FT4, 0.076 for TSHI, 0.087 for TFQI, and 0.089 for TT4RI (all P < 0.001). Compared with the lowest quartile, the highest quartile of TSHI [odds ratio (OR) = 1.590, 95% CI: 0.928-2.724; Ptrend = 0.025], TFQI (OR = 1.746, 95% CI: 1.005-3.034; Ptrend = 0.016), and TT4RI (OR = 1.730, 95% CI: 1.021-2.934; Ptrend = 0.030) were significantly associated with an increased risk of elevated neonatal TSH (>5 mIU/L) in a dose-response manner. Conclusion: The longitudinal data demonstrated that maternal thyroid resistance indices and thyroid hormones in the first half of gestation were positively associated with neonatal TSH levels. The findings offered an additionally practical recommendation to improve the current screening algorithms for congenital hypothyroidism.

The 6-month effect of whole soy and purified isoflavones daidzein on thyroid function-A double-blind, randomized, placebo controlled trial among Chinese equol-producing postmenopausal women.

The aim of this study was to examine the effect of whole soy and purified daidzein on markers of thyroid function in Chinese postmenopausal women who were equol-producers. Total 270 eligible women were randomized to either one of the three isocaloric supplements: 40 g soy flour (whole soy group), 40 g low-fat milk powder +63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo) daily for 6 months. Serum thyroid markers were tested at baseline and 6 months for thyroid stimulating hormone, free triiodothyronine, reverse triiodothyronine and free thyroxine (FT4). There was no significant difference in the 6-month changes of thyroid markers among the three groups. Subgroup analysis among women with lowered thyroid function suggested a modest decrease of FT4. This randomized controlled trial among Chinese equol-producing postmenopausal women indicates the consumption of whole soy and purified daidzein at the provided dosages are safe and have no detrimental effect on thyroid function.

Effect of whole soy and isoflavones daidzein on bone turnover and inflammatory markers: a 6-month double-blind, randomized controlled trial in Chinese postmenopausal women who are equol producers.

BACKGROUND: Human studies have demonstrated the beneficial effects of soy or isoflavones on bone metabolism. However, conflicting data remain. Equol is the intestinal metabolite of the isoflavone daidzein. The health benefits of soy are more pronounced in equol producers than those not producing equol. This 6-month randomized controlled trial aimed to examine the effect of whole soy (soy flour) and purified daidzein on bone turnover markers (BTMs) in Chinese postmenopausal women who are equol producers. METHODS: A total of 270 eligible women were randomized to either one of the three isocaloric supplements as follows: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) given as a solid beverage daily for 6 months. The following fasting venous samples were collected at the baseline and end of the trial to analyze BTMs: serum cross-linked C-telopeptides of type I collagen, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and 25(OH)D3. Inflammation-related biomarkers, such as serum interleukin-6, tumor necrosis factor-alpha, C-reactive protein, transferrin, and homocysteine, were also tested to explore potential mechanisms. RESULTS: A total of 253 subjects validly completed the study protocol. Urinary isoflavones suggested a good compliance to the treatments. Intention-to-treat and per-protocol analyses indicated no significant difference in the 6-month or percentage changes in the parameters of bone metabolism and inflammatory markers among the three treatment groups. CONCLUSIONS: Whole soy and purified daidzein at provided dosages exhibited no significant effect on the bone metabolism and inflammation levels among Chinese equol-producing postmenopausal women. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01270737.

Effect of whole soy and purified daidzein on androgenic hormones in chinese equol-producing post-menopausal women: a six-month randomised, double-blinded and Placebo-Controlled trial.

A randomised, double-blind and placebo-controlled trial was performed to examine the effects of whole soy and isoflavone daidzein on serum androgenic hormones in Chinese equol-producing post-menopausal women. A total of 270 eligible women aged 45-70 years were randomised to either one of the three iso-caloric supplements: 40 g soy flour (whole soy group), 40 g low-fat milk powder +63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily for 6 months. Fasting venous samples were tested for serum androstenedione (AD), testosterone (T), prolactin, sex hormone binding globulin and dehydroepiandrosterone sulphate. Intention-to-treat analysis indicated that serum T (p = .022) and AD (p = .05) levels modestly but significantly decreased after 6-month daidzein treatment in comparison with placebo, with a mean difference of -0.057 nmol/L (95%CI: -0.185 to 0.070, p = .018) and -0.118 ng/mL (95%CI: -0.240-0.004, p = .045), respectively. This 6-month trial suggested that purified daidzein may exhibit less androgenic effect.Trial registration: The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737.).

Serum Bioavailable, Rather Than Total, 25-hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival.

BACKGROUND AND AIMS: Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. APPROACH AND RESULTS: We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum-free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable-adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CONCLUSIONS: Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis.

Serum folate concentrations at diagnosis are associated with hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort study.

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.

Higher serum carotenoids associated with improvement of non-alcoholic fatty liver disease in adults: a prospective study.

PURPOSE: Previous studies have suggested that serum carotenoids might be inversely associated with non-alcoholic fatty liver disease (NAFLD), but little data came from longitudinal studies. We prospectively examined the associations between serum-carotenoid levels and NAFLD severity and the intermediary effects of retinol-binding protein 4 (RBP4), HOMA insulin-resistance index (HOMA-IR), body mass index (BMI), and serum triglycerides in middle-aged and elderly Chinese adults. METHODS: This prospective study included 3336 Chinese adults (40-75 years). We assessed serum concentrations of carotenoids at baseline and determined serum RBP4, triglycerides, and HOMA-IR levels at year 3. Abdominal ultrasonography was conducted to assess the presence and degree of NAFLD at years 3 and 6. RESULTS: The 2687 subjects who completed both NAFLD tests were classified into stable, improved and progressed groups according to changes in the degree of NAFLD between two visits. Analyses of covariance showed that ln-transformed serum concentrations of α-carotene, ß-cryptoxanthin, ß-carotene, lycopene, lutein/zeaxanthin, and total carotenoids were positively associated with NAFLD improvement (all p-trend < 0.05). After multivariable adjustment, mean differences in serum carotenoids were higher by 29.6% (ß-carotene), 18.2% (α-carotene), 15.6% (ß-cryptoxanthin), 11.5% (lycopene), 8.9% (lutein/zeaxanthin), and 16.6% (total carotenoids) in the improved vs. progressed subjects. Path analyses indicated the carotenoid-NAFLD association was mediated by lowering serum RBP4, triglycerides, HOMA-IR, and BMI, which were positively associated with the prevalence and progression of NAFLD. CONCLUSIONS: In middle-aged and elderly adults, higher serum-carotenoid concentrations were favorably associated with NAFLD improvement, mediated by reducing serum RBP4, triglycerides, HOMA-IR, and BMI. TRIAL REGISTRATIONS: This study has been registered at http://www.clinicaltrials.gov as NCT03179657.

Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort.

Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22-2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36-3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89-1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99-2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.

Higher dietary and serum carotenoid levels are associated with lower carotid intima-media thickness in middle-aged and elderly people.

Several studies have suggested that higher carotenoid levels may be beneficial for atherosclerosis patients, but few studies have examined this relationship in the Chinese population. This cross-sectional study examined the association between the levels of carotenoids in diet and serum and carotid intima-media thickness (IMT) in Chinese adults aged 50-75 years in Guangzhou, China. Dietary intake was assessed using a FFQ. HPLC was used to assay the serum concentrations of α-carotene, ß-carotene, lutein+zeaxanthin, ß-cryptoxanthin and lycopene. The IMT at the common carotid artery (CCA) and bifurcation of the carotid artery was measured by B-mode ultrasound. A total of 3707 and 2947 participants were included in the analyses of dietary and serum carotenoids. After adjustment for demographic, socio-economic and lifestyle factors, all the serum carotenoids levels except lycopene were found to be inversely associated with the IMT at the CCA and bifurcation (P trend<0·001 to 0·013) in both men and women. The absolute mean differences in the IMT between the subjects in the extreme quartiles of serum carotenoid levels were 0·034 mm (α-carotene), 0·037 mm (ß-carotene), 0·032 mm (lutein+zeaxanthin), 0·030 mm (ß-cryptoxanthin), 0·015 mm (lycopene) and 0·035 mm (total carotenoids) at the CCA; the corresponding values were 0·025, 0·053 0·043, 0·050, 0·011 and 0·042 mm at the bifurcation. The favourable associations were also observed between dietary carotenoids (except lycopene) and the CCA IMT. In conclusion, elevated carotenoid levels in diet and serum are associated with lower carotid IMT values (particular at the CCA) in Chinese adults.

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1.

Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues. Using both overexpression and knockdown of COX-2, we demonstrated that the localization of COX-2 at mitochondria promotes the stemness of NPC by recruiting the mitochondrial translocation of p53, increasing the activity of Drp1 and inducing mitochondrial fisson. Inhibition of the expression or the activity of Drp1 by siRNA or Mdivi-1 downregulates the stemness of NPC. The present study also found that inhibition of mitochondrial COX-2 with resveratrol (RSV), a natural phytochemical, increased the sensitivity of NPC to 5-fluorouracil (5-FU), a classical chemotherapy drug for NPC. The underlying mechanism is that RSV suppresses mitochondrial COX-2, thereby reducing NPC stemness by inhibiting Drp1 activity as demonstrated in both the in vitro and the in vivo studies. Taken together, the results of this study suggest that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC.

Randomised controlled trial of effect of whole soy replacement diet on features of metabolic syndrome in postmenopausal women: study protocol.

INTRODUCTION: Metabolic syndrome (MetS) is a public health problem in postmenopausal women. Whole soy foods are rich in unsaturated fats, high quality plant protein and various bioactive phytochemicals that may have a beneficial role in the management of MetS. The aim of the study is to examine the effect of whole soy replacement diet on the features of MetS among postmenopausal women. METHODS AND ANALYSIS: This will be a 12-month, randomised, single-blind, parallel controlled trial among 208 postmenopausal women at risk of MetS or with early MetS. After 4 weeks' run-in, subjects will be randomly allocated to one of two intervention groups, whole soy replacement group or control group, each for 12 months. Subjects in the whole soy group will be required to include four servings of whole soy foods (containing 25 g soy protein) into their daily diet iso-calorically, replacing red or processed meat and high fat dairy products. Subjects in the control group will remain on a usual diet. The outcome measures will include metabolic parameters as well as a 10-year risk for ischaemic cardiovascular disease. We hypothesise that the whole soy substitution diet will notably improve features of MetS in postmenopausal women at risk of MetS or with early MetS. The study will have both theoretical and practical significance. If proven effective, the application of the whole soy replacement diet model will be a safe, practical and economical strategy for MetS prevention and treatment. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee of the Chinese University of Hong Kong. The results will be disseminated via conference presentations and papers in academic peer reviewed journals. Data files will be deposited in an accessible repository. TRIAL REGISTRATION NUMBER: NCT02610322.

Research protocol: effect of natural S-equol on blood pressure and vascular function--a six-month randomized controlled trial among equol non-producers of postmenopausal women with prehypertension or untreated stage 1 hypertension.

BACKGROUND: Although higher habitual soy intake is associated with lower blood pressure (BP) and stroke incidence, clinical trials using soy protein or isoflavones on cardiovascular risks yielded inconsistent results. The discrepancies are hypothesized to be due to the individuals' intestinal bacterial capacity to metabolite isoflavones daidzein into equol. Animal and in vitro studies have revealed that equol has stronger estrogen-like and anti-oxidative activity than isoflavones and possesses natriuretic and vasorelaxant properties which may play an important role in the prevention of hypertension. However, no clinical trial has examined the effect of equol on BP. We thus propose a 24-week randomized controlled trial to test the effectiveness of natural S-equol on BP and vascular function among equol non-producers. METHODS/DESIGN: This will be a 6-month double-blind, randomized, placebo-controlled trial among 207 non-equol producing postmenopausal women with prehypertension or early untreated hypertension. Eligible participants who have completed a 2-week run-in will be randomized to either one of the 3 groups: placebo group, low-equol group (10 mg/d) and high equol group (20 mg/d). The outcome measures will be conducted at baseline and at the end of the trial including 24 h ambulatory BP, endothelial function (by ultrasound determined brachial flow mediated dilation), arterial stiffness (by pulse wave analysis) and other cardiovascular risk factors (lipid profile, glycemic control and inflammatory biomarkers). Urinary isoflavones will be tested for compliance assessment. One way analysis of variance will be applied to compare the 6-month changes in ambulatory BP or parameters of vascular function among the 3 treatment groups. DISCUSSION: This study will be performed in community subjects. If the antihypertensive effect of equol is proven, the provision of natural equol to those high risk adults who are unable to produce equol will have enormous public health implications for the primary and secondary prevention of hypertension and cardiovascular diseases on a population basis. The research efforts will also have significant implications for industry in the provision of suitable soy products for the prevention of hypertension and its related complications. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov with identifier of NCT02515682 .

Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults.

Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18-60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants.

[The Role of FGF21 in Regulating Lipid and Glucose Metabolism].

Fibroblast growth factor 21 (FGF21), a member of fibroblast growth factor superfamily has received extensive attention for its positive effect on metabolism. Many tissues are target of FGF21 action. The effect of FGF21 on improving lipid and glucose metabolism has been proved. It also suggests that FGF21 plays a conspicuous role in a state of prolonged fasting and starvation. This article will review the role of FGF21 in regulating lipid and glucose metabolism and discuss the involved cellular and molecular mechanisms.

Greater serum carotenoid levels associated with lower prevalence of nonalcoholic fatty liver disease in Chinese adults.

Previous studies have suggested that serum carotenoids may be inversely associated with liver injury, but limited data are available from population-based studies. We examined the relationship between serum carotenoid levels and the prevalence of nonalcoholic fatty liver disease (NAFLD) in Chinese adults. A total of 2935 participants aged 40-75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of carotenoid and the presence and degree of NAFLD were determined. After adjusting for potential covariates, we observed a dose-dependent inverse association between NAFLD risk and each individual serum carotenoid and total carotenoids (all p-values < 0.001). The ORs of NAFLD for the highest (vs. lowest) quartile were 0.44 (95% CI 0.35, 0.56) for α-carotene, 0.32 (95% CI 0.25, 0.41) for ß-carotene, 0.62 (95% CI 0.49, 0.79) for ß-cryptoxanthin, 0.54 (95% CI 0.42, 0.68) for lycopene, 0.56 (95% CI 0.44, 0.72) for lutein + zeaxanthin and 0.41 (95% CI 0.32, 0.53) for total carotenoids. Higher levels of α-carotene, ß-carotene, lutein + zeaxanthin and total carotenoids were significantly associated with a decrease in the degree of NAFLD (p-trend: < 0.001 to 0.003). Serum carotenoids are inversely associated with prevalence of NAFLD in middle aged and elderly Chinese.

A CONSORT-compliant, randomized, double-blind, placebo-controlled pilot trial of purified anthocyanin in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that can progress to cirrhosis and liver failure. Anthocyanin, a member of the flavonoid family, has been shown to ameliorate NAFLD-associated pathologies in rodents.The aim of this CONSORT-compliant pilot study is to evaluate the effects of anthocyanin supplementation on insulin resistance and liver injury biomarkers in patients with NAFLD.A total of 74 subjects with NAFLD were divided into 2 groups in this double-blind, randomized study. Patients received either purified anthocyanin (320 mg/d) derived from bilberry and black currant or placebo for 12 weeks. Diet, physical activity, anthropometric parameters, glucose tolerance, and a set of biomarkers related to NAFLD were evaluated before and after intervention.No significant differences were observed in nutrient intake, physical activity, anthropometric parameters, or plasma lipid profile between patients receiving anthocyanin or placebo. Compared to controls, the anthocyanin group exhibited significant decreases (P < 0.05, all comparisons) in plasma alanine aminotransferase (-19.1% vs 3.1%), cytokeratin-18 M30 fragment (-8.8% vs 5.6%) and myeloperoxidase (-75.0% vs -44.8%). Significant decreases from baseline in fasting blood glucose and homeostasis model assessment for insulin resistance were observed in the anthocyanin group; however, these differences were not significant relative to placebo controls. In addition, the oral glucose tolerance test indicated that anthocyanin supplementation significantly decreased the 2-hour loading glucose level compared to control (-18.7% vs -3.8%, P = 0.02).A 12-week supplement of purified anthocyanin improved insulin resistance, indicators of liver injury, and clinical evolution in NAFLD patients. Further studies are warranted to determine the clinical applications of anthocyanin in NAFLD.This trial was registered at clinicaltrials.gov as NCT01940263.

Parthenolide inhibits cancer stem-like side population of nasopharyngeal carcinoma cells via suppression of the NF-κB/COX-2 pathway.

Cancer stem cells play a central role in the pathogenesis of nasopharyngeal carcinoma and contribute to both disease initiation and relapse. In this study, cyclooxygenase-2 (COX-2) was found to regulate cancer stem-like side population cells of nasopharyngeal carcinoma cells and enhance cancer stem-like cells' characteristics such as higher colony formation efficiency and overexpression of stemness-associated genes. The regulatory effect of COX-2 on cancer stem-like characteristics may be mediated by ABCG2. COX-2 overexpression by a gain-of-function experiment increased the proportion of side population cells and their cancer stemness properties. The present study also demonstrated that in contrast to the classical chemotherapy drug 5-fluorouracil, which increased the proportion of side population cells and upregulated the expression of COX-2, parthenolide, a naturally occurring small molecule, preferentially targeted the side population cells of nasopharyngeal carcinoma cells and downregulated COX-2. Moreover, we found that the cancer stem-like cells' phenotype was suppressed by using COX-2 inhibitors NS-398 and CAY10404 or knocking down COX-2 with siRNA and shRNA. These findings suggest that COX-2 inhibition is the mechanism by which parthenolide induces cell death in the cancer stem-like cells of nasopharyngeal carcinoma. In addition, parthenolide exhibited an inhibitory effect on nuclear factor-kappa B (NF-κB) nucler translocation by suppressing both the phosphorylation of IκB kinase complex and IκBα degradation. Taken together, these results suggest that parthenolide may exert its cancer stem cell-targeted chemotherapy through the NF-κB/COX-2 pathway.

The role of sodium-dependent glucose transporter 1 and glucose transporter 2 in the absorption of cyanidin-3-o-ß-glucoside in Caco-2 cells.

Anthocyanins have multiple biological activities of benefit to human health. While a few studies have been conducted to evaluate the bioavailability of anthocyanins, the mechanisms of their absorption mechanism remain ill-defined. In the present study, we investigated the absorption mechanism of cyanidin-3-O-ß-glucoside (Cy-3-G) in human intestinal epithelial (Caco-2) cells. Cy-3-G transport was assessed by measuring the absorptive and efflux direction. Inhibition studies were conducted using the pharmacological agents, phloridzin, an inhibitor of sodium-dependent glucose transporter 1 (SGLT1), or phloretin, an inhibitor of glucose transporter 2 (GLUT2). The results showed that phloridzin and phloretin significantly inhibited the absorption of Cy-3-G. In addition, Caco-2 cells transfected with small interfering RNA (siRNA) specific for SGLT1 or GLUT2 showed significantly decreased Cy-3-G absorption. These siRNA transfected cells also showed a significantly decreased rate of transport of Cy-3-G compared with the control group. These findings suggest that Cy-3-G absorption is dependent on the activities of SGLT1 and GLUT2 in the small intestine and that SGLT1 and GLUT2 could be a limiting step for the bioavailability of Cy-3-G.

Higher serum carotenoid concentrations associated with a lower prevalence of the metabolic syndrome in middle-aged and elderly Chinese adults.

The association between serum carotenoids and the metabolic syndrome (MetS) remains uncertain, and little is known about this relationship in the Chinese population. The present study examined the association between serum carotenoid concentrations and the MetS in Chinese adults. We conducted a community-based cross-sectional study in which 2148 subjects (1547 women and 601 men) aged 50-75 years were recruited in urban Guangzhou, China. Dietary data and other covariates were collected during face-to-face interviews. Blood pressure, waist circumference, blood lipids, glucose and serum carotenoids (α-, ß-carotene, ß-cryptoxanthin, lycopene and lutein/zeaxanthin) were examined. We found dose-response inverse relationships between individual serum carotenoid concentrations and total carotenoids and the prevalence of the MetS after adjusting for potential confounders (P for trend < 0.001). The OR of the MetS for the highest (v. lowest) quartile were 0.31 (95% CI 0.20, 0.47) for α-carotene, 0.23 (95% CI 0.15, 0.36) for ß-carotene, 0.44 (95% CI 0.29, 0.67) for ß-cryptoxanthin, 0.39 (95% CI 0.26, 0.58) for lycopene, 0.28 (95% CI 0.18, 0.44) for lutein+zeaxanthin and 0.19 (95% CI 0.12, 0.30) for total carotenoids. Higher concentrations of each individual carotenoid and total carotenoids were significantly associated with a decrease in the number of abnormal MetS components (P for trend < 0.001-0.023). Higher serum carotenoid levels were associated with a lower prevalence of the MetS and fewer abnormal MetS components in middle-aged and elderly Chinese adults.

Association of simple anthropometric indices and body fat with early atherosclerosis and lipid profiles in Chinese adults.

OBJECTIVE: The discriminatory capability of different adiposity indices for atherosclerosis and lipid abnormalities remains uncertain. This study aimed to identify the best adiposity index for predicting early atherosclerosis and abnormal lipid profiles among anthropometric parameters and body fat measures in middle-aged and elderly Chinese. METHOD: A total of 2,063 women and 814 men (57.6±5.2 y) were recruited for this community-based cross-sectional study. Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were assessed. Body fat mass and its percentage values for the whole body and trunk were measured by bioelectrical impedance analysis (BIA). The intima-media thicknesses (IMTs) of the common carotid arteries (CCA), internal carotid arteries (ICA) and bifurcation (BIF) were determined via B-mode ultrasound. The fasting lipid profiles were assessed. RESULTS: With per SD increase of adiposity indices, the magnitude of the changes of IMT values and lipid profiles was more substantial for WC, WHR and WHtR in both genders. A multivariate logistic regression analysis indicated that WC, WHR and WHtR were more sensitive in predicting the presence of intima-media thickening at the three segments as well as the lipids disturbances in women and men. In general, BIA-derived measures have no added predictive value for IMT-thickening as opposed to those three traditional abdominal measures. CONCLUSION: Our findings suggest that abdominal anthropometric measures including WC, WHR and WHtR are sensitive for discriminating carotid atherosclerosis and lipids abnormalities. WC is the best index because of its simplicity in routine use.