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Background The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold. Objectives We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and genetic factors with risks of total and subtypes of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. Methods This prospective study included 15,103 individuals with T2D who were initially free of CVD and had serum 25(OH)D measurements in the UK Biobank. Incidences of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke. Results The mean serum 25(OH)D concentration was 43.4 nmol/L (SD: 20.4 nmol/L), and 65.7% of participants had a vitamin D concentration below 50 nmol/L. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had HRs (95% CIs) of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D concentrations ≥50 nmol/L and low GRSs, as compared with individuals with 25(OH)D concentrations <25 nmol/L and high GRSs, had a 50% (39%, 65%) lower risk of IHD. No significant interactions were demonstrated between serum 25(OH)D concentrations and the GRSs and genetic variants in vitamin D receptors (VDR). Conclusions Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of their genetic susceptibility and the genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmol/L. These findings suggest that maintaining an adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D. [ABSTRACT FROM AUTHOR]

Background Although low-carbohydrate and low-fat diets are beneficial in short-term metabolic improvement, the associations of these dietary patterns, particularly with different food sources and quality of macronutrients, with mortality remain unclear among people with prediabetes. Objectives We aimed to examine the associations of different types of lower-carbohydrate diets (LCDs) and lower-fat diets (LFDs) with mortality among individuals with prediabetes. Methods This study included 9793 adults with prediabetes from the NHANES 1999–2014. Mortality status was linked to National Death Index mortality data through 31 December, 2015. Overall, unhealthy, and healthy LCD and LFD scores were determined based on the percentages of energy from total and subtypes of carbohydrate, fat, and protein. Cox proportional hazards regression models were applied to calculate HRs and 95% CIs. Results Higher healthy LCD score was associated with favorable blood glucose, insulin, HOMA-IR, C-reactive protein (CRP), and blood lipids, whereas higher healthy LFD score was associated with lower blood glucose and CRP at baseline (all P -trend < 0.05). During 72,054 person-years of follow-up, 1352 deaths occurred. The multivariate-adjusted HRs (95% CIs) of all-cause mortality per 20-percentile increment in dietary scores were 0.88 (0.80, 0.96) for healthy LCD score (P  = 0.003), 0.85 (0.78, 0.93) for healthy LFD score (P  < 0.001), 1.09 (0.99, 1.21) for unhealthy LCD score (P  = 0.08), and 1.11 (1.00, 1.22) for unhealthy LFD score (P  = 0.05). Isocalorically replacing 3%–5% energy of low-quality carbohydrate or saturated fat with high-quality carbohydrate, plant-based protein, or unsaturated fat was associated with a 14%–37% reduced all-cause mortality. Conclusions Healthy LCD and LFD scores were significantly associated with lower all-cause mortality, whereas unhealthy LCD and LFD scores tended to be associated with higher all-cause mortality, among people with prediabetes. [ABSTRACT FROM AUTHOR]

Background Knowledge of glycemic status may affect dietary intake for subjects with diabetes and prediabetes. Objectives We aimed to determine whether trends of macronutrient intake and dietary quality differed by diagnosis of glycemic status among US adults with diabetes and prediabetes. Methods Data from NHANES 1999–2016 were analyzed. Diagnosed cases were established by self-report, and undiagnosed cases were defined by laboratory criteria (glycated hemoglobin ≥ 5.7%, fasting plasma glucose ≥ 100 mg/dL, or 2-h oral-glucose-tolerance test ≥ 140 mg/dL). A difference-in-differences model was used to compare the temporal trends between the 2 groups. Results There were 7502 diagnosed and 12,974 undiagnosed cases with elevated glycemic status included in the study. During 1999–2016, the intake of low-quality carbohydrates was lower, whereas intakes of high-quality carbohydrates, animal protein, plant protein, and unsaturated fat and the Healthy Eating Index 2015 (HEI-2015) score were higher, among the diagnosed cases than among the undiagnosed cases (P  < 0.001 for all). However, in the trend analyses from 1999 to 2016, the increase in intake of high-quality carbohydrates was smaller among the diagnosed cases than among the undiagnosed cases (difference: −1.16%; 95% CI: −1.82%, −0.50%; P  = 0.001). Moreover, the decrease in low-quality carbohydrate intake was smaller (difference: 0.79%; 95% CI: 0.01%, 1.57%; P  = 0.05) and the increase in saturated fat intake was larger (difference: 0.44%; 95% CI: 0.08%, 0.79%; P  = 0.02) among the diagnosed cases than among the undiagnosed cases. A significant difference of temporal trends in the HEI-2015 score between the diagnosed and undiagnosed cases was also observed, in favor of the undiagnosed cases (difference: −2.56; 95% CI: −3.71, −1.41; P  < 0.001). Conclusions Although dietary habits among adults with diagnosed diabetes and prediabetes were better than those among the undiagnosed cases, these advantages have been diminishing during the past 2 decades. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies consistently find associations between whole-grain intake and reduced risk of obesity and related metabolic diseases, yet data on the potential of whole grains to prevent fatty liver diseases are scarce.Objectives: To examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with nonalcoholic fatty liver disease (NAFLD).Methods: This case-control study of Chinese adults enrolled 940 NAFLD cases and 940 age- and sex-matched non-NAFLD controls (mean age: 55.2 y; 65% males). NAFLD diagnosis was defined as individuals whose hepatic ultrasound disclosed hepatic steatosis at any stage, after the exclusion of alcohol abuse and other liver diseases. Fasting plasma DHPPA concentration was measured by LC-MS/MS. Multivariate adjusted ORs and 95% CIs were estimated to assess the association between plasma DHPPA and NAFLD using conditional logistic regression.Results: Plasma concentration of DHPPA was significantly lower in patients with NAFLD compared with controls (median: 9.86 nmol/L compared with 10.9 nmol/L, P = 0.002). In multivariable logistic regression models, the ORs (95% CIs) for NAFLD across increasing tertiles of plasma DHPPA were 1 (reference), 0.76 (0.54, 1.05), and 0.65 (0.45, 0.93), respectively (P-trend = 0.026). In addition, the inverse associations persisted in subgroups stratified by sex, age, BMI, abdominal adiposity, smoking status, physical activity, diabetes, hypertension, and hyperlipidemia.Conclusions: These results indicate that increased plasma DHPPA concentration is associated with lower risk of NAFLD in Chinese adults, independently of well-known risk factors. Our finding provides evidence to support health benefits of whole-grain consumption on NAFLD. This trial was registered at clinicaltrials.gov as NCT03845868. [ABSTRACT FROM AUTHOR]

Background The impact of selenium status on the long-term health of people with type 2 diabetes (T2D) remains unclear. Objectives To prospectively examine the association of serum selenium concentrations with all-cause and heart disease mortality among individuals with T2D. Methods This analysis included 3199 adults with T2D from the third NHANES (NHANES III) and NHANES (2003–2004, 2011–2014). Mortality from heart disease and all causes was linked to National Death Index mortality data. Cox proportional hazard models were used to estimate HRs and 95% CIs. Results The median (IQR) concentration of serum selenium was 127.0 (115.0, 139.1) µg/L. During an average 12.6-y follow-up, 1693 deaths were documented, including 425 heart disease deaths. Compared with participants in the lowest quartile of selenium, the multivariate-adjusted HRs (95% CIs) for participants in the highest quartile were 0.69 (0.54, 0.89) for all-cause mortality (P -trend = 0.002) and 0.66 (0.45, 0.99) for heart disease mortality (P -trend = 0.03). In addition, a linear dose–response relation between serum selenium (range: 89–182 µg/L) and mortality was observed. For per-unit increment in natural log-transformed serum selenium, there was a 64% lower risk of all-cause mortality and a 66% lower risk of heart disease mortality (both P  < 0.05). Similar results were observed when stratifying by age, sex, race, smoking status, BMI, physical activity, diabetes duration, and HbA1c concentrations. Conclusions Our study suggested that higher selenium concentration was associated with lower all-cause and heart disease mortality among individuals with T2D. More studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background Several individual studies have shown that circulating levels of odd-chain SFAs and very-long-chain SFAs (VLSFAs) may have beneficial effects, but the results are mixed. While the dietary and metabolic factors that may influence VLSFAs are not well-known, a previous study observed associations of VLSFA concentrations with variants in serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3) gene. Objectives We investigated the associations of individual plasma SFAs and SPTLC3 gene rs680379 polymorphism with metabolic risk factors and type 2 diabetes (T2D). Methods We measured plasma SFAs using gas chromatography among 898 T2D cases and 1618 matched controls, and genotyped the SPTLC3 gene rs680379 polymorphism using the MassArray System among 1178 T2D cases and 1907 matched controls. Conditional logistic regression was used to estimate ORs and 95% CIs. Results We found that plasma odd-chain SFAs and VLSFAs were correlated with favorable blood lipids and insulin resistance marker profiles. After multivariable adjustment, pentadecanoic acid (15:0) was inversely associated with the odds of T2D (OR per 1 SD difference: 0.63; 95% CI: 0.57, 0.70), as were measurements of 3 individual VLSFAs [arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)], with ORs ranging from 0.60 to 0.72 (95% CIs ranging between 0.52 and 0.79). The associations between 3 individual VLSFAs and T2D were attenuated after further adjustment for triglycerides. Meanwhile, compared with the rs680379 GG genotype carriers, the ORs of T2D for the GA and AA genotype carriers were 0.81 (95% CI: 0.68–0.97) and 0.76 (95% CI: 0.61–0.96), respectively. Conclusions Plasma 15:0 and VLSFAs were inversely associated with T2D. Meanwhile, compared with the rs680379 GG genotype carriers, subjects with GA and AA genotypes were associated with decreased odds of T2D. More investigations are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Iron is an essential trace element to almost all organism, and the delicate balance between host defend system and viral proliferation plays an important role in infective conditions. While the association of the iron metabolism with the prognosis of COVID-19 remains poorly understood. We aimed to estimate the associations of systemic iron metabolism parameters with the severity and risks of adverse outcomes in COVID-19. In this retrospective cohort study, we included 158 confirmed COVID-19 patients in Tongji Hospital, Wuhan, China (27 January to 5 April, 2020). Demographic data, comorbidities, laboratory examinations, treatments, and clinical outcomes were all collected. Multivariable Poisson regression was used to estimate the association of iron parameter levels with the severity and risks of adverse outcomes in COVID-19 patients. We identified 60 (38%) severe cases in 158 COVID-19 patients. The median age was 63 years (interquartile range [IQR]: 54–73) and the median length of hospital stay was 28 days (IQR: 17–40). After adjusting for age, sex, IL-6, and pre-existing comorbidities, all iron parameters were associated with the severity of COVID-19 with adjusted risk ratio of 0.42 [95% CI: 0.22–0.83], 4.38 [95% CI: 1.86–10.33], 0.19 [95% CI: 0.08–0.48], and 0.25 [95% CI: 0.10–0.58] for serum iron, ferritin, transferrin, and total iron-binding capacity, respectively. These iron indices were also related to the risk of ARDS, coagulopathy, acute cardiac injury, acute liver injury, and acute kidney injury in COVID-19 patients and high cytokine concentrations. Patients with low serum iron status likely suffered from severe condition and multiple–organ injury in COVID-19. The iron metabolism parameters might be risk factors and clinical biomarkers for COVID-19 prognosis. [ABSTRACT FROM AUTHOR]

Drinking water and food are the major sources of strontium in human. Strontium is essential for bone metabolism, while its role in glucose and lipid metabolism is largely unknown. We aimed to investigate the association of strontium, a bone-seeking element, with type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) and to further explore the potential mechanisms. The case-control study included 1448 newly diagnosed T2DM patients, 782 IGR patients, and 2230 matched controls with normal glucose tolerance. Plasma strontium and other plasma minerals were quantified via inductively coupled plasma mass spectrometry. Multivariable logistic regression analysis was used to evaluate the independent associations between plasma strontium and T2DM and IGR. Plasma strontium was inversely associated with T2DM and IGR. After adjustment for sociodemographic, lifestyle factors, and multiple plasma metals, the odds ratios (95% confidence intervals) of T2DM and IGR were 0.45 (0.35–0.57) and 0.55 (0.43–0.71), respectively, comparing the highest to the lowest quartile of plasma strontium levels. In spline analysis, the odds of T2DM and IGR decreased remarkably with increasing strontium concentration and followed by a plateau. Additionally, plasma strontium was negatively associated with total cholesterol, low density lipoprotein cholesterol, and lipid peroxidation (plasma malondialdehyde level). The current study indicated that higher plasma strontium concentration was associated with lower odds of T2DM and IGR. Further studies are warranted to confirm these findings and to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives: The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods: A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography–tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results: Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions: Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Quercetin is a natural functional component distributed in vegetables, fruits and red wine. • Lysosome damage mediated autophagy dysfunction played an important role in ALD. • Quercetin promoted TFEB nuclear translocation to enhance lysosomal function. • mTOR-TFEB pathway may be a major mechanism of the protection of quercetin. Abstract This study aimed to investigate the effects of quercetin that is natural functional component in food on lysosome damage-mediated autophagy dysfunction in ALD and its possible underlying mechanisms. The C57BL/6J mice were divided into four groups and pair-fed with either regular or ethanol-containing Lieber De Carli liquids diets for 15 weeks. Quercetin was received by gavage. According to the purpose of experiments, primary hepatocytes were pretreated with various pharmacological reagents. Results showed that quercetin alleviated chronic ethanol consumption induced liver injury and autophagic flux suppression. Quercetin decreased the abnormal LC3-II and p62 accumulation and increased the expression of LAMP1, LAMP2 and Rab7. Besides, quercetin reversed the inhibition of TFEB nuclear translocation incited by ethanol and exhibited similar effect to Torin 1 (mTOR activity inhibitor) which could promote TFEB nuclear translocation. Thus, regulating mTOR-TFEB pathway may be a major mechanism of quercetin for ameliorating lysosomal autophagy dysfunction induced by ethanol. [ABSTRACT FROM AUTHOR]

[Display omitted] • Alginate promotes weight loss in overweight adults, compared to maltodextrin. • Alginate decreased body fat in overweight subjects and did not affect lean mass. • Bile acid and related gut microbiota were changed after alginate intervention. • Alterations in gut microbiota were linked to weight loss induced by alginate. Being overweight is a risk for various chronic diseases. Alginate, a soluble dietary fiber extracted from seaweed, has been linked to weight loss with unclear mechanisms. We conducted a double-blind, randomized trial in overweight or normal-weight adults to explore alginate's weight loss effect and mechanism. Normal-weight or overweight participants were randomized to receive either alginate (15 g/day) or maltodextrin (13.8 g/day) for 14 weeks. Compared to maltodextrin (−0.91 kg; 95% CI, −1.91 to 0.10), alginate helped overweight subjects lose weight (−2.67 kg; 95% CI, −3.89 to −1.46) (P = 0.0017) after 14 weeks. In overweight subjects, alginate increased fecal-conjugated bile acids (taurocholate acid and taurochenodeoxycholic acid) and reduced bile acid-related bacteria (Bacteroides , Oscillibacter and Eubacterium). Our results indicate that alginate decreases weight and increases bile acid excretion in overweight subjects, related to gut microbiota alterations and inhibited intestinal bile acid absorption. [ABSTRACT FROM AUTHOR]

Background: The microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been reported as a novel and independent risk factor for the development of cardiovascular and metabolic diseases, but the association with gestational diabetes mellitus (GDM) remains unclear. Objective: The aim of this study was to investigate the association between plasma TMAO concentration and GDM in a 2-phase study. Design: A 2-phase design was used in the current study. An initial phase included 866 participants (433 GDM cases and 433 matched controls) with fasting blood samples collected at the time of GDM screening (24–32 wk of gestation). An independent-phase study,with 276 GDM cases and 552 matched controls who provided fasting blood samples before 20 wk of gestation and who hadGDMscreened during 24–32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted inWuhan, China, and the incidence of GDM in the cohort study was 10.8%. Plasma TMAO concentrations were determined by stable isotope dilution liquid chromatography–tandem mass spectrometry. GDM was diagnosed according to the American Diabetes Association criteria by using an oral-glucose-tolerance test. Results: In the initial case-control study, the adjusted OR of GDM comparing the highest TMAO quartile with the lowest quartile was 1.94 (95% CI: 1.28, 2.93). Each SD increment of ln-transformed plasma TMAO was associated with 22% (95% CI: 5%, 41%) higher odds of GDM. In the nested case-control study, women in the highest quartile also had increased odds of GDM (adjusted OR: 2.06; 95% CI: 1.28, 3.31) compared with women in the lowest quartile, and the adjusted OR for GDM per SD increment of ln-transformed plasma TMAO was 1.26 (95% CI: 1.08, 1.47). Conclusions: Consistent findings from this 2-phase study indicate a positive association between plasma TMAO concentrations and GDM. Future studies are warranted to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Hepatic steatosis and insulin resistance are highly prevalent and play a vital role in the development of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The present study examined the protective effects of naturally occurring flaxseed lignan secoisolariciresinol diglucoside (SDG) on these metabolic disorders resulting from high fat diet (HFD). SDG (0.05%, w/w) supplementation for 16 weeks attenuated body weight gain, hyperlipidaemia and hepatic steatosis in HFD (60% kcal from fat)-challenged C57BL/6J mice. Moreover, SDG lowered fasting serum glucose and insulin, and improved homeostasis model assessment of insulin resistance (HOMA-IR) index, glucose tolerance, and insulin response in HFD-fed mice. Furthermore, SDG prevented HFD-induced inhibition of protein kinase B, insulin receptor substrate-1 and AMP-activated protein kinase activation in the liver of HFD-fed mice. These findings indicate that SDG supplementation alleviates hepatic steatosis and insulin resistance, at least in part, by enhancing insulin signalling and AMPK activation. [ABSTRACT FROM AUTHOR]

Aims It is evident that adverse childhood experiences (ACEs) can influence health status of adult life, but few large-scale studies have assessed the relation of ACEs with type 2 diabetes. This meta-analysis aimed to summarize existing evidence on the link between ACEs and type 2 diabetes in adults. Materials and method We searched all published studies from PubMed and EMBASE before Aug 2015 using keywords like adverse childhood experiences and diabetes, and scanned references of relevant original articles. We included studies that reported risk estimates for diabetes by ACEs and matched our inclusion criteria. We examined the overall relationship between ACEs and diabetes, and stratified the analyses by type of childhood adversities, study design and outcome measures, respectively. Results Seven articles fulfilled the inclusion criteria for this Meta-analysis, comprising 4 cohort and 3 cross-section studies. A total of 87,251 participants and 5879 incident cases of type 2 diabetes were reported in these studies. The exposure of ACEs was positively associated with the risk of diabetes with a combined odds ratio of 1.32 (95% confidence interval 1.16 to 1.51) in the total participants. The influence of neglect was most prominent (pooled odds ratio 1.92, 95% confidence interval 1.43 to 2.57) while the effect of physical abuse was least strong (pooled odds ratio 1.30, 95% confidence interval 1.19 to 1.42). The pooled odds ratio associated with sexual abuse was 1.39 with the 95% confidence intervals from 1.28 to 1.52. Conclusions The results support a significant association of adverse childhood experiences with an elevated risk of type 2 diabetes in adulthood. [ABSTRACT FROM AUTHOR]

The prevalence of non-alcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Dietary flaxseed oil and plant sterol exert potential benefit to NAFLD. Present study was designed to evaluate the effects of flaxseed oil containing flaxseed oil ester of plant sterols (FO-PS) on hepatic steatosis induced by high fat diet (HFD) and investigate the underlying molecular mechanisms. C57BL/6 mice were administered a regular diet (RG) and apoE−/− mice were given HFD alone or plus 5% flaxseed oil with or without 3.3% FO-PS for 18 weeks. Our data showed that HFD induced NAFLD while dietary flaxseed oil fortified with FO-PS offered a synergistically effective strategy for improving hepatic steatosis as well as optimizing overall lipid levels, reducing oxidative stress and inhibiting system inflammation. The expression levels of hepatic genes involved in cholesterol efflux (ABCA1, LXR, SR-BI) and triacylglycerol catabolism (PPARα) were also increased significantly by intervention of flaxseed oil plus FO-PS. In addition, combination treatment reduced ROS production and down-regulated inflammatory markers (IL-6, TNF, MCP-1 and ICAM-1) in liver. Thus, dietary supplementation of flaxseed oil containing FO-PS altered the expressions of genes related to lipid metabolism and inflammation, and thus ameliorated hepatic steatosis. [ABSTRACT FROM AUTHOR]

Abstract: Naturally occuring quercetin protects hepatocytes from ethanol-induced oxidative stress, and heme oxygenase-1 (HO-1) induction and carbon monoxide (CO) metabolite may be implicated in the beneficial effect. However, the precise mechanism by which quercetin counteracts CYP2E1-mediated ethanol hepatotoxicity through HO-1 system is still remained unclear. To explore the potential mechanism, herein, ethanol (4.0g/kg.bw.) was administrated to rats for 90 days. Our data showed that chronic ethanol over-activated CYP2E1 but suppressed HO-1 with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg.bw.). Quercetin (100μM) induced HO-1 and depleted heme pool when incubated to human hepatocytes. Ethanol-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by HO-1 inhibition with resultant heme accumulation. CO scavenging blocked the suppression of quercetin only on CYP2E1 activity. CO donor dose-dependently inactivated CYP2E1 of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger. Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by quercetin through HO-1 induction. Depleted heme pool and CO releasing limited protein synthesis and inhibited enzymatic activity of CYP2E1, respectively. [Copyright &y& Elsevier]

Abstract: Our previous study found that curcumin, a major active component of turmeric, could ameliorate ethanol-induced hepatocytes oxidative stress in vitro. The objective of this work was to investigate the effect of curcumin on chronic alcoholic liver disease (ALD) in vivo. Ethanol-exposed (2.4g/kg/day ethanol for the initial 4 weeks and 4g/kg/day for another 2 weeks) Balb/c mice were simultaneously treated with curcumin for 6 weeks. The results showed that curcumin attenuated ethanol-induced histopathological changes of the liver and ameliorated the evident release of cellular alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Ethanol exposure resulted in reactive oxygen species (ROS) generation, malondialdehyde (MDA) elevation, glutathione (GSH) depletion and antioxidant defense system impairment, which were significantly reversed by curcumin treatment. In conclusion, curcumin provided protection against chronic ALD and the mechanism might be related to the alleviation of oxidative damage. [Copyright &y& Elsevier]

[Display omitted] • Yeast protein improved muscle histologically and ultrasonically and increased myofiber size. • Yeast protein promoted muscle protein synthesis and muscle regeneration and differentiation. • The composition and diversities of gut microbiota were altered by yeast protein. • Yeast protein-induced gut microbiota changes were closely involved in the process of muscle aging. There may be close links among yeast protein (Saccharomyces cerevisiae) supplementation, gut microbiota and skeletal muscle aging. In present study, nineteen-month-old mice received yeast protein (1.0 g/kg/d) for three months by gavage. Histological and ultrasonographical improvements in muscle as well as an increase in myofiber size were observed after yeast protein supplementation. Moreover, yeast protein activated Akt/mTOR/4E-BP1 pathway and regulated myogenic regulatory factors (Myog, Myf4, Myf5, and Myod1) to promote muscle protein synthesis and muscle regeneration and differentiation. Meanwhile, alpha and beta diversities as well as the ratio of Firmicutes and Bacteroidetes were elevated after yeast protein supplementation. Changes in the abundance of gut microbiota after yeast protein supplementation were significantly correlated with glycan biosynthesis and metabolism, amino acid metabolism and lipid metabolism, closely involved in the process of muscle aging. Hence, yeast protein supplementation could contribute to ameliorating muscle aging, which may be associated with gut microbiota. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the effects of lotus seedpod proanthocyanidins (LSPC) administration by oral gavage for 3 months on body weight, learning and memory deficits using Y-maze test, oxidative stress and antioxidative enzyme activity in brain and serum of the senescence-accelerated mice (SAMP8) and the senescence-resistant mice (SAMR1). Mice of each group were weighed weekly. Brain was obtained from SAMP8 and SAMR1 (the control mouse for SAMP8) at 6 months of age and serum was available from SAMP8 and SAMR1 at 3, 4, 5 and 6 months of age. The results of body weight showed that 90mg/kg LSPC administration significantly increased body weight at 5.5 and 6 months of age in SAMP8 when compared with control SAMP8 of the same age. Y-maze test indicated that learning and memory abilities of mice were deteriorated significantly at 6 months of age in SAMP8 compared with age-matched SAMR1, but were remarkably improved after LSPC (60, 90, 120mg/kg body weight) administration beginning at 3 months of ages. Malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) exhibited significant increases mostly at 5 and 6 months of age in SAMP8. Glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities decreased significantly mostly at 5 and 6 months of age in SAMP8. LSPC (60, 90, 120mg/kg body weight) administration beginning at 3 months of ages decreased MDA, NO content and lowered NOS activity in the brain and serum of SAMP8. Furthermore, LSPC significantly increased GSH level and augmented GPx, SOD activity in the brain and serum of SAMP8. These results suggest that an age-related increase in brain tissue vulnerability to oxidation and deterioration in learning and memory abilities in SAM that can be modified by LSPC, most likely through the ability of LSPC to scavenge oxygen free radicals and to stimulate antioxidant enzyme activity. [Copyright &y& Elsevier]

Abstract: We investigated the protective effects of diallyl disulfide (DADS), a potent inhibitor of cytochrome P450 2E1 (CYP2E1), on ethanol-induced toxicity in human hepatocytes. We found a clear dose-dependent response between ethanol and CYP2E1 activity. The ethanol-dependent CYP2E1 enzyme activity and protein expression, lactate dehydrogenase and aspartate transaminase release, malondialdehyde formation and caspase-3 activity decreased dramatically in the presence of DADS. Furthermore, DADS increased the hepatocellular glutathione (GSH) content and prevented the ethanol-dependent cellular GSH depletion. Our data show that DADS reduces ethanol-induced toxicity in human hepatocytes by reducing CYP2E1 activity and/or stabilizing the cellular GSH content, which might be of therapeutic interest. [Copyright &y& Elsevier]

• Interactions between metal(loid)s and gut microbiota vary greatly. • Generalizations cannot be easily made between single metal(loid) and gut microbiota. • Microbiota-related strategies are effective in metal(loid) detoxification. • Human intervention trials for microbiota-related strategies are urgently warranted. Human exposure to metal(loid)s has dramatically increased over the past five decades, which has triggered public concern worldwide. Recently, gut microbiota has been considered a target for metal(loid)s, and some literature has reviewed the interactions between gut microbiota and heavy metal(loid)s (HMs) with high toxicity. However, whether there is an interaction between gut microbiota and metal(loid)s with essential roles or some normal functions are far from clear to date. Importantly, in addition to traditional probiotics that have been clarified to alleviate the adverse effect of HMs on the body, some novel probiotics, prebiotics, synbiotics, and postbiotics may also exhibit comparable or even better abilities of metal(loid) remediation. In this review, we mainly outline and discuss recent research findings on the metal(loid)-gut microbiota interactions and microbiota-related protective strategies. [ABSTRACT FROM AUTHOR]

Background/Aims: Flavonoids, including quercetin, have been reported to have potent hepatoprotective effects, which may be associated with HO-1 induction. However, since the effect and signaling pathway of quercetin involved in HO-1 induction against alcoholic liver damage are still not fully understood, this is the target of the present study. Methods: Human hepatocytes were incubated with ethanol (100mM) and quercetin (10–200μM), and cellular damage and HO-1 activity were measured. Nrf2 expression in cytosolic and nuclear fractions was studied following the incubation with MAPK inhibitor(s). Results: Ethanol exposure resulted in a sustained glutathione depletion, malondialdehyde elevation, and evident release of cellular LDH and AST. Quercetin exerted a dose-dependent protective effect against alcoholic oxidative stress, and increased the EC50 of ethanol by approx. 40%, which is parallel to HO-1 induction with quercetin. Zinc protoporphyrin-9 abrogated the protective effect and dramatically enhanced ethanol cytotoxicity. SB203580 (p38 inhibitor) and especially PD98059 (ERK inhibitor) blocked quercetin-derived HO-1 induction and Nrf2 translocation, and subsequently inhibited the quercetin-related protection. Conclusions: HO-1 up-regulation by quercetin protected human hepatocytes from ethanol-induced oxidative stress. Among MAPK signaling pathways, p38 and ERK mediated quercetin-derived Nrf2 translocation into nuclei and subsequent induction of HO-1 activity, and the latter showed a stronger mediating effect. [Copyright &y& Elsevier]

Physical activity (PA) and telomeres both contribute to healthy aging and longevity. To investigate the optimal dosage of various PA for longevity and the role of telomere length in PA and mortality. Prospective cohort study. A total of 333,865 adults (mean age of 56 years) from the UK Biobank were analyzed. Walking, moderate PA (MPA), and vigorous PA (VPA) were self-reported via questionnaire, and leukocyte telomere length (LTL) was measured. Cox proportional hazards regression was used to predict all-cause mortality risk. A flexible parametric Royston-Parmar survival model was used to estimate life expectancy. During a median follow-up of 13.8 years, 19,789 deaths were recorded. Compared with the no-walking group, 90 to 720 minutes/week of walking was similarly associated with 27% to 31% of lower mortality and about 6 years of additional life expectancy. We observed nearly major benefits for mortality and life expectancy among those meeting the PA guidelines [151-300 minutes/wk for MPA: hazard ratio (HR) 0.80, 95% CI 0.75-0.85, 3.40-3.42 additional life years; 76-150 minutes/wk for VPA: HR 0.78, 95% CI 0.75-0.82, 2.61 years (2.33-2.89)] vs the no-PA group. Similar benefits were also observed at 76-150 and 301-375 minutes/wk of MPA (18%-19% lower mortality, 3.20-3.42 gained years) or 151-300 minutes/wk of VPA (20%-26% lower mortality, 2.41-2.61 gained years). The associations between MPA, VPA, and mortality risk were slightly mediated by LTL (≈1% mediation proportion, both P <.001). Our study suggests a more flexible range of PA than the current PA guidelines, which could gain similar benefits and is easier to achieve: 90 to 720 minutes/wk of walking, 75 to 375 minutes/wk of MPA, and 75 to 300 minutes/wk of VPA. Telomeres might be a potential mechanism by which PA promotes longevity. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that remarkably imposes a huge global public health burden. Yeast β-glucans have been incorporated in functional foods and used in prophylactic applications owing to their biological effects. However, few studies had investigated the effects of yeast β-glucans on neurodegenerative diseases. Here, gut microbiota and metabolites SCFAs were analyzed through high-throughput 16S rRNA gene sequencing and GC–MS, respectively. Results indicated that yeast β-glucans could prominently shape the intestinal flora and produce SCFAs. Aβ 1 – 42 -induced AD mice treated with small-molecular yeast β-glucan (S-β-Glu) or macro-molecular yeast β-glucan (M-β-Glu) exhibited evident alterations of the composition of the gut microbiota, especially in some beneficial bacteria and inflammatory-related bacteria such as Lactobacillus , Bifidobacterium , Desulfovibrio , Oscillibacter , Mucispirillum , Alistipes , Anaerotruncus , and Rikenella. M-β-Glu regulated gut microbiota act as prebiotics better than S-β-Glu. Correlation analysis demonstrated the key microbiota closely associated with AD-related pathologies and cognition. Moreover, M-β-Glu and S-β-Glu ameliorated neuroinflammation and brain insulin resistance (IR), which played a central role in the process of AD pathology. This study broadened the underlying applications of yeast β-glucans as a novel dietary supplementation to prevent early-stage pathologies associated with AD by regulating gut microbiota and the potential mechanism might be ameliorating brain IR. Unlabelled Image • Yeast β-glucans improved cognition deficits and pathological changes in AD-like mice. • Yeast β-glucans might ameliorate cognitive dysfunction through gut-brain axis. • Yeast β-glucans increased SCFAs levels and restored gut microbiota dysbiosis. • M-β-Glu could better regulate intestinal flora acting as prebiotics than S-β-Glu. • Yeast β-glucans ameliorated AD-like symptoms by alleviating inflammation and brain IR. [ABSTRACT FROM AUTHOR]

Abstract Background Consumptions of DON-contaminated food by farm animals and humans lead to mycotoxicoses. Based on the previous studies, DON may cause the morphological, numerical and functional abnormity of erythrocyte in animals such as pigs, poultry, horses, mice, humans and so on. But at present, there is still a lack of full and systematic discussion of the DON-induced erythrocyte damage. Scope and approach Therefore, the aim of the present review is to summarize and update the prominent evidences, explore possible mechanisms, put forward preventive measures, and suggest a hypothesis for future research regarding the effects of DON on erythrocyte. Key finding And conclusions what we summarize are 1) Apart from ruminant, DON can induce erythrocyte damage in animals and there is a threshold level about damage. However, the value of threshold level and the extent of damage are still unclear; 2) DON exerts toxicity on erythrocyte mainly by penetrating the phospholipid bilayers, interacting with the cellular membranes, and phospholipid peroxidation. Most probably, more than one mechanism operates at the same time; 3) The existing methods for preventing damage can be classified as reducing absorption of DON through intestinal tract and blocking mechanisms that DON exerts toxicity on erythrocyte. Highlights • DON-contaminated food by farm animals and humans lead to mycotoxicoses. • Lack of full and systematic discussion of the DON-induced erythrocyte damage. • Mechanism 1) Penetration of the probably passes the phospholipid bilayers. • Mechanism 2) Interaction between the toxin and the cell membranes. • Mechanism 3) Free radical(s) mediated phospholipid peroxidation. [ABSTRACT FROM AUTHOR]

Abstract Background Deoxynivalenol (DON) is one of the most common mycotoxins in cereal crops and their by-products, posing severe effects to the health of human and animals. However, DON-induced food contamination varies from different regions. Therefore, it is urgent to summarize a review to update information about DON exposure in various food commodities worldwide for future research and regulation. Scope and approach In this review, we summarize some typical surveys on the occurrence of DON in food raw materials and food production on human DON exposure around the world. In addition, we conclude the findings regarding masked DON in some food and discuss the daily intakes of DON in food from different regions. Key finding and conclusion DON contamination in food is a serious problem worldwide. Infants and children are susceptible to the high risk of DON exposure, which is harmful to their growth and development. Otherwise, masked DON also represents potential health risks to the population. Last but not least, the study further emphasizes strict and food security policies are needed all over the world. Highlights • DON presented high occurrence and exposure in food worldwide. • Masked DON also represented potential health risks to the population. • Infants and children were susceptible to the high risk of DON exposure. • Strict and food security policies are needed for each country all over the world. [ABSTRACT FROM AUTHOR]

Abstract Background Aflatoxins are strong cancerogenic compounds predominantly produced by certain strains of the Aspergillus genus. Due to their extreme stability in different conditions, it is very difficult to remove them completely in human diet and animal feeds. In this way aflatoxins are triggering numerous healthy problems (such as liver cancer) and thus becoming a huge burden to the hygiene system and food industry worldwide. Scope and approach Therefore, seeking for an effective technique to degrade aflatoxins to a threshold level has been a “hot-topic” among researchers. Traditional methods to detoxify aflatoxins include physical and chemical treatments, such as an extrusion cooking process and ammoniation, respectively. Meanwhile a bio-degradation by microorganisms gains its popularity due to its friendliness to both environment and body health. Natural phytochemicals (plant extracts) which have great capability to remove aflatoxins without causing any damage on human and animals come out as an improvement. Key findings and conclusion However, a fully and systematically discussion of the methods of detoxification for aflatoxins is still not available. Therefore, in the present review we briefly enumerate several traditional strategies, update newly methods, particularly the potential use of natural phytochemicals, and discuss some mechanisms during the detoxification period, summarizing merits and demerits of these methods. We suggest that this important information and our humble opinions could help researchers to understand the degradation of methods for aflatoxins. Graphical abstract Image 1 Highlights • Aflatoxin B 1 is classified as a Group I carcinogen by IARC. • Aflatoxin contamination is a great threat to human and animal health. • Physical, chemical and biological degradations are three major ways. • Phytochemicals have also been regarded as a promising approach. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON, vomitoxin) is the most frequent mycotoxin in grains and grain products. DON contamination in fodder and food is a serious threat for health, since it impairs the immune and gastrointestinal systems of both human and animals. Gut microbiota seems to play a more and more important part in human and animals' health according to related researches. Previous studies implied some associations among gut microbiota, DON and immune system. For example, DON affects immune system as well as the composition and abundance of gut microbiota, and the latter influences immune system as well. In the present short review, we not only provide the available information about the toxic consequences of DON-induced immunotoxicity on different animals and cell lines and discuss its main possible molecule mechanisms, but also summarize research results concerning the role of gut microbiota in DON-induced immunotoxicity and gender differences, with the aim to find some potential therapeutic strategies to tackle DON-induced immunotoxicity. [ABSTRACT FROM AUTHOR]

The beneficial effects of red wine against cardiovascular disease are associated with the abundant antioxidant polyphenols such as procyanidins. Recently, procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins showed strong antioxidant activities in vitro, have been isolated and identified in our laboratory. The aim of present study was to investigate the anti-atherosclerotic effects of LPPC on atherosclerosis and hyperlipidemia in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet (HFD, 21% fat, 0.15% cholesterol) for 24 weeks. The results showed that LPPC intervention alleviated atherosclerosis, fat accumulation and hyperlipidemia in ApoE KO mice. Furthermore, real-time RT-PCR results showed that LPPC can regulate several key genes involved in hepatic lipid homeostasis, such as increasing mRNA levels of farnesoid X receptor (FXR) and small heterodimer partner (SHP) which emerge as key regulators of lipid homeostasis at the transcriptional level, decreasing mRNA levels of 3-hydroxy-3-Methylglutaryl (HMG)-CoA reductase which mediates cholestrol biosynthesis, and up-regulating the mRNA expressions of ATP-binding cassette transporter-1 (ABCA1) which modulates cholesterol efflux. Thus, these results elucidated that LPPC could alleviate the lipid disorder especially hypercholesteromia and ameliorate atherosclerosis in ApoE-KO mice fed a WTD via regulating gene expression involved in hepatic lipid homeostasis effectively. [ABSTRACT FROM AUTHOR]

7, 8-Dihydroxyflavone, as a high-affinity tropomyosin-receptor-kinase B agonist, can mimic the physiological actions of brain-derived neurotrophic factor and exert a variety of neurological actions in numerous models including Parkinsońs disease, depression, learning and memory. Nonetheless, a limited number of studies have been focused on its metabolism in mammal and no methodology has been reported for the determination of 7, 8-DHF and its metabolites. Herein, we developed a rapid, sensitive and accurate method using high performance liquid chromatography–tandem mass spectroscopy for the determination of 7, 8-DHF and its metabolites in monkey plasma. The lower limits of quantification for analytes were 0.4–2.0 ng mL −1 . The intra-day and inter-day precisions (relative standard deviation, %) of analytes were within 11.83%, and the accuracy (relative error, %) ranged from −6.86 to 14.00%. The mean extraction recoveries for analytes were more than 89.14%. This validated method was successfully applied to the metabolic profile study of 7, 8-DHF in monkey plasma. The results indicated that 7, 8-DHF undergoes methylation, glucuronidation and/or sulfation, and the conjugated forms are the main metabolites in monkey plasma. We further demonstrated that methylated 7, 8-DHF can be also conjugated with glucuronidation/sulfation, and the methylation occurs mainly in the 8 position. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have emerged as important molecules in cardiovascular function. Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase is the major source of ROS in phagocytic and vascular cells. Several lines of evidence indicate that quercetin contributes to protecting against atherosclerosis. Herein, we investigated the effect of quercetin on alleviating atherosclerosis by regulating NADPH oxidase subunits expression in vivo, and explored the mechanism of quercetin suppressing the ROS overproduction stimulated by ox-LDL in mouse peritoneal macrophages (MPMs). Model ApoE KO mice were fed with either a normal chow diet or a high fat diet (HFD) supplemented with or without dosed quercetin for 24 weeks. Quercetin significantly reduced the atherosclerotic plaque area, alleviated the systemic oxidative stress, and suppressed aortic p47phox, p67phox expressions but partially reversed the NOX4 expression as compared to those in the HFD group. In vitro, quercetin effectively inhibited the ox-LDL induced ROS formation in MPMs, and blocked the vital step in activation of NADPH oxidase — membrane translocation of p47phox. Our findings suggest that regular consumption of dietary quercetin plays a role in preventing atherosclerosis giving its evident regulatory effect on subunits of NADPH oxidase. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a toxic fungal secondary metabolite produced by molds of the Fusarium genus, and it is known to cause a spectrum of diseases both in humans and animals, such as emesis, diarrhea, anorexia, immunotoxicity, hematological disorders, impairment of maternal reproduction, and fetal development. The recently revealed teratogenic potential of DON has received much attention. In various animal models, it has been shown that DON led to skeletal deformities of the fetus. However, the underlying mechanisms are not yet fully understood, and toxicological data are also scarce. Several animal research studies highlight the potential link between morphological abnormalities and changes of autophagy in the reproductive system. Because autophagy is involved in fetal development, maintenance of placental function, and bone remodeling, this mechanism has become a high priority for future research. The general aim of the present review is to deliver a comprehensive overview of the current state of knowledge of DON-induced reproductive toxicity in different animal models and to provide some prospective ideas for further research. The focus of the current review is to summarize toxic and negative effects of DON exposure on the reproductive system and the potential underlying molecular mechanisms in various animal models. [ABSTRACT FROM AUTHOR]

[Display omitted] • Exposure to perchlorate, nitrate, and thiocyanate was ubiquitous in the Chinese adult population. • Urinary perchlorate, nitrate, and thiocyanate were associated with significant changes in thyroid function markers. • Co-exposure to three goitrogenic anions was inversely associated with serum FT4, TT4, and FT3. Evidence on environmental exposure to perchlorate, nitrate, and thiocyanate, three thyroidal sodium iodine symporter (NIS) inhibitors, and thyroid function in the Chinese population remains limited. To investigate the associations of environmental exposure to perchlorate, nitrate, and thiocyanate with markers of thyroid function in Chinese adults. A total of 2441 non-pregnant adults (mean age 50.4 years and 39.1% male) with a median urinary iodine of 180.1 μg/L from four communities in Shenzhen were included in this cross-sectional study. Urinary perchlorate, nitrate, thiocyanate, and thyroid profiles, including serum free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH), were measured. Generalized linear model was applied to investigate the single-analyte associations. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to examine the association between the co-occurrence of three anions and thyroid profile. The median levels of urinary perchlorate, nitrate, and thiocyanate were 5.8 μg/g, 76.4 mg/g, and 274.1 μg/g, respectively. After adjusting for confounders, higher urinary perchlorate was associated with lower serum FT4, TT4, and TT3, and higher serum FT3 and TSH (all P < 0.05). Comparing extreme tertiles, subjects in the highest nitrate tertile had marginally elevated TT3 (β : 0.02, 95% CI: 0.00–0.04). Each 1-unit increase in log-transformed urinary thiocyanate was associated with a 0.04 (95% CI: 0.02–0.06) pmol/L decrease in serum FT3. The WQS indices were inversely associated with serum FT4, TT4, and FT3 (all P < 0.05). In the BKMR model, the mixture of three anions was inversely associated with serum FT4, TT4, and FT3. Our study provides evidence that individual and combined environmental exposure to perchlorate, nitrate, and thiocyanate are associated with significant changes in thyroid function markers in the Chinese population with adequate iodine intake. [ABSTRACT FROM AUTHOR]

Whey protein has been reported to be an impactful dietary supplement to ameliorate skeletal muscle aging for a long time. However, whether whey protein could contribute to muscle aging amelioration by post-transcriptional modulation remains unclear. In this study, 19-month-old mice orally received whey protein supplementation (1.0 g/kg/bw/d, whey protein group) or deionized water (the control group) for 3 months. Differentially expressed ncRNAs and mRNAs in quadriceps were identified by RNA-seq. Construction of non-coding RNAs (ncRNAs)-associated competing endogenous RNA (ceRNA) networks as well as GO and KEGG enrichment analyses were also carried out subsequently. Meanwhile, ultrasound measurement, H&E staining, myofiber cross-sectional area measurement, western blotting and RT-qPCR were performed in the quadriceps to evaluate muscle status and verify the RNA-seq data. Whey protein supplementation for 3 months increased quadriceps-body weight ratio and improved the histological as well as ultrasonographic characteristics of aging in muscle. Moreover, the protein expression levels of Myog, Myf4, Myf5 and MyoD1 were all significantly elevated in quadriceps. The expression of 90 lncRNAs, 334 mRNAs, six circRNAs and 52 miRNAs were significantly up or down-regulated in quadriceps after whey protein supplementation. Furthermore, ncRNAs-associated networks and GO and KEGG enrichment analyses revealed whey protein may influence muscle aging process through selected ncRNAs-associated ceRNA networks. Therefore, post-transcriptional modulation could be a potential crucial way to ameliorate skeletal muscle aging after whey protein supplementation. The selected ncRNAs-associated ceRNA networks may provide new insight for the underlying mechanism and profound therapeutic target for skeletal muscle aging. [ABSTRACT FROM AUTHOR]

[Display omitted] • Urinary perchlorate and thiocyanate were positively associated with central thyroid hormones sensitivity. • Co-occurrence of perchlorate, nitrate, and thiocyanate was positively associated with central thyroid hormones sensitivity. • The positive association of co-exposure of three anions with central thyroid hormones sensitivity was mostly attributed to thiocyanate. Perchlorate, nitrate, and thiocyanate are three well-known sodium iodine symporter inhibitors, however, associations of their individual and concurrent exposure with central thyroid hormones sensitivity remain unclear. To investigate the associations of urinary perchlorate, nitrate, thiocyanate, and their co-occurrence with central thyroid hormones sensitivity among US general adults. A total of 7598 non-pregnant adults (weighted mean age 45.9 years and 52.9% men) from National Health and Nutritional Examination Survey 2007–2012 were included in this cross-sectional study. Central sensitivity to thyroid hormones was estimated with the Parametric Thyroid Feedback Quantile-based Index (PTFQI). Ordinary least-squares regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were performed to examine the associations of three anions and their co-occurrence with PTFQI. The weighted mean values of urinary perchlorate, nitrate, thiocyanate, and perchlorate equivalent concentration (PEC) were 5.48 μg/L, 57.59 mg/L, 2.65 mg/L, and 539.8 μg/L, respectively. Compared with the lowest quartile, the least-square means difference (LSMD) of PTFQI was −0.0516 (LSMD ± SE: −0.0516 ± 0.0185, P < 0.01) in the highest perchlorate quartile. On average, PTFQI decreased by 0.0793 (LSMD ± SE: −0.0793 ± 0.0205, P < 0.001) between the highest and lowest thiocyanate quartile. Compared with those in the lowest quartile, participants in the highest PEC quartile had significantly decreased PTFQI levels (LSMD ± SE: −0.0862 ± 0.0188, P < 0.001). The WQS of three goitrogens, was inversely associated with PTFQI (β : −0.051, 95% CI: −0.068, −0.034). In BKMR model, PTFQI significantly decreased when the levels of three anions were at or above their 60th percentiles compared to the median values. Higher levels of urinary perchlorate, thiocyanate, and co-occurrence of three goitrogens were associated with increased central thyroid hormones sensitivity among US general adults. Further studies are warranted to replicate our results and elucidate the underlying causative mechanistic links. [ABSTRACT FROM AUTHOR]

Highlights: [•] QCT-induced oxidative stress led to DNA damage, inflammation and apoptosis. [•] Persistent QCT exposure inhibited Nrf2/HO-1 pathway expression. [•] QCT-induced Nrf2/HO-1 pathway suppression aggravates hepatocyte damage of SD rats. [Copyright &y& Elsevier]

Abstract: Emerging evidence has demonstrated that chronic ethanol exposure induces iron overload, enhancing ethanol-mediated liver damage. The purpose of this study was to explore the effects of the naturally occurring compound quercetin on ethanol-induced iron overload and liver damage, focusing on the signaling pathway of the iron regulatory hormone hepcidin. Adult male C57BL/6J mice were pair-fed with isocaloric-Lieber De Carli diets containing ethanol (accounting for 30% of total calories) and/or carbonyl iron (0.2%) and treated with quecertin (100 mg/kg body weight) for 15 weeks. Mouse primary hepatocytes were incubated with ethanol (100 mM) and quercetin (100 μM) for 24 h. Mice exposed to either ethanol or iron presented significant fatty infiltration and iron deposition in the liver; these symptoms were exacerbated in mice cotreated with ethanol and iron. Quercetin attenuated the abnormity induced by ethanol and/or iron. Ethanol suppressed BMP6 and intranuclear SMAD4 as well as decreased hepcidin expression. These effects were partially alleviated by quercetin supplementation in mice and hepatocytes. Importantly, ethanol caused suppression of SMAD4 binding to the HAMP promoter and of hepcidin messenger RNA expression. These effects were exacerbated by anti-BMP6 antibody and partially alleviated by quercetin or human recombinant BMP6 in cultured hepatocytes. In contrast, co-treatment with iron and ethanol, especially exposure of iron alone, activated BMP6/SMAD4 pathway and up-regulated hepcidin expression, which was also normalized by quercetin in vivo. Quercetin prevented ethanol-induced hepatic iron overload different from what carbonyl iron diet elicited in the mechanism, by regulating hepcidin expression via the BMP6/SMAD4 signaling pathway. [Copyright &y& Elsevier]

Highlights: [•] Quercetin counteracted ethanol-derived hepatic oxidative stress and liver damage. [•] Quercetin alleviated ethanol-induced liver iron overload and “free” iron disorder. [•] Quercetin inhibited ethanol-stimulated DMT1, ZIP14 and TRPML1 responsible for “free” iron uptake and release. [•] In addition, quercetin suppressed ethanol-stimulated TfR1 and Ft light chain expression. [ABSTRACT FROM AUTHOR]

Highlights: [•] DON induced genotoxicity in human lymphocytes. [•] DON evoked oxidative stress to deplete antioxidase. [•] Depletion of antioxidase reduced ability of DNA repair. [•] Oxidative stress also up-regulated or inhibited expression of HO-1 in 6 or 24h. [Copyright &y& Elsevier]