Search

Targeting the gut microbiota may be an emerging strategy for the prevention and treatment of Alzheimer's disease (AD). Macro-molecular yeast β-glucan (BG), derived from the yeast of Saccharomyces cerevisiae, regulates the gut microbiota. This study aimed to investigate the effect and mechanism of long-term BG in high-fat diet (HFD)-induced AD-like pathologies from the perspective of the gut microbiota. Here, we found that 80 weeks of BG treatment ameliorated HFD-induced cognitive dysfunction in rats. In the hippocampus, BG alleviated HFD-induced the activation of astrocytes, microglia, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway, and AD-like pathologies. BG modulated gut dysbiosis through increasing the levels of beneficial bacteria and short-chain fatty acids (SCFAs). BG also attenuated HFD-induced gut barrier impairment. Correlation analysis revealed a close relationship among microbiota, SCFAs, and AD-like pathologies. Furthermore, the fecal microbiota of BG-treated rats and SCFAs treatment mitigated AD-like pathologies via the NLRP3 inflammasome pathway in HFD-fed aged rats. These results suggested that long-term BG promotes the production of SCFAs derived from gut microbiota, which further inhibits NLRP3 inflammasome-mediated neuroinflammation, thereby alleviating HFD-induced AD-like pathologies in rats. BG may become a new strategy for targeting neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: 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., Design: Prospective cohort study., Setting and Participants: A total of 333,865 adults (mean age of 56 years) from the UK Biobank were analyzed., Methods: 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., Results: 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)., Conclusions and Implications: 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., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Lifestyle management is a fundamental aspect of diabetes care to prevent cardiovascular disease (CVD); however, the underlying metabolic mechanism is not well established. We aimed to identify metabolites associated with different lifestyle factors, and estimate their mediating roles between lifestyle and CVD risk among people with diabetes., Methods: Lifestyle and metabolomic data were available for 5072 participants with diabetes who were free of CVD at baseline in the UK Biobank. The healthy level of 5 lifestyle factors was defined as non-central obesity, non-current smoking, moderate alcohol intake, physically active, and healthy diet. A total of 44 biomarkers across 7 metabolic pathways including lipoprotein particles, fatty acids, amino acids, fluid balance, inflammation, ketone bodies, and glycolysis were quantified by nuclear magnetic resonance (NMR) spectroscopy., Results: All 44 assayed metabolites were significantly associated with at least one lifestyle factor. Approximately half of metabolites, which were mostly lipoprotein particles and fatty acids, showed a mediating effect between at least one lifestyle factor and CVD risk. NMR metabolites jointly mediated 43.4%, 30.0%, 16.8%, 43.4%, and 65.5% of the association of non-central obesity, non-current smoking, moderate alcohol intake, physically active, and healthy diet with lower CVD risk, respectively. In general, though metabolites that significantly associated with lifestyle were mostly different across the 5 lifestyle factors, the pattern of association was consistent between fatty acids and all 5 lifestyle factors. Further, fatty acids showed significant mediating effects in the association between all 5 lifestyle factors and CVD risk with mediation proportion ranging from 12.2% to 26.8%., Conclusions: There were large-scale differences in circulating NMR metabolites between individuals with diabetes who adhered to a healthy lifestyle and those did not. Differences in metabolites, especial fatty acids, could partially explain the association between adherence to multiple healthy lifestyle and lower CVD risk among people with diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (Copyright © 2022 American Society for Nutrition.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (Copyright © 2022 American Society for Nutrition.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Persistent organic pollutants (POPs) remain a major point of concern worldwide, and surveillance monitoring of these contaminants presents a significant challenge. Here, we conducted an assessment of combined exposure to multiple POPs components [10 perfluoroalkyl acids (PFAAs), seven polybrominated diphenyl ethers (PBDEs), six polychlorinated biphenyls (PCBs) and 29 dioxin-like compounds (DLCs)] in relation to gestational diabetes mellitus (GDM) risk, and determined the identification and prioritization of potent components in these POPs mixtures. The results indicated a significant mixture effect and the combined exposure index estimated from multiple POPs components was associated with GDM and glucose homeostasis (P < 0.001). Based on the mixture effects on GDM, the procedure of prioritization identified DLCs as the components of the greatest concern, although at the lowest body burden in the population compared with PBDEs, PFAAs, and PCBs. For glucose homeostasis, BDE-153 was the chemical of top-ranked priority of concern. The final effect-based prioritized list of POPs was DLCs > PBDEs >PFAAs > PCBs. This prioritization is important for developing a more cost-effective regulation framework focusing on the POPs components of the greatest concern to human health., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Obesity is now a worldwide disease and is mainly attributable to increased body fat deposition. In a growing number of epidemiological studies, lutein has been revealed to have different degrees of anti-obesity properties, but the potential underlying mechanisms that have been reported are limited. Therefore, we aimed to clarify the protective effects of lutein against excessive lipid accumulation, and we explored the role of SIRT1 and SIRT1-mediated pathways both in abdominal adipose tissue and mature 3T3-L1 cells during lutein administration., Methods: In our design, male Sprague-Dawley rats were fed either control or high-fat diets with or without 25 mg/kg·bw/day lutein for 5 weeks. Additionally, differentiated 3T3-L1 cells were incubated with 40 μM lutein or 10 μM Ex527 for 24 h., Results: Lutein supplementation decreased the body weight, abdominal fat index ratio, frequency and mean area of larger adipocytes in HE staining induced by the high-fat diet and then activated the expression of SIRT1 and thus upregulated FoxO1, ATGL, and HSL expression and downregulated SREBP-1, FAS, and ACC expression both in abdominal adipose tissue and differentiated 3T3-L1 cells. However, coincubation with Ex527 and lutein suppressed the activation of SIRT1 and reversed the expression of FoxO1, ATGL, HSL, SREBP-1, FAS, and ACC in comparison to those in the Lut group., Conclusions: Overall, we suggest that the effects of lutein on attenuating excessive lipid accumulation are dependent on the SIRT1-mediated pathway in vivo and in vitro, which indicates that lutein administration may be a potential strategy for preventing excessive lipid accumulation and obesity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The long-term associations between the consumption of sugar-sweetened beverages (SSBs) and low-calorie sweetened beverages (LCSBs) with cardiovascular diseases (CVDs) remains inconsistent. To synthesize the evidence, we conducted a meta-analysis of prospective cohort studies published up to 1 December, 2019 on the associations between SSB and LCSB intake and the risk of CVD incidence and mortality. Out of 5301 articles retrieved from our literature search, 11 articles evaluating the consumption of SSBs (16,915 incident CVD cases, 18,042 CVD deaths) and 8 articles evaluating the consumption of LCSBs (18,077 incident CVD cases, 14,114 CVD deaths) were included in the meta-analysis. A 1 serving/d increment of SSBs was associated with an 8% (RR: 1.08; 95% CI: 1.02, 1.14, I2 = 43.0%) and 8% (RR: 1.08; 95% CI: 1.04, 1.13, I2 = 40.6%) higher risk of CVD incidence and CVD mortality, respectively. A 1 serving/d increment of LCSBs was associated with a 7% (RR: 1.07; 95% CI: 1.05, 1.10, I2 = 0.0%) higher risk of CVD incidence. The association between LCSBs and CVD mortality appeared to be nonlinear (P = 0.003 for nonlinearity) with significant associations observed at high intake levels (>2 servings/d). Under an assumption of causality, the consumption of SSBs may be linked to 9.3% (95% CI: 6.6%, 11.9%) of predicted CVD incidence in the USA from 2015 to 2025, among men and nonpregnant women, who were aged 40-79 y in 2015-2016. The habitual consumption of SSBs was associated with a higher risk of CVD morbidity and mortality in a dose-response manner. LCSBs were also associated with a higher risk of these outcomes, however, the interpretation of these findings may be complicated by reverse causation and residual confounding., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

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., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and all authors approved this manuscript. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2020. Published by Elsevier B.V.)

Background & Aims: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Emerging findings have raised concerns about significant associations between excessive copper (Cu) and abnormal glucose metabolism. Nevertheless, related researches on the relationship of Cu concentration and gestational diabetes mellitus (GDM) are limited. The objective of this study was to determine whether plasma Cu concentration is associated with GDM., Methods: A case-control study of 248 cases of GDM and 248 age-, parity- and gestational age-matched controls was conducted in Wuhan, China between August 2012 and April 2015. Fasting blood samples of participants were collected at the time of GDM screening (≥24 weeks of gestation). Plasma Cu concentrations were detected by inductively coupled plasma mass spectrometry. The strength of the association of plasma Cu with GDM odds was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs) from conditional logistic regression. Partial Spearman or Pearson correlation coefficients were calculated to estimate the interrelationship between plasma Cu and the risk factors of GDM., Results: Plasma Cu concentrations in the GDM group (mean ± SD: 1960.24 ± 391.98 μg/L) were higher than in the control group (mean ± SD: 1842.43 ± 387.09 μg/L) (P = 0.001). After adjustment for possible confounders, the ORs (95% CIs) of GDM across increasing quartiles of plasma Cu levels were 1.00 (referent), 1.79 (0.90-3.55), 2.72 (1.35-5.48) and 2.91 (1.48-5.75), respectively; the OR (95% CI) of GDM was 1.33 (1.06-1.67) for each standard deviation increment of plasma Cu. Moreover, Cu concentrations were positively associated with fasting plasma glucose, 1-h post-glucose load and 2-h post-glucose load (all P < 0.05)., Conclusions: The present study indicated a significantly increased odds of GDM in association with higher concentrations of plasma Cu. Prospective cohort studies in other populations are needed to confirm our findings., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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.

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 had GDM screened during 24-32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted in Wuhan, 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. This trial was registered at www.clinicaltrials.gov as NCT03415295.

The cause of late onset Parkinson's disease (PD) remains unknown. Evidence suggested that lifelong exposure to pesticides might contribute to the development of neurodegenerative diseases, but the results were controversial. Relevant studies were identified by searching PubMed and Web of Science through September 2017. We included cohort and case-control studies reporting relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) of three or more categories of pesticide exposure and PD. Ten articles with 13 reports (3 for cumulative exposure, 10 for duration exposure) were included. A nonlinearity association was seen between duration exposure and PD risk (P = 0.01 for nonlinearity). The summary ORs of developing PD for 5 and 10 years of duration exposure were 1.05 (95% CI: 1.02-1.09) and 1.11 (95% CI: 1.05-1.18), respectively. Sensitivity analyses with different effect models yielded similar results, and omission of any single study did not change the results. The 5 and 10 years of duration pesticide exposure were associated with a 5% and 11% augment in the risk of PD. Further high-quality cohort studies were required to validate a causal relationship., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin. ACR exposure at 10 mg/kg/d for 7 weeks caused slight gait abnormality and spatial memory deficits, which was associated with an activation of glial cells, a reduction of phosphorylated cAMP response elements binding protein (P-CREB) and an aggregation of hyperphosphorylated tau including p-tau (Ser 262 ), AT8 (p-tau Ser 202 /Thr 205 ) and PHF1 (p-tau Ser 396/404 ) in the hippocampus and cortex. ACR markedly regulate the expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-5 (cdk5) to accelerate tau hyperphosphorylation. ACR inhibited the protein phosphatase 2A (PP2A) and lysosomal protease cathepsin D to decrease the p-tau dephosphorylation and degradation. The P-CREB and brain derived neurotrophic factor (BDNF) were significantly decreased by ACR. The upstream signalings of P-CREB, extracellular signal-related kinase (ERK) and Akt were markedly inhibited. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2α (eIF2α) - activating transcription factor 4 (ATF4) signaling which negatively regulate memory processes by suppressing CREB was activated by ACR. Curcumin alleviated ACR-induced spatial memory impairment through reversing tau abnormalities and P-CREB reduction in the hippocampus. These results offered deeper insight into the mechanisms of and presented a potential new treatment for ACR-induced neurotoxicity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The association of trimethylamine- N -oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent. Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms. Design: This was an age- and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped. Results: Medians (IQRs) of plasma TMAO concentration were 1.47 μmol/L (0.81-2.20 μmol/L) for controls and 1.77 μmol/L (1.09-2.80 μmol/L) for type 2 diabetes cases. From the lowest to the highest quartiles of plasma TMAO, the multivariable adjusted ORs of type 2 diabetes were 1.00 (reference), 1.38 (95% CI: 1.08, 1.77), 1.64 (95% CI: 1.28, 2.09), and 2.55 (95% CI: 1.99, 3.28) ( P -trend < 0.001); each SD of ln-transformed plasma TMAO was associated with a 38% (95% CI: 26%, 51%) increment in ORs of type 2 diabetes. The FMO3 rs2266782 polymorphism was not associated with type 2 diabetes. The positive association between plasma TMAO and type 2 diabetes was consistent in each rs2266782 genotype group, and no significant interaction was observed ( P = 0.093). Conclusions: Our results suggested that higher plasma TMAO was associated with increased odds of newly diagnosed type 2 diabetes and that this association was not modified by the FMO3 rs2266782 polymorphism. This study was registered at clinicaltrials.gov as NCT03130894., (© 2017 American Society for Nutrition.)

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 0.4-2.0ngmL -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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aging is a principal risk factor for neurodegenerative diseases and especially shares similar pathologic mechanisms to Alzheimer's disease (AD). Amyloid-β (Aβ) plaques deposition and neurofibrillary tangles (NFTs) are the prominent age-dependent pathologies implicated in the cognitive deficits. Accumulation of mis-folded proteins in the endoplasmic reticulum triggers a cellular stress response called the unfolded protein response (UPR), the activation of which is increased in AD patients. However, the UPR relates to the pathological hallmarks of aging is still elusive. In this study, we report that long-term supplement of α-linolenic acid (ALA), starting before the onset of disease symptoms (6month-old), prevents the age-related memory deficits during natural aging. The amelioration of the memory impairment is associated with a decrease in UPR related markers [glucose regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), eukaryotic Initiation Factor 2α (eIF2α)]. ALA suppressed the PERK/eIF2α signaling, which may be responsible for multifaceted memory-deteriorating and neurodegenerative mechanisms, including inhibition of Aβ production by suppressing β-site APP-cleaving enzyme 1 (BACE1) expression, enhancement of cAMP response element binding protein (CREB) function via down-regulating activating transcription factor 4 (ATF4), and suppression of Tau phosphorylation by inhibiting glycogen synthase kinase 3β (GSK-3β) pathway. Taken together, our findings provide new insights into the link between ALA and PERK/eIF2α signaling, which could contribute to a better understanding of an ALA-mediated protective effect in aging-associated neuropathology., (Copyright © 2015 Elsevier Inc. All rights reserved.)

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) has been broadly used to treat dysentery and promote animal growth in food producing animals. However, its potential toxicity could not been neglected as parts of safety assessment according to the acceptable guidelines for QCT administration. In this study, the immunotoxicity of QCT was investigated in male Sprague-Dawley (SD) rats following a 28-day oral exposure at doses of 0, 50, 800, and 2400 mg/kg/day. The food consumption, body weight gain and relative spleen weight were significantly decreased by QCT in a dose-dependent manner. Treatment of rats with QCT also notably suppressed the T-cell proliferation and natural killer (NK) cell activity, accompanied by intracellular reactive oxygen species (ROS) accumulation, antioxidant system inhibition and DNA damage enhancement. Thus, the primary finding of this study is that QCT exposure (2400 mg/kg/day) could cause immunotoxicity in SD rats due to ROS mediated oxidative stress and DNA damage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Chronic activation of brain-derived neurotrophic factor (BDNF) receptor TrkB is a potential method to prevent development of obesity, but the short half-life and nonbioavailable nature of BDNF hampers validation of the hypothesis. We report here that activation of muscular TrkB by the BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is sufficient to protect the development of diet-induced obesity in female mice. Using in vitro and in vivo models, we found that 7,8-DHF treatment enhanced the expression of uncoupling protein 1 (UCP1) and AMP-activated protein kinase (AMPK) activity in skeletal muscle, which resulted in increased systemic energy expenditure, reduced adiposity, and improved insulin sensitivity in female mice fed a high-fat diet. This antiobesity activity of 7,8-DHF is muscular TrkB-dependent as 7,8-DHF cannot mitigate diet-induced obesity in female muscle-specific TrkB knockout mice. Hence, our data reveal that chronic activation of muscular TrkB is useful in alleviating obesity and its complications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Epidemiologic studies have shown inverse associations between nut consumption and diabetes, cardiovascular disease (CVD), and all-cause mortality, but results have not been consistent., Objective: We assessed the relation between nut intake and incidence of type 2 diabetes, CVD, and all-cause mortality., Design: We searched PubMed and EMBASE for all prospective cohort studies published up to March 2013 with RRs and 95% CIs for outcomes of interest. A random-effects model was used to pool risk estimates across studies., Results: In 31 reports from 18 prospective studies, there were 12,655 type 2 diabetes, 8862 CVD, 6623 ischemic heart disease (IHD), 6487 stroke, and 48,818 mortality cases. The RR for each incremental serving per day of nut intake was 0.80 (95% CI: 0.69, 0.94) for type 2 diabetes without adjustment for body mass index; with adjustment, the association was attenuated [RR: 1.03; 95% CI: 0.91, 1.16; NS]. In the multivariable-adjusted model, pooled RRs (95% CIs) for each serving per day of nut consumption were 0.72 (0.64, 0.81) for IHD, 0.71 (0.59, 0.85) for CVD, and 0.83 (0.76, 0.91) for all-cause mortality. Pooled RRs (95% CIs) for the comparison of extreme quantiles of nut intake were 1.00 (0.84, 1.19; NS) for type 2 diabetes, 0.66 (0.55, 0.78) for IHD, 0.70 (0.60, 0.81) for CVD, 0.91 (0.81, 1.02; NS) for stroke, and 0.85 (0.79, 0.91) for all-cause mortality., Conclusions: Our meta-analysis indicates that nut intake is inversely associated with IHD, overall CVD, and all-cause mortality but not significantly associated with diabetes and stroke. The inverse association between the consumption of nuts and diabetes was attenuated after adjustment for body mass index. These findings support recommendations to include nuts as part of a healthy dietary pattern for the prevention of chronic diseases., (© 2014 American Society for Nutrition.)

Nanobiotechnology has been recently viewed as a promising strategy to improve therapy efficacy by promoting the accumulation of hydrophobic bioactive compounds in tissues. The aim of present study was to formulate a novel quercetin-loaded cationic nanostructured lipid carriers (QR-CNLC) and to evaluate its biodistribution in vivo after oral administration. QR-CNLC were prepared by emulsifying at high temperature and subsequent solidifying at low temperature using various functional ingredients, and its characteristics, including physical index, release profile in vitro, and tissue distribution in vivo, were investigated. The results demonstrated that QR-CNLC exhibited an average particle size 126.6 nm, a zeta potential of 40.5 mV and 89.3% entrapment efficiency. QR-CNLC performed slower release compared with quercetin solution in vitro. QR-CNLC showed higher AUC (area under tissue concentration-time curve) value and higher Cmax value in lung, liver and kidney compared with control group. The value of relative intake rate (re) for lung, liver and kidney was 1.57, 1.51 and 1.68, respectively, which revealed that quercetin can be significantly accumulated in lung, kidney and liver after oral administration of QR-CNLC compared with quercetin suspension. In conclusion, cationic nanostructured lipid carriers may be an attractive nanocarrier system for oral delivery of hydrophobic functional components., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The association between obstructive sleep apnea (OSA) and the incidence of cardiovascular disease (CVD) has been examined in many studies. However, the findings are not entirely consistent across studies. Our goal was to evaluate the association between OSA and risk of CVD and all-cause mortality by performing a meta-analysis of prospective cohort studies., Methods: We used generalized least squares regression models to estimate the dose-response relationship. Heterogeneity, subgroup, and sensitivity analyses and publication bias were performed., Results: Twelve prospective cohort studies involving 25,760 participants were included in the meta-analysis. The overall combined relative risks for individuals with severe OSA compared with individuals with an AHI of <5 were 1.79 (95% confidence interval [CI]: 1.47 to 2.18) for CVD, 1.21 (95% CI: 0.75 to 1.96) for incident fatal and non-fatal coronary heart disease, 2.15 (95% CI: 1.42 to 3.24) for incident fatal and non-fatal stroke, and 1.92 (95% CI: 1.38 to 2.69) for deaths from all-causes. A positive association with CVD was observed for moderate OSA but not for mild OSA. The results of the dose-response relationship indicated that per 10-unit increase in the apnea-hypopnea index was associated with a 17% greater risk of CVD in the general population., Conclusions: This meta-analysis of prospective cohort studies suggests that severe OSA significantly increases CVD risk, stroke, and all-cause mortality. A positive association with CVD was observed for moderate OSA but not for mild OSA., (© 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) is a newly used veterinary drug which has been proven to promote feed efficiency and growth of animals; however, its potential toxicity can't be ignored. Therefore, the present study was aimed to investigate the nephrotoxicity of QCT and the oxidative stress induced by it. Sprague-Dawley rats (SD rats) were randomly divided into four groups with doses of 2400, 800, 50 and 0mg/kg/day with administration of QCT for 4 weeks. Results proved that QCT could induce nephrotoxicity and this phenomenon had dose dependent manner. Simultaneously, this phenomenon was accompanied by intracellular reactive oxygen species (ROS) accumulation, enhanced lipid peroxidation and inhibited antioxidant system, i.e. glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GSH). Additionally, the higher expression of Nrf2 in QCT treated groups illustrated that QCT-induced oxidative stress would be partly mitigated by the induction of phase II detoxifying enzymes via increasing Nrf2 expression., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: This systematic review and meta-analysis was conducted to estimate the effects of intravenous and nebulized magnesium sulfate on treating adults and children with acute asthma., Methods: Electronic literature search and the manual search of key respiratory journals were performed up to October 18, 2011. Randomized controlled trials were included if patients had been treated with intravenous or nebulized magnesium sulfate in combination with β2-agonists and were compared with the use of β2-agonists. Standardized mean differences (SMDs) and the relative risks (RRs) were calculated for pulmonary functions and hospital admission respectively., Results: 25 trials (16 intravenous, 9 nebulized) involving 1754 patients were included. In adults intravenous treatment was associated with a significant effect upon respiratory function (SMD, 0.30; 95% confidence interval (CI), 0.05 to 0.55; p = 0.02) but weak evidence of effect upon hospital admission (RR 0.86,95% CI 0.73 to 1.01; p = 0.06) in adults, and in children with significant effects upon both respiratory function (SMD, 1.94; 95% CI, 0.80 to 3.08; p = 0.0008) and hospital admission (RR, 0.70; 95% CI, 0.54 to 0.91; p = 0.008). Nebulized treatment was associated with significant effects upon respiratory function (SMD, 0.23; 95% CI, 0.06 to 0.41; p = 0.009) and hospital admission (RR, 0.63; 95% CI, 0.43 to 0.92; p = 0.02) in adults., Conclusion: The use of intravenous magnesium sulfate, in addition to β2-agonists and systemic steroids, in the treatment of acute asthma appears to produce benefits with respect to improve pulmonary function and reduce the number of hospital admissions for children, and only improve pulmonary function for adults. However, the use of nebulized magnesium sulfate just appears to produce benefits for adults., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments in cognitively impaired aged rats. Based on Morris water maze performance compared with young female rats, aged unimpaired (AU) and aged impaired (AI) rats were chosen from aged female rats. LSPC supplementation (50, 100 mg/kg BW, p.o.) for 7 weeks significantly improved learning and memory impairments in AI animals in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. Aged rats had significantly declined antioxidant defense capacities and significantly increased lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex than young rats. Further, AI group had higher protein oxidation level compared with AU group. LSPC (50, 100 mg/kg BW, p.o.) significantly reversed the decline of antioxidant defense capacities and significantly reduced lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex of AI rats. In addition, LSPC significantly restored acetylcholine (ACh) contents and acetylcholinesterase (AChE) activities in hippocampus and cerebral cortex of AI animals. The results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by Alzheimer's disease and aging.

Ghrelin and peptide tyrosine tyrosine (PYY) are known to affect appetite and body weight, but the acute effects of fat-rich and carbohydrate-rich meals on plasma ghrelin, PYY response, and appetite remain unclear. We hypothesized that obese individuals had impaired postprandial ghrelin and PYY response based on macronutrient content of meals, affecting appetite and energy intake. We conducted a randomized crossover trail comparing fasting ghrelin and PYY concentrations, postprandial ghrelin and PYY responses, and subjective appetite in 15 obese and 12 lean Chinese young adults after they consumed isocaloric high-carbohydrate [HC; 88% energy carbohydrate, 4% energy fat, 8% energy protein] and high-fat (HF; 25% energy carbohydrate, 71% energy fat, 4% energy protein) meals. Ghrelin concentrations over time differed between HC and HF meals (P < 0.01) via repeated measures of ANOVA, with lower postprandial ghrelin suppression after HF meals, especially among obese participants. PYY response differed between meals among lean participants, with a delayed and higher postprandial PYY peak after the HF meal (P < 0.01); however, PYY response did not differ among obese participants. The incremental area under the curve of PYY was higher in lean than in obese participants after the HF meal (P < 0.01). These results suggest that impaired ghrelin response after HF meals may contribute to reduced satiety and overeating, especially among obese individuals. Whether an attenuated response of PYY in obese participants after a HF meal bears any physiological consequences warrants further study.

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 (100 mM) and quercetin (10-200 microM), 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.

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.

Background/aims: Hepatic injury induced by ischemia/reperfusion following surgery, transplantation, or circulatory shock combined with resuscitation is a major clinical problem., Methods: In this study, hypoxic and inflammatory conditions were mimicked by exposing human hepatocytes to N(2) (at 4 and 37 degrees C) or to cytokines/endotoxin to investigate the potential protective effects of heme oxygenase-1 (HO-1). Incubation of human hepatocytes with single cytokines (IFN-gamma, IL-1beta, TNF-alpha) or LPS, as well as a combination of all four stimuli (CM, cytomix) caused a time-dependent HO-1 mRNA expression over 12h and a decline by 24 h. In parallel, we observed a time-dependent membrane leakage for LDH and AST and a maximum HO-1 protein expression between 3-24 h., Results: Warm and cold hypoxia showed similar results in HO-1 mRNA and protein expression and the release of LDH and AST. CoPP, a potent HO-1 inducer, and bilirubin, a co-product of the HO-pathway, protected human hepatocytes from warm and cold hypoxia. HO-1 enzyme activity was highest during warm hypoxia, followed by cold hypoxia and CM which was confirmed by intracellular Fe(2+) formation., Conclusions: Taken together, we demonstrated, that HO-1 induction protected human hepatocytes against warm and cold hypoxia. Our results also suggest that HO-1 induction may have therapeutic potential against inflammatory insults.