Ping Yao

Huazhong University of Science and Technology, Wu-han-shih, Hubei, China

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Publications (82)226.72 Total impact

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    ABSTRACT: The prevalence of metabolic syndrome (MetS) persistently increased. Several studies have found serum creatinine (SCr) concentrations related to cardiovascular disease and type 2 diabetes. The relationship between SCr concentrations and MetS are unknown. We measured SCr concentrations and MetS in 22363 individuals (10,151 males, 12,212 females) from the Dongfeng-Tongji Cohort in Shiyan, China from 2008 to 2009. The prevalence of MetS was 30.6% in the study population. In the multivariable-adjusted logistic regression analyses, higher SCr concentrations were associated with a higher risk of MetS (P trend<0.0001). Compared with the lowest extreme quintiles, subjects with the highest quintiles had 1.34 fold risk of MetS (95% confidence interval (CI): 1.22-1.47). The SCr concentrations were also associated with the individual component of MetS. In addition, higher SCr concentrations were associated with higher risk of MetS with more components. There is a graded positive association between the SCr concentrations and MetS risk in a middle aged and older Chinese population. Higher SCr concentrations, even within normal ranges, were associated with higher risk of MetS. The SCr might be a useful indicator of MetS and its related diseases. Copyright © 2014. Published by Elsevier B.V.
    12/2014;
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    ABSTRACT: To investigate the effect of passive smoking on the changes in mean platelet volume (MPV) in healthy adults. Participants (N = 17,825) were drawn from the Dongfeng-Tongji cohort. Multiple logistic regression analysis was used to examine relationships between MPV and selected variables among subgroups of MPV clarified by the MPV reference range for Chinese adults. Female never smokers exposed to passive smoke ≥ 60 minutes every day (OR: 1.471, 95%CI: 1.147-1.886) or ≥ 30 years had a higher risk of having low MPV (OR: 1.260, 95%CI: 1.004-1.583). Certain duration of passive smoke exposure (≥ 60 minutes/day or ≥ 30 years) was associated with higher risk of having low MPV in female never smokers.
    American journal of health behavior 07/2014; 38(4):519-28. · 1.31 Impact Factor
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    ABSTRACT: Leucine, a branched-chain amino acid, has been shown to promote glucose uptake and increase insulin sensitivity in skeletal muscle, but the exact mechanism remains unestablished. We addressed this issue in cultured skeletal muscle cells in this study. Our results showed that leucine alone did not have an effect on glucose uptake or phosphorylation of protein kinase B (AKT), but facilitated the insulin-induced glucose uptake and AKT phosphorylation. The insulin-stimulated glucose uptake and AKT phosphorylation were inhibited by the phosphatidylinositol 3-kinase inhibitor, wortmannin, but the inhibition was partially reversed by leucine. The inhibitor of mammalian target of rapamycin complex 1 (mTORC1), rapamycin, had no effect on the insulin-stimulated glucose uptake, but eliminated the facilitating effect of leucine in the insulin-stimulated glucose uptake and AKT phosphorylation. In addition, leucine facilitation of the insulin-induced AKT phosphorylation was neutralized by knocking down the core component of the mammalian target of rapamycin complex 2 (mTORC2) with specific siRNA. Together, these findings show that leucine can facilitate the insulin-induced insulin signaling and glucose uptake in skeletal muscle cells through both mTORC1 and mTORC2, implicating the potential importance of this amino acid in glucose homeostasis and providing new mechanistic insights.
    Amino Acids 05/2014; · 3.91 Impact Factor
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    ABSTRACT: Quinocetone (3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide, QCT) is a widely used veterinary drug in P.R. China that promotes feed efficiency and growth of various animals. However, its potential toxicity has been concerned recently. In the present study, we investigated QCT-induced hepatocyte changes and its related mechanism, especially the expression of Nrf2/HO-1 pathway. Oxidative stress induced by QCT in hepatocyte led to DNA damage, inflammation and apoptosis. Nevertheless, hepatocyte has a self-repair system to protect itself from oxidative stress. In the 50 mg/kg/day QCT group, the morphology and function of liver were approximately maintained on normal level, which indicated that the damaged cell might have a self-repair mechanism. Notably, nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway plays a critical role in protecting cells against reactive oxygen species (ROS) generation. However, higher doses of QCT (800 mg/kg/day and 2400 mg/kg/day) inhibited the expression of Nrf2/HO-1 pathway, which resulted in excessive ROS generation and irreversible oxidative DNA damage, inflammation and apoptosis. In conclusion, although QCT-induced oxidative stress activates the expression of Nrf2/HO-1 pathway initially, persistent QCT exposure will inhibit this expression and aggravate hepatocyte damage. Simultaneously, inflammation and apoptosis continues to progress, liver dysfunction and tissue damage will be occurred eventually.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2014; · 2.99 Impact Factor
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    ABSTRACT: Emerging evidence has displayed that oxygen free radicals especially ones promoted by "free" iron play an important role in the development of alcoholic liver disease (ALD). Naturally-occurring quercetin has been reported to prevent ALD and iron overload-induced damage aside from the "free" iron. The purpose was to explore the potential mechanisms by which quercetin arrests alcohol-induced "free" iron disorder. Chronic alcohol (30% of total calories) or iron (0.2%)-fed adult male C57BL/J mice for 15 weeks resulted in significantly elevated levels of hepatic iron, labile iron pool-Fe and serum non-transferrin bound iron, accompanied with sustained oxidative damage. The hepatotoxicity was further exacerbated by ethanol and iron. Quercetin (100 mg/kg. body weight) alleviated the detrimental effects induced by ethanol and/or iron. The expressions of divalent metal transporter 1, zinc transporter member 14, mucolipin 1, transferrin receptor 1 (TfR1) and ferritin were up-regulated by ethanol and/or iron, which were partially normalized by quercetin. Quercetin prevented ethanol-induced hepatotoxicity, which may be partially attributed to the alleviated disorder of bound iron and "free" iron. The significant suppression of ethanol-stimulated molecules for "free" iron uptake and release may contribute to the hepatoprotective effect of quercetin, although TfR1-mediated physiological pathway of iron uptake also played a role.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2014; · 2.99 Impact Factor
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    ABSTRACT: Objective 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. Methods and Results 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 hours. Mice exposed to either ethanol or iron presented significant fatty infiltration and iron deposition in the liver; these symptoms were exacerbated in mice co-treated 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 mRNA 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. Conclusions 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.
    The Journal of nutritional biochemistry 01/2014; · 4.29 Impact Factor
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    ABSTRACT: Quinocetone (3-methyl-2-quinoxalin benzenevinylketo-1,4-dioxide, QCT) is a widely used veterinary drug in PR China that promotes feed efficiency and growth of various animals. However, its potential toxicity has been concerned recently. In the present study, we investigated QCT-induced hepatocyte changes and its related mechanism, especially the expression of Nrf2/HO-1 pathway. Oxidative stress induced by QCT in hepatocyte led to DNA damage, inflammation and apoptosis. Nevertheless, hepatocyte has a self-repair system to protect itself from oxidative stress. In the 50 mg/kg/day QCT group, the morphology and function of liver were approximately maintained on normal level, which indicated that the damaged cell might have a self-repair mechanism. Notably, nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway plays a critical role in protecting cells against reactive oxygen species (ROS) generation. However, higher doses of QCT (800 mg/kg/day and 2400 mg/kg/day) inhibited the expression of Nrf2/HO-1 pathway, which resulted in excessive ROS generation and irreversible oxidative DNA damage, inflammation and apoptosis. In conclusion, although QCT-induced oxidative stress activates the expression of Nrf2/HO-1 pathway initially, persistent QCT exposure will inhibit this expression and aggravate hepatocyte damage. Simultaneously, inflammation and apoptosis continues to progress, liver dysfunction and tissue damage will be occurred eventually.
    Food and Chemical Toxicology. 01/2014; 69:210–219.
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    ABSTRACT: Oxidative stress plays a pivotal role in the intense exercise-induced myocardium injury, and mitochondrial compartment is presumed as the main source and susceptible target of intracellular reactive oxygen species (ROS). The objective of this study was to evaluate the protective effect of quercetin, a naturally occurring flavonoids possessing antioxidant effect on repeated intense exercise-induced mitochondrial oxidative stress and dysfunction. Adult male BALB/C mice were treated by quercetin (100 mg/kg bw) for 4 weeks and subjected to the exercise protocol on a treadmill (28 m/min at 5° slope for 90 min) for seven consecutive days concurrently at the fourth week. Intense exercise in mice resulted in the leakage of creatine kinase-MB (increased from 221.5 ± 33.8 to 151.1 ± 19.1 U/l, P < 0.01) and ultrastructural malformation mainly evidenced by disrupted myofibrils and swollen mitochondria, which was overtly attenuated by quercetin prophylaxis. Quercetin pretreatment evidently alleviated mitochondrial oxidative stress by inhibiting glutathione depletion and aconitase inactivation, ROS over-generation, and lipid peroxidation in cardiac mitochondria of intense exercise mice. Furthermore, mitochondrial dysfunction manifested by decreased mitochondrial membrane potential (68.6 ± 7.6 versus 100.0 ± 7.7 %, P < 0.01) and respiratory control ratio (5.03 ± 0.55 versus 7.48 ± 0.71, P < 0.01) induced as a consequence of acute exercise was markedly mitigated by quercetin precondition. Quercetin protects mouse myocardium against intense exercise injury, especially ultrastructural damage and mitochondrial dysfunction, probably through its beneficial antioxidative effect, highlighting a promising strategy for over-training injury by naturally occurring phytochemicals.
    Arbeitsphysiologie 12/2013; · 2.66 Impact Factor
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    ABSTRACT: Deoxynivalenol (DON) is one of the most common mycotoxins. The aim of this study consists in using diverse cellular and molecular assays to evaluate cytotoxicity, genotoxicity as well as oxidative damage and to investigate their mechanisms in human peripheral blood lymphocytes. The human lymphocytes were cultured in eight different doses of DON (0, 6.25, 12.5, 25, 50, 100, 250 and 500 ng/mL) during 6; 12; and 24 h. DON was able to decrease cell viability and cause damage to the membrane, the chromosomes or the DNA at all times of culture. It was also able to induce lipid peroxidation and raise the levels of 8-OHdG and ROS in 6, 12 and 24 h. The results of the RT-PCR and the Western Blot indicated that DON is able to enhance mRNA or protein expressions of DNA repair genes and HO-1 in 6 h and to inhibit these expressions in 24 h. DON potentially triggers genotoxicity in human lymphocytes. This mechanism is probably related to depletion of antioxidase and oxidative damage to the DNA that reduced expression of HO-1, thereby inhibiting the ability of DNA repair.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 12/2013; · 2.99 Impact Factor
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    ABSTRACT: Though both SLC30A8 rs13266634 SNP and plasma zinc concentrations have been associated with impaired glucose regulation (IGR) and type 2 diabetes (T2D), their interactions for IGR and T2D remain unclear. Therefore, to assess zinc-SLC30A8 interactions, we performed a case-control study in 1,796 participants: 218 newly diagnosed IGR patients, 785 newly diagnosed T2D patients, and 793 individuals with normal glucose tolerance (NGT). After adjustment for age, sex, BMI, family history of diabetes and hypertension, the multivariable OR of T2D associated with a 10-µg/dl higher plasma zinc level was 0.87 (0.85-0.90). Meanwhile, the OR of SLC30A8 rs13266634 homozygous genotypes CC compared with TT was 1.53 (1.11-2.09) for T2D. Similar associations were found in IGR and IGR&T2D groups. Each 10-µg/dl increment of plasma zinc was associated with 22% (OR, 0.78; 95% CI, 0.72-0.85) lower odds of T2D in TT genotype carriers, 17% (0.83; 0.80-0.87) lower odds in CT genotype carriers, and 7% (0.93; 0.90-0.97) lower odds in CC genotype carriers (P for interaction = 0.01). Our study suggested that the C allele of rs13266634 was associated with higher odds of T2D, and higher plasma zinc was associated with lower odds. The inverse association of plasma zinc concentrations with T2D was modified by SLC30A8 rs13266634. Further studies are warranted to confirm our findings and clarify the mechanisms underlying the interaction between plasma zinc and the SLC30A8 gene in relation to T2D.
    Diabetes 12/2013; · 7.90 Impact Factor
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    ABSTRACT: 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 126.6nm, a zeta potential of 40.5mV 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.
    Colloids and surfaces B: Biointerfaces 11/2013; 115C:125-131. · 4.28 Impact Factor
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    ABSTRACT: To investigate the possible molecular mechanisms of heme oxygenase-1 (HO-1) induction by quercetin using rat primary hepatocytes. Sprague-Dawley rat primary hepatocytes were isolated using a two-step collagenase perfusion technique and treated with quercetin at various doses (25 - 200 mumol/L) and times (2 - 12 h). To investigate the roles of various signaling pathways, the hepatocytes were pre-treated with 50 mumol/L quercetin plus an extracellular signal-regulated kinase (ERK) inhibitor (PD98059 at 10 mumol/L), a p38 inhibitor (SB203580 at 10 mumol/L), a c-Jun N-terminal kinase inhibitor (SP600125 at 10 mumol/L) or a phosphatidylinositol 3-kinase inhibitor (Wortmannin at 1 mumol/L) for 12 h. Changes in the mRNA and protein levels of HO-1 and nuclear factor, ethryroid-2 related factor 2 (Nrf2) were detected by RT-PCR and western blotting. After 4 - 12 h of treatment with quercetin at all concentrations, the HO-1 mRNA level in hepatocytes had increased significantly (vs. untreated control cells; all P less than 0.01). The quercetin-induced HO-1 expression and Nrf2 translocation into the nucleolus was inhibited by PD98059. Quercetin may induce HO-1 expression via the ERK/Nrf2 signaling transduction pathway.
    Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 11/2013; 21(11):865-868.
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    ABSTRACT: Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, is still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8mg/kg for mice or 20μmol/L for heaptocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals.
    Toxicology and Applied Pharmacology 08/2013; · 3.98 Impact Factor
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    ABSTRACT: Our aim was to study whether there is causal association between serum uric acid and metabolic syndrome (MetS). A cross-sectional study was performed, including a total of 27,009 subjects (23,345 subjects having uric acid data) from the Dongfeng-Tongji Cohort study. The MetS was defined by the International Diabetes Foundation criteria of 2005. Association analysis was performed by logistic regression. A genetic risk score was calculated by adding the uric acid increasing alleles in two SNPs (rs11722228 in SLC2A9 and rs2231142 in ABCG2) which were identified from our genome-wide association study on uric acid levels. The causal association was examined by mendelian randomization analysis. Among a middle- and old-age Chinese population, serum uric acid concentrations were strongly associated with the risk of MetS and its several components (P < 0.0001). The effects were stronger in women than in men. Despite the lack of statistical significance, both SNPs exhibited a trend with increased MetS risk (rs11722228, OR = 1.06, 95 % CI 0.99-1.14; rs2231142, OR = 1.02, 95 % CI 0.95-1.10), consistent with their increasing uric acid effects. Each additional uric acid increasing allele in the genetic risk score was associated with 3 % increased MetS risk (OR = 1.03, 95 % CI 0.98-1.09; P = 0.23). Further adjustment for serum uric acid attenuated the trend of individual SNP and genetic risk score with increased MetS risk (all OR < 1.0). These findings suggested that serum uric acid was associated with MetS risk in a middle- and old-age Chinese population. Whether this association was causal remained to be investigated in the future studies.
    European Journal of Epidemiology 07/2013; · 5.12 Impact Factor
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    ABSTRACT: 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 4 groups with doses of 2400, 800, 50 and 0 mg/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.
    Regulatory Toxicology and Pharmacology 04/2013; · 2.13 Impact Factor
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    ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in P.R. China. But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated. AIM OF THE STUDY: The present study was aimed at evaluating potential reproductive and developmental toxicities of Pu-erh black tea extract (BTE) in Sprague Dawley rats. MATERIALS AND METHODS: Growing rats were given BTE by gavage at levels of 0, 200, 700 and 2500mg/kg/day as the F0 generation in reproductive toxicity study. Additionally, BTE was administered to mate female rats from gestation day 0.5 through 19.5 at the doses of 0, 200, 700 and 2500mg/kg/day to evaluate the developmental toxicity. RESULTS: In the reproductive toxicity study, only 2500mg/kg/day BTE reduced the body weight gain and altered the relative organ weights including testes, prostata and ovary both for F0 parents and F1 offspring compared to the controls. High dose of BTE (2500mg/kg/day) administration caused developmental disturbances in embryo-to- foetus period including resorbed embryos, decreased embryo size and skeletal anomalies. CONCLUSION: In conclusion, the no-observed-adverse-effect level of BTE is 700mg/kg/day both for reproductive toxicity and developmental toxicities.
    Journal of ethnopharmacology 04/2013; · 2.32 Impact Factor
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    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.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 04/2013; · 2.97 Impact Factor
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    ABSTRACT: SCOPE: This study investigated the effect of chronic leucine supplementation on insulin sensitivity and the associated mechanisms in rats on high-fat diet (HFD). METHODS AND RESULTS: Male Sprague-Dawley rats were fed either normal chow diet or HFD supplemented with 0, 1.5, 3.0, and 4.5% leucine for 24 weeks. We found that chronic leucine supplementation increased insulin sensitivity together with increased body weight in rats on HFD, but had no effect on insulin sensitivity in rats on normal chow diet. The increased insulin sensitivity by leucine supplementation was not associated with altered ectopic fat accumulation in liver and muscle, plasma levels of lipids and cytokines, but is associated with reduced oxidative stress and improved insulin signaling. Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues. CONCLUSION: Chronic leucine supplementation can increase insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in rats on HFD.
    Molecular Nutrition & Food Research 02/2013; · 4.31 Impact Factor
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    ABSTRACT: In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt-or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt473 and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or 2 complexes, but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly.
    Journal of Biological Chemistry 02/2013; · 4.65 Impact Factor
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    ABSTRACT: 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.
    Respiratory medicine 01/2013; · 2.33 Impact Factor

Publication Stats

614 Citations
226.72 Total Impact Points

Institutions

  • 2002–2014
    • Huazhong University of Science and Technology
      • School of Public Health
      Wu-han-shih, Hubei, China
  • 2011–2012
    • Huazhong Agricultural University
      • College of Food Science and Technology
      Wuhan, Hubei, China
  • 2009
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 2007
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany