RESUMO
Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0-4.0 nm. They exhibited well-separated dual emission in the visible region (500-590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from - 23.9 to - 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.
Assuntos
Nanopartículas , Pontos Quânticos , Humanos , Diagnóstico por Imagem , Células HeLa , ÁguaRESUMO
BACKGROUND/AIMS: Regional hypoxia promptly develops after trauma because of microvascular injury and increased oxygen consumption. This acute hypoxia plays a positive role in early skin wound healing. One of the mechanisms underlying the beneficial effects of acute hypoxia on wound healing may be increased hypoxia-inducible factor-1 (HIF-1α) expression. HIF-1α may affect the wound-healing process through many aspects, including angiogenesis, metabolism, and extra-cellular matrix synthesis and remodelling. Epidermal stem cells (EpSCs) are important participants in wound repair; however, whether these cells are regulated by hypoxia is unclear. This study aimed to elucidate the regulatory mechanism by which hypoxia acts on EpSCs. METHODS: CCK8 assays, western blots and live cell station observation were employed to compare the viability, proliferation and motility of EpSCs cultured under normoxic conditions (21% O2) with those cultured under hypoxic conditions (2% O2). Moreover, we used FG-4592 (a prolyl hydroxylase inhibitor that stabilizes HIF-1α in normoxia), KC7F2 (a selective inhibitor of HIF-1α transcription) and siRNA against HIF-1α to regulate HIF-1α expression. RESULTS: Acute hypoxia caused EpSCs to switch from a quiescent state to an activated state with higher viability and motility, as well as an earlier proliferation peak. We demonstrated that the HIF-1 signalling pathway mediated hypoxia-induced activation of EpSCs. Finally, the in vivo experiments showed that exogenous FG-4592 effectively accelerates wound healing, shortens healing times and even induces epidermal hyperplasia. CONCLUSION: This study demonstrated that both hypoxia and exogenous FG-4592 improve EpSC proliferation and motility by stabilizing HIF-1α, and its results suggest that HIF-1α is an important target through which wound healing can be accelerated and that FG-4592 is a promising new drug for wound repair.
Assuntos
Epiderme/efeitos dos fármacos , Glicina/análogos & derivados , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoquinolinas/uso terapêutico , Estabilidade Proteica/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Epidérmicas , Epiderme/metabolismo , Epiderme/patologia , Glicina/farmacologia , Glicina/uso terapêutico , Isoquinolinas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismoRESUMO
Previously, we showed that 0.5% quercetin simultaneously decreased serum homocysteine and glutathione (GSH) levels in rats. The aim of the present study was to investigate the effects of 0.5% quercetin on GSH metabolism, related enzymes and signal pathways in rats. Rats were fed the control diet and 0.5% quercetin-supplemented diet for 6 weeks. The results showed that quercetin reduced serum and hepatic content of GSH and the ratio of GSH and oxidized glutathione (GSSG), enhanced hepatic activity and mRNA expression of glutathione S-transferase (GST), inhibited hepatic activity and mRNA expression of glutamate cysteine ligase (GCL), and decreased hepatic glutathione reductase (GR) mRNA expression. Levels of phosphorylated p38 and extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinases (MAPKs) increased, while that of nuclear factor E2-like 2 (Nrf2) protein decreased after quercetin treatment. However, no significant hepatotoxicity was noted. We concluded that quercetin treatment altered hepatic GSH metabolism by modulating GSH metabolic enzyme activities and mRNA expression in rats, and p38, ERK1/2 MAPKs, and Nrf2 were involved in modulating GSH metabolism-related enzymes.
RESUMO
Vegetables vary greatly in antioxidant capacity in vitro. This study was to investigate the actions of three vegetables different remarkably in antioxidant capacity in vitro on antioxidant function in aged rats. Sixty female aged Wistar rats were randomly assigned to the control, lotus root, rape and cucumber (high, moderate and low in antioxidant capacity, respectively) treated groups. After 6 weeks of feeding, there were no significant differences in plasma FRAP value and contents of vitamin C, vitamin E, uric acid and total phenolics among different groups, whereas the content of reduced glutathione was significantly higher in the rape and cucumber groups. Plasma superoxide dismutase activity also was significantly increased in the rape and cucumber groups. Plasma contents of malondialdehyde, carbonyls and hemolysis were decreased significantly in 3 vegetable-treated groups. Meanwhile, urinary 8-hydroxy-2'-deoxyguanosine excretion was lower significantly in the rape group and the ratio of comet tail length to total length of blood mononuclear cells was decreased significantly in 3 vegetables treated groups. These results suggest that 3 vegetables tested are effective in improving antioxidant function to some extent in aged rats and no correlation is found between antioxidant capacity in vitro and improvements of antioxidant function. The benefits observed in this study may come from additive or synergistic combinations of antioxidants contained in vegetables.
RESUMO
Aging weakened innate and adaptive immunity both quantitatively and qualitatively. Some components in propolis could stimulate immune function in young animals or cultured immune cells in vitro. Few studies had been carried out in the aged. The present study was to evaluate the effects of Brazilian green propolis supplementation on the immunological parameters in aged mice. Eighty Kunming mice, aged 15-18 months, were randomly assigned to the control and three experimental groups supplemented with different doses (83.3, 157.4 and 352.9 mg/kg.bw respectively) of Brazilian green propolis. The experiment lasted for 4 weeks. Contents of total polyphenol, flavonoid, cinnamic acid and artepillin-C in Brazilian green propolis were analyzed. Splenic NK cytotoxic, T lymphocyte proliferation and antibody generation cells, as well as the phagocytosis of peritoneal macrophages, ear swelling, and serum contents of IgG, IgM, hemolysin and cytokines were measured. After 4 weeks of treatment, the phagocytosis of peritoneal macrophages was enhanced in 157.4 mg/kg and 352.9 mg/kg groups. Ear swelling increased in all propolis treatmented groups. Antibodies specific to sheep erythrocytes were higher in the groups receiving 157.4 and 352.9 mg/kg.bw than that of control group. IgG level dramatically increased in the groups receiving 83.3 and 157.4 mg/kg.bw in comparison to the control group. These results indicate that administration of Brazilian green propolis have a positive effect on innate and adaptive immunity in aged mice.
RESUMO
BACKGROUND: Despite advances in research on psychopathology and social media use, no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019 (COVID-19) outbreak. AIM: To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak. METHODS: We used Bibliometrix (an R software package) to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection, PubMed, and Scopus databases. RESULTS: Such research output was scarce before COVID-19, but exploded after the pandemic with the publication of a number of high-impact articles. Key authors and institutions, located primarily in developed countries, maintained their core positions, largely uninfluenced by COVID-19; however, research production and collaboration in developing countries increased significantly after COVID-19. Through the analysis of keywords, we identified commonly used methods in this field, together with specific populations, psychopathological conditions, and clinical treatments. Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression, with depression detection becoming a new trend. Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions, and more in-depth clinical studies should be conducted in the future. CONCLUSION: After COVID-19, there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.
RESUMO
BACKGROUND: DNA base-excision repair genes hOGG1 and XRCC1 play an important role in preserving genetic stability in mammalian cells against any damage caused by different factors. However, it is unclear whether altered expression and function of these DNA repair genes could lead to hepatocellular carcinoma (HCC) susceptibility. AIMS: This study determined the association between polymorphisms of the genes encoding two key proteins of DNA base excision repair (hOGG1 ser326Cys and XRCC1 Arg 280His) and HCC risk. METHODS: A total of 350 HCC patients (mean age of 51.1 years) and 400 healthy controls (mean age of 51.4 years) were recruited for analysis of XRCC1 and hOGG1 gene polymorphisms using PCR plus restriction fragment length polymorphism (PCR-RFLP). RESULTS: The data showed that the hOGG1 Cys326Cys and Ser326Cys genotypes were associated with increase in HCC risk. In contrast, there was no association between HCC susceptibility and the distribution of XRCC1 His 280 His and Arg280His. However, combination of these two gene polymorphisms (XRCC1-280 Arg and hOGG1-326Cys) is associated with significant induction of HCC risk. In addition, the data also showed that XRCC1 280His polymorphism was associated with HBV infection and HCC family history to increase HCC risk. The hOGG1 326cys genotype was associated with alcohol consumption, tobacco smoke, and HBV infection to increase HCC risk. CONCLUSION: The data from the current study demonstrated the association of these two DNA repair gene polymorphisms with HCC risk. Future studies will confirm these data before they can be used as a biomarker for assessing HCC risk.
Assuntos
Carcinoma Hepatocelular/metabolismo , DNA Glicosilases/metabolismo , Reparo do DNA/genética , Proteínas de Ligação a DNA/metabolismo , Predisposição Genética para Doença , Polimorfismo Genético , Adulto , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , DNA Glicosilases/genética , Proteínas de Ligação a DNA/genética , Feminino , Regulação da Expressão Gênica , Marcadores Genéticos , Genótipo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
It is imperative to search the eco-friendly and cost-effective technologies for degrading contaminants. Coupling the effect of Ti/PbO2 at the anode with heterogeneous electro-Fenton was an efficient method. Industrial pyrite waste slag characterized by a variety of methods had catalytic performance and stable performance to activate hydrogen peroxide (H2O2) into hydroxyl radical (âOH). Meanwhile, the processing conditions, the malachite green wastewater concentration, the current density, the pH range, and the dosage of industrial pyrite waste slag were emphatically optimized. Herein, the total organic carbon (TOC) removal efficiency reached 97.70%, the mineralization current efficiency (MCE) was 0.392%, and the energy consumption (EC) was 1.942 kWh/m3 after 240 min. Heterogeneous Ti/PbO2-electro-Fenton using industrial pyrite waste slag as catalyst was an environmentally friendly technology and provided a recycling method with traditional wastes. Finally, catalytic mechanisms and possible pathways were represented according to the results of quantum chemistry calculations and gas chromatography-mass spectrometry (GCMS).
Assuntos
Resíduos Industriais , Poluentes Químicos da Água , Corantes , Eletrodos , Peróxido de Hidrogênio/química , Resíduos Industriais/análise , Ferro , Metano , Oxirredução , Sulfetos , Titânio/análise , Águas Residuárias/química , Poluentes Químicos da Água/análiseRESUMO
Coal tar wastewater is hard to degrade by traditional methods because of its toxic pollutant constituents and high concentration of aromatic hydrocarbons, especially phenolic substances. A new type of hydrophobic benzacetone modified PbO2 anode (BA-PbO2 electrodes) was used for the electrocatalytic treatment of coal tar wastewater in a continuous cycle reactor. The surface morphology, structure, valences of elements, hydrophobicity, hydroxyl radical (·OH) produced capacity, electrochemical properties and stability of BA-PbO2 electrodes were characterized by SEM (scanning electron microscopy), XRD (X-ray diffraction), XPS (X-ray photoelectron spectroscopy), contact angle, a fluorescence probe test, an electrochemical workstation and accelerated life test, respectively. The BA-PbO2 electrodes exhibited a compact structure and finely dispersed crystallize size of 4.6 nm. The optimum degradation conditions of coal tar wastewater were as follows: current density of 90 mA cm-2, electrode gap of 1 cm and temperature at 25 °C with flow velocity of 80 L h-1. The chemical oxygen demand (COD) removal efficiency reached 92.39% after 240 min of degradation under the optimized conditions and the after-treatment COD value was 379.51 mg L-1 which was lower than the centralized emission standard (less than 400 mg L-1). These findings demonstrated the feasibility and efficiency of electrocatalytically degrading coal tar wastewater by BA-PbO2 electrodes. The possible mechanism and pathway for phenol a specific pollutant in coal tar wastewater were investigated by quantum chemistry calculations (Multiwfn) and gas chromatography-mass spectrometry (GC-MS). The toxicity of each intermediate was predicted by the ECOSAR program.
Assuntos
Alcatrão , Poluentes Químicos da Água , Butanonas , Eletrodos , Interações Hidrofóbicas e Hidrofílicas , Chumbo , Oxirredução , Óxidos , Titânio , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
Fluorescent non-conjugated nanoparticles without any π-aromatic building blocks are of great interest in biological applications due to their low cytotoxicity and biocompatibility. Herein, the non-conjugated AIE-active polymer nanoparticles bearing ß-cyclodextrin (ß-CD-PNs) were obtained through self-assembly of amphiphilic poly(isobutylene-alt-maleic anhydride)-g-ß-CD (PIMA-g-ß-CD). Unexpectedly, ß-CD-PNs without conventional AIE fluorophores showed strong fluorescence emission in the aggregated state, excellent photostability and water-solubility. More interestingly, ß-CD-PNs showed excellent biocompatibility and low biotoxicity after being co-incubated with HeLa cells and passaged several times. As a result, the strong blue fluorescence signals could still be detected in HeLa cells after up to 15 generations of passages and showed complete cell morphology. Furthermore, ß-CD-PNs could also be used in zebrafish for bioimaging. The results indicated that ß-CD-PNs was a good choice as a tracer for long-term cell tracking and in vivo imaging agent. Our research provided an effective strategy for developing low-toxicity bioprobes based on ß-CD.
Assuntos
Nanopartículas , Polímeros , Animais , Rastreamento de Células , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Iodeto de Potássio , Peixe-ZebraRESUMO
OBJECTIVE: To explore metabolic changes after acute hypoxia and modulating effect of vitamins B1, B2, and PP supplementation in mice exposed to acute hypoxia. METHODS: Fifty male Kunming mice were randomly divided into 5 groups: normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time-vitamins B1, B2, and PP supplementation. All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6,000 meters for 8 h, except for the normal group. Nuclear magnetic resonance analysis was used to identify the changes of serum metabolic profiles. RESULTS: There were significant changes in some serum metabolites under induced acute hypoxia, essentially relative increase in the concentrations of lactate, sugar and lipids and decrease in ethanol. The serum levels of choline, succinate, taurine, alanine, and glutamine also increased and phosphocholine decreased in the acute hypoxia group. After vitamins B1, B2, and PP supplementation, all these metabolic changes gradually recovered. CONCLUSIONS: Significant changes in serum metabolic profile were observed by metabolomics in mice exposed to acute hypoxia, and vitamins B1, B2, and PP supplementation proved to be beneficial to improving some metabolic pathways. It is suggested that the dietary intakes of vitamins B1, B2, and PP should be increased under hypoxia condition.
Assuntos
Hipóxia/sangue , Hipóxia/metabolismo , Metabolômica/métodos , Fenômenos Fisiológicos da Nutrição/efeitos dos fármacos , Complexo Vitamínico B/uso terapêutico , Doença Aguda , Animais , Relação Dose-Resposta a Droga , Metabolismo dos Lipídeos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Análise de Componente Principal , Riboflavina/administração & dosagem , Riboflavina/uso terapêutico , Tiamina/administração & dosagem , Tiamina/uso terapêutico , Complexo Vitamínico B/administração & dosagemRESUMO
OBJECTIVE: To analyse the plasma contents of querceitn and its metabolites in portal vein in rats. METHODS: Male Wistar rats were orally administrated with quercetin at the dose of 40 mg/kg. The blood samples were corrected from the portal vein 1 h later. The quercetin and its metabolites in plasma were analysed with high performance liquid chromatography-mass spetrometry (HPLC-MS) method. RESULTS: The quercetin, quercetin-3-glucuronide, quercetin glucuronide sulfate, 3'-O-methylated quercetin, 4'-O- methylated quercetin and quercetin sulfate were detected in portal vein. CONCLUSION: The results indicated that the quercetin was extensively metabolized in intestine and entered the portal vein in various forms after administration.
Assuntos
Antioxidantes/farmacocinética , Veia Porta , Quercetina/sangue , Quercetina/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Espectrometria de Massas/métodos , Veia Porta/metabolismo , Quercetina/administração & dosagem , Quercetina/análogos & derivados , Quercetina/metabolismo , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
INTRODUCTION: Propolis is a natural product with many biological activities. The present study was designed to evaluate the effects of Chinese propolis on glucose metabolism, antioxidant function, and inflammatory cytokines in patients with type 2 diabetes mellitus (T2DM). METHODS: In the 18-week study, recruited T2DM patients were randomly divided into a Chinese propolis group (900 mg/day) (n = 31) and a control group (n = 30) according to fasting serum glucose levels at baseline. RESULTS: At the end of the study, no significant difference was found between the groups in serum glucose, glycosylated hemoglobin, insulin, aldose reductase, or adiponectin. However, serum GSH, flavonoids, and polyphenols were significantly increased, and serum lactate dehydrogenase activity was significantly reduced in the Chinese propolis group. Meanwhile, serum IL-6 was significantly increased in the Chinese propolis group. CONCLUSION: Chinese propolis is effective at improving antioxidant function in T2DM patients, partly by increasing serum antioxidant parameters.
RESUMO
This study was aimed to observe the effects of vitamin B1, vitamin B2, and niacin supplementation on hepatic gene expression profiles in mice exposed to acute hypoxia. Thirty mice were randomly divided into normal, acute hypoxia, and acute hypoxia plus vitamin B1, vitamin B2, and niacin supplementation groups and fed corresponding diets for 2 weeks and then exposed to a simulated altitude of 6000 m for 8 h. Hepatic gene expression profiles were analyzed using a microarray technique. Several biochemical markers were also assayed. The results showed that a total of 2476 genes were expressed differentially after acute hypoxia exposure (1508 upregulated genes and 968 downregulated genes). Compared with the acute hypoxia group, there were 1382 genes differentially expressed (626 upregulated genes and 756 downregulated genes) in the acute hypoxia plus vitamin B1, vitamin B2, and niacin supplementation group. Pathway analysis indicated that carbohydrate, lipid, and amino acid metabolism, as well as electron transfer chain, were improved to some extent after vitamin B1, vitamin B2, and niacin supplementation. Supportive results were obtained from biochemical assays. Our findings suggest that the supplementation of vitamin B1, vitamin B2, and niacin is beneficial in improving nutritional metabolism partly via gene expression under acute hypoxia condition.
Assuntos
Suplementos Nutricionais , Metabolismo Energético/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Hipóxia/tratamento farmacológico , Fígado/efeitos dos fármacos , Niacina/farmacologia , Riboflavina/farmacologia , Tiamina/farmacologia , Doença Aguda , Animais , Modelos Animais de Doenças , Metabolismo Energético/genética , Regulação da Expressão Gênica , Hipóxia/genética , Hipóxia/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Tempo , TranscriptomaRESUMO
OBJECTIVE: To investigate the effect of various cooking methods on the contents of major flavonoids in vegetables, and to provide basic data for researches on the relationship between flavonoid and health. METHODS: Nine kinds of vegetables obtained from Tianjin market were cooked by frying, boiling, stewing, microwave cooking respectively, then the contents of flavonoids in vegetables and soups after cooking were determined by HPLC. RESULTS: The reserving rates of flavonoids after frying, boiling, stewing and microwave cooking ranged from 54.6% to 115.6%, 33.6% to 107.8%, 31.7% to 100.5%, and 43.1% to 109.6% respectively. Parts of flavonoids were also transfered to the soup after cooking. The transferring rate ranged from 1.4% to 55.8%. CONCLUSION: Cooking often affected the flavonoids in vegetables in some degree, and various cooking methods exerted different effects on the content of flavonoids.
Assuntos
Culinária/métodos , Flavonoides/análise , Verduras/química , Cromatografia Líquida de Alta PressãoRESUMO
Riboflavin deficiency is widespread in many regions over the world, especially in underdeveloped countries. In this study, we investigated the effects of riboflavin deficiency on protein expression profiles in HepG2 cells in order to provide molecular information for the abnormalities induced by riboflavin deficiency. HepG2 cells were cultured in media containing different concentrations of riboflavin. Changes of cell viability and apoptosis were assessed. A comparative proteomic analysis was performed using a label-free shotgun method with LC-MS/MS to investigate the global changes of proteomic profiles in response to riboflavin deficiency. Immunoblotting test was used to validate the results of proteomic approach. The cell viability and apoptosis tests showed that riboflavin was vital in maintaining the cytoactivity of HepG2 cells. The label-free proteomic analysis revealed that a total of 37 proteins showing differential expression (±2 fold, p < 0.05) were identified after riboflavin deficiency. Bioinformatics analysis indicated that the riboflavin deficiency caused an up-regulation of Parkinson's disease pathway, steroid catabolism, endoplasmic reticulum stress and apoptotic process, while the fatty acid metabolism, tricarboxylic citrate cycle, oxidative phosphorylation and iron metabolism were down-regulated. These findings provide a molecular basis for the elucidation of the effects caused by riboflavin deficiency.
Assuntos
Doença de Parkinson/genética , Deficiência de Riboflavina/genética , Riboflavina/genética , Animais , Apoptose/genética , Sobrevivência Celular/genética , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/genética , Doença de Parkinson/patologia , Proteoma/genética , Deficiência de Riboflavina/patologia , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: To investigate the effects of mitogen-activated protein kinases (MAPKs) inhibitors on glutathione (GSH) metabolism, and to explore the pathway related to GSH metabolism. METHODS: BRL rat hepatocytes were treated by c-Jun NH2-terminal kinase (JNK),p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors:SP600125, SB203580 and PD98659, respectively, for 24 h. MTT method was used to measure hepatocytes viability. The content of GSH was determined by high performance liquid chromatography. The protein expressions of JNK and phosphorylated JNK (p-JNK) was tested by Luminex method. Activities of GSH metabolic enzymes were detected by commercial kits. RESULTS: Hepatocytes vitality was inhibited when the concentrations of SP600125, SB203580 and PD98659 were higher than 10 µmol/L, 20 µmol/L, and 40 µmol/L, respectively; SP600125 decreased the content of GSH in hepatocytes, while SB203580 and PD98659 had no effect. SP600125 reduced p-JNK protein expression, and enhanced GSH-Px activity significantly. CONCLUSIONS: JNK MAPK pathway takes part in the GSH metabolism in hepatocytes.
Assuntos
Inibidores Enzimáticos/farmacologia , Glutationa/metabolismo , Hepatócitos/enzimologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Animais , Células Cultivadas , Hepatócitos/efeitos dos fármacos , RatosRESUMO
Urinary riboflavin excretion and erythrocyte glutathione reductase activation coefficient are frequently applied in determining riboflavin requirement. Previously, we found that plasma riboflavin is a sensitive marker in the assessment of riboflavin status in rat models. Here, we hypothesize that plasma riboflavin is a useful maker in studying riboflavin requirement. This study examines the changes of fasting plasma riboflavin and urinary riboflavin excretion in response to different riboflavin intake levels in Chinese male adults. The estimated average requirement (EAR) of riboflavin was extrapolated. Seventy-eight participants were randomly divided into the control and 5 riboflavin-supplemented groups. A 6-week riboflavin supplementation was performed at the doses of 0, 0.2, 0.4, 0.6, 0.8, or 1.0 mg daily. The energy expenditure was 15.4 ± 1.9 MJ/d, as estimated by the 24-hour physical activity recording method. Dietary riboflavin intake was 1.0 ± 0.2 mg/d, based on chemical analysis. The fasting plasma riboflavin was increased significantly in a dose-dependent manner when the supplemented riboflavin exceeded 0.4 mg/d and the EAR of riboflavin was suggested to be between 1.3 and 1.5 mg/d. In addition, we found a significant increase in fasting urinary riboflavin excretion when the supplemented riboflavin exceeded 0.6 mg/d. The critical point was calculated as 1.4 mg/d, based on the intersecting point of the 2 regression lines at lower and higher riboflavin intakes. These findings demonstrate that plasma riboflavin is a sensitive marker for riboflavin status, and the EAR of riboflavin for Chinese male adults is 1.4 mg.
Assuntos
Povo Asiático , Necessidades Nutricionais , Riboflavina/sangue , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal , Dieta , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Metabolismo Energético , Eritrócitos , Exercício Físico , Jejum , Humanos , Masculino , Avaliação Nutricional , Riboflavina/administração & dosagem , Riboflavina/urina , Adulto JovemRESUMO
Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and cholesterol efflux.