RESUMO
BACKGROUND: Potential protection against the neurotoxic damages of high levels of fluoride on rats and SH-SY5Y cells by extract of Ginkgo biloba leaves, as well as underlying mechanisms, were examined. METHODS: The rats were divided randomly into 4 groups, i.e., control, treatment with the extract (100 mg/kg body weight, gavage once daily), treatment with fluoride (50 ppm F- in drinking water) and combined treatment with both; SH-SY5Y cells exposed to fluoride and fluoride in combination with the extract or 4-Amino-1,8-naphthalimide (4-ANI), an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1). Spatial learning and memory in the rats were assessed employing Morris water maze test; the contents of fluoride in brains and urine by fluoride ion-selective electrode; cytotoxicity of fluoride was by CCK-8 kit; the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the content of malondialdehyde (MDA) by appropriate kits; the level of 8-hydroxydeoxyguanosine (8-OHdG) was by ELISA; the content of ROS and frequency of apoptosis by flow cytometry; the expressions of phospho-histone H2A.X(Ser139), PARP-1, poly (ADP-ribose) (PAR) and Sirtuin-1 (SIRT1) by Western blotting or immunofluorescence. RESULTS: The rats with prolong treatment of fluoride exhibited dental fluorosis, the increased contents of fluoride in brains and urine and the declined ability of learning and memory. In the hippocampus of the rats and SH-SY5Y cells exposed to fluoride, the levels of ROS, MDA, apoptosis, 8-OHdG and the protein expressions of histone H2A.X(Ser139), PARP-1 and PAR were all elevated; the activities of SOD and GSH-Px and the protein expression of SIRT1 reduced. Interestingly, the treatment of Ginkgo biloba extract attenuated these neurotoxic effects on rats and SH-SY5Y cells exposed to fluoride and the treatment of 4-ANI produced a neuroprotective effect against fluoride exposure. CONCLUSION: Ginkgo biloba extract attenuated neurotoxic damages induced by fluoride exposure to rats and SH-SY5Y cells and the underlying mechanism might involve the inhibition of PARP-1 and the promotion of SIRT1.
Assuntos
Fluoretos , Neuroblastoma , Humanos , Animais , Ratos , Fluoretos/farmacologia , HistonasRESUMO
BACKGROUND: High birth weight (HBW) is associated with childhood obesity, but with inconsistent results. This study investigated the relationship between HBW and childhood obesity, and further explored the interaction of HBW with behavioral and socio-economic determinants of obesity. METHODS: This cross-sectional study enrolled 1906 grade-two children of Guangzhou, China, from June to November, 2016. Overweight/obesity corresponded to a body mass index higher than the sex-age-specific criteria. Abdominal obesity was assessed using the sex-specific waist-height ratio cutoffs. The association of HBW with obesity was evaluated in multivariable logistic regression model. The relative excess risk due to interaction (RERI) and the attributable proportion of interaction (AP) indices were used to measure additive interaction, while applying the interaction of OR index for multiplicative interaction assessment. RESULTS: Children with HBW had an increased risk of overweight/obesity [odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.56-3.76] compared with those without HBW. Significant additive interaction of HBW with physical activity was found for overweight/obesity [relative excess risk due to interaction (RERI) = 2.69, 95% CI = 0.62-4.75; attributable proportion of interaction (AP) = 0.72, 95% CI = 0.42-1.02]. The HBW children with insufficient activity had higher odds of overweight/obesity compared to the non-HBW children with sufficient activity (OR = 3.75, 95% CI = 2.06-6.83). In addition, we identified a significant interaction of HBW with household income for abdominal obesity (RERI = 1.20, 95% CI = 0.02-2.37; AP = 0.76, 95% CI = 0.16-1.36). CONCLUSIONS: HBW confers an increased risk for childhood overweight/obesity. Physical activity attenuates the effect of HBW on overweight/obesity, and HBW possibly synergistically interacts with high household income to promote abdominal obesity in childhood.
Assuntos
Peso ao Nascer , Exercício Físico , Obesidade Infantil/epidemiologia , Criança , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Masculino , Fatores de Risco , Fatores SocioeconômicosRESUMO
DcCDPK8 involved in abiotic stress such as low temperature and signal transduction of hormones ABA and MeJA,but the transcriptional regulation is still unclear. In order to study the core promoter region of DcCDPK8 gene in Dendrobium catenatum and explore its transcriptional regulation mechanism,the DcCDPK8 gene promoter sequence was cloned by PCR from D. catenatum. Promoter sequence function was studied by fusion of 5 'terminal deletion and GUS gene. The results showed that the promoter sequence of DcCDPK8 gene has a low-temperature responsive element( LTR) between~(-1) 749 bp and-614 bp,two MeJA responsive elements between~(-1) 749 bp and-230 bp,and one ABA responsive elements between-614 bp and-230 bp. Three 5'-end different deletion fragments were constructed to fuse the eukaryotic expression vectors p BI121 with GUS,which were transformed into tobacco leaves. The GUS activity under cold stress treatment was DcCDPK8-p1>DcCDPK8-p2>DcCDPK8-p3. GUS activity under exogenous ABA induction was DcCDPK8-p1>DcCDPK8-p2>DcCDPK8-p3,and GUS activity under exogenous MeJA induction was DcCDPK8-p1>DcCDPK8-p2>DcCDPK8-p3. It is speculated that the ABA response element( ARE) in the promoter sequences of DcCDPK8 is positive regulatory role in response to exogenous ABA,the MeJA cis-acting element plays a negative role in response to exogenous MeJA.
Assuntos
Dendrobium/genética , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , Elementos de Resposta , Estresse Fisiológico , Ácido Abscísico , Acetatos , Clonagem Molecular , Temperatura Baixa , Ciclopentanos , Regulação da Expressão Gênica de Plantas , Oxilipinas , Plantas Geneticamente Modificadas , NicotianaRESUMO
Common burden tests have different statistical performance in genetic association studies of rare variants. Here, we compare the statistical performance of burden tests, such as CMC, WST, SUM and extension methods, using the computer-simulated datasets of rare variants with different parameters of sample sizes, linkage disequilibrium (LD), and different numbers of mixed non-associated variants. The simulation results showed that the type I error for all methods is near 0.05. When the rare variants had the same direction of effect, the higher LD and the less non-associated variants, the higher the power of these method, except the data adaptive SUM test. When the direction was different, the power was significantly reduced for all methods. The methods that consider the direction yielded larger statistical power than those methods without considering the effect direction, except the strong LD condition. And the larger the sample size, the larger the power. The statistical performance of burden tests is affected by a variety of factors, including the sample size, effect direction of variants, non-associated variants, and LD. Therefore, when choosing the method and setting the collection unit and weight, the prior biological information of genetic variation should be integrated to improve study efficiency.
Assuntos
Algoritmos , Bioestatística/métodos , Estudos de Associação Genética/métodos , Variação Genética , Simulação por Computador , Predisposição Genética para Doença/genética , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Modelos GenéticosRESUMO
OBJECTIVE: To evaluate the usefulness of the thyroglobulin (Tg) level in adults as a nutritional biomarker of iodine status and to identify the factors related to the serum Tg level. METHODS: A cross-sectional study was conducted in adult populations of areas differing in iodine nutrition from three provinces (Autonomous Region) in China. Serum levels of thyroid hormones and Tg as well as thyroid autoantibodies were measured. The thyroid volume and nodule were measured by ultrasound. A multivariate linear regression analysis was used to assess iodine intake and other indeterminate factors associated with the serum Tg level. RESULTS: A total of 573 adults were recruited for this study. The serum Tg levels differed significantly among the three groups (22.27 µg/L, 9.73 µg/L and 15.77 µg/L in the excess, more-than-adequate, and deficient groups, respectively). The results of multivariate linear regression analysis indicate that excess and deficient iodine intake, goiter, thyroid nodule, hypothyroidism are significantly related with higher Tg level, and TgAb positivity is significantly related with lower serum Tg. CONCLUSION: The serum Tg level reflects abnormal thyroid function and is a sensitive functional biomarker of iodine nutrition status.
Assuntos
Iodo , Tireoglobulina/sangue , Doenças da Glândula Tireoide/sangue , Glândula Tireoide/metabolismo , Adulto , Biomarcadores/sangue , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Epidemiological investigations indicate that certain ingredients in tea bricks can antagonize the adverse effects of fluoride. Tea polyphenols (TPs), the most bioactive ingredient in tea bricks, have been demonstrated to be potent bone-supporting agents. ClC7 is known to be crucial for osteoclast (OC) bone resorption. Thus, in this study, we investigated the potential protective effects of TPs against fluorosis using a mouse model and explored the underlying mechanisms with particular focus on ClC7. A total of 40, healthy, 3weekold male C57BL/6 mice were randomly divided into 4 groups (n=10/group) by weight as follows: distilled water (control group), 100 mg/l fluoridated water (F group), water containing 10 g/l TPs (TP group) and water containing 100 mg/l fluoride and 10 g/l TPs (F + TP group). After 15 weeks, and after the mice were sacrificed, the long bones were removed and bone marrow-derived macrophages were cultured ex vivo in order to perform several experiments. OCs were identified and counted by tartrateresistant acid phosphatase (TRAP) staining. The consumption of fluoride resulted in severe fluorosis and in an impaired OC function [impaired bone resorption, and a low mRNA expression of nuclear factor of activated T-cells 1 (NFATc1), ATPase H+ transporting V0 subunit D2 (ATP6v0d2) and osteopetrosisassociated transmembrane protein 1 (Ostm1)]. In the F + TP group, fluorosis was attenuated and OC function was restored, but not the high bone fluoride content. Compared with the F group, mature OCs in the F + TP group expressed higher mRNA levels of ClC7 and Ostm1; the transportation and retaining of Cl was improved, as shown by the fluorescence intensity experiment. On the whole, our findings indicate that TPs mitigate fluorosis in C57BL/6 mice by regulating OC bone resorption. Fluoride inhibits OC resorption by inhibiting ClC7 and Ostm1, whereas TPs attenuate this inhibitory effect of fluoride.
Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Fluorose Dentária/genética , Proteínas de Membrana/genética , Polifenóis/farmacologia , Chá/química , Animais , Biomarcadores , Peso Corporal/efeitos dos fármacos , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Osso e Ossos/patologia , Osso e Ossos/ultraestrutura , Modelos Animais de Doenças , Fluorose Dentária/metabolismo , Fluorose Dentária/patologia , Fluorose Dentária/prevenção & controle , Expressão Gênica , Homeostase , Imuno-Histoquímica , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/ultraestrutura , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologiaRESUMO
OBJECTIVE: Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances of bone metabolism in other diseases. Here, we have investigated the possibility that the rs1341239 polymorphism is associated with SF, which results from the consumption of brick tea. DESIGN: We conducted a cross-sectional study in Sinkiang, Qinghai, Inner Mongolia in China. Demography survey questionnaires were completed and physical examination and X-ray diagnoses were used to diagnose SF. Brick tea water fluoride intake (IF) and urinary fluoride (UF) were tested by an F-ion selective electrode method. A Sequenom MassARRAY system was used to determine PRL gene polymorphisms. RESULTS: Subjects who were younger than 45 years of age and carried the T allele had a significantly decreased risk of SF [OR = 0.279 (95%CI, 0.094-0.824)] compared to those carrying the homozygous G allele. This phenomenon was only observed in Kazakh subjects [OR = 0.127 (95%CI, 0.025-0.646)]. Kazakh females who carried T alleles has a decreased risk of SF [OR = 0.410 (95%CI, 0.199-0.847)]. For Kazakh subjects which IF is less than 3.5 mg/d, a decreased risk of SF was observed among the participants who carried T alleles [OR = 0.118 (95%CI, 0.029-0.472)]. Overall, subjects with 1.6-3.2 mg/L UF and carried T alleles had a significantly decreased risk of SF [OR = 0.476 (95%CI, 0.237-0.955)] compared to homozygous G allele carriers. This phenomenon was only observed in Kazakh subjects [OR = 0.324 (95%CI, 0.114-0.923)]. CONCLUSIONS: Our results suggested that the PRL rs1341239 T allele decreases the risk of brick tea SF.
Assuntos
Doenças Ósseas/induzido quimicamente , Doenças Ósseas/genética , Polimorfismo de Nucleotídeo Único , Prolactina/genética , Chá/efeitos adversos , Adulto , Idoso , Alelos , Povo Asiático/genética , Doenças Ósseas/diagnóstico por imagem , Estudos Transversais , Água Potável/análise , Feminino , Fluoretos/urina , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Chá/químicaRESUMO
The biological oxidation capacity and change of microbial community structure of typical landfill cover soil cultured in situ by methane and trichloroethylene (TCE) were studied. The rates of CH4 oxidation and TCE degradation were 0.20-0.87 Μmol·g-1 soil·h-1 and 0.009-0.013 mg·L-1·h-1 among these landfill cover soils, respectively. The activity of CH4 oxidation in Shandong landfill cover soil was higher than that in landfill cover soils sampled from Guangdong, Shanghai and Chongqing. The α-diversity and microbial community structure before and after co-metabolism degradation were then investigated in all landfill cover soils by Illumina MiSeq sequencing. The results indicated that bacterial Operational Taxonomic Units (OTUs) were assigned to 39 phyla, 85 classes and 562 genera in all the commented OTUs clustering. The dominant bacterial populations were Proteobacteria, Bacteroidetes, Chloroflexi and Acidobacteria and the sum of the proportion was over 77.4% in all landfill cover soils. In addition, total percent of γ-Protebacteria, ß--Protebacteria, α-Proteobacteria, Actinobacteria and Acidobacteria was over 26.5%. Specifically, the relative abundances of Methylophilaceae_uncultured, Anaerolineaceae_uncultured, Arthrobacter and Pseudomonas increased obviously after acclimated by TCE. These results suggested that there were co-metabolism degradation with non-methane compounds and aerobic assimilation of TCE besides the widely-agreed co-metabolism degradation by methanotrophs.
Assuntos
Metano , Microbiologia do Solo , Tricloroetileno , China , Oxirredução , Solo , Instalações de Eliminação de ResíduosRESUMO
Simulated landfill cover with real time online monitoring system was developed using cover soils. Then the system started and the concentrations of bio-gas in various depths were continuously monitored, and it was found that the system ran continually and stably after 2-3 h when methane flux changed. After that, the relationship between regularity of methane oxidation and methane flux in landfill cover was analyzed. The results indicated that concentration of oxygen decreased with increasing methane flux when the depth was deeper than 20 cm, and no obvious correlation between oxygen concentration in landfill cover surface and methane flux, however, methane oxidation rate showed positive correlation with methane flux in various depths (range of R2 was 0.851-0.999). Kinetics of CH4 oxidation in landfill cover was fitted by CH4 -O2 dual-substrate model (range of R2 was 0.902-0.955), the half-saturation constant K(m) increasing with depth was 0.157-0.729 in dynamic condition. Finally, methanotrophs community structure in original cover soil sample and that in simulated landfill cover were investigated by high-throughout sequencing technology, and the statistics indicated that the abundance and species of methanotrophs in simulated landfill cover significantly increased compared with those in original cover soil sample, and type I methanotrophs including Methylobacter and Methylophilaceae and type II methanotrophs Methylocystis were dominant species.
Assuntos
Metano/química , Microbiologia do Solo , Solo/química , Cinética , Methylococcaceae , Oxirredução , ProteobactériasRESUMO
BACKGROUND: Previous studies for non-communicable disease cotrol, including cancer, have mostly relied on health literacy in adults. However, limited studies are available for adolescents. This study aimed to assess the status and determinants of health literacy in in-school adolescents in Guangdong, China. MATERIALS AND METHODS: A total of 3,821 students aged 13-25 years were selected by multi-stage cluster sampling. After the questionnaire of health literacy was answered, the total scores for health knowledge (18 questions), skills (5 questions) and behaviors (14 questions) were determined. The total scores for health literacy and each subscale were recoded into adequate and inadequate subgroups, and logistic regression models were used to identify factors associated with each outcome variable. RESULTS: The prevalence of adequate health literacy was 14.4%, and the prevalences for adequate knowledge, skills and behavior were 22.4%, 64.7% and 6.6%, respectively. Students coming from prestigious schools and having parents with higher education had higher odds of having adequate knowledge, skills and behaviors. Female students had higher odds of having adequate knowledge and behaviors. Students in grade 7-8 had higher odds of having adequate knowledge and skills. The health knowledge was positive associated with health skills (odds ratio [OR]=2.1, 95% confidence interval [CI] 1.7-2.5) and behaviors (OR=3.0, 95% CI 2.3-4.0), and health skills were positive associated with health behaviors (OR=2.6, 95% CI 1.8-3.8). CONCLUSIONS: Further efforts should be made to increase adolescents' health knowledge and behaviors, especially for low grade and male students in non-prestigious schools.
Assuntos
Comportamentos Relacionados com a Saúde/etnologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Letramento em Saúde/normas , Adolescente , Adulto , Fatores Etários , China , Estudos Transversais , Escolaridade , Feminino , Letramento em Saúde/tendências , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fatores de Risco , Fatores Sexuais , Classe Social , Inquéritos e Questionários , Adulto JovemRESUMO
Using universal primer Tyl-copia retrotransposon RT, the conserved reverse transcriptase domain of about 260 bp was amplified by RT-PCR from the Dendrobium officinale which induced by 100 micromol x L(-1) abscisic acid (ABA), indicating these retrotransposons activated by 100 micromol x L(-1) ABA. The amplicons were recovered and cloned,then sequenced and analyzed by related bioinformatics software. Forty-two Ty1-copia like retrotransposon RT transcriptionally activated were obtained with high heterogeneity. The length of these sequences varied from 247 to 266 bp, and was rich in AT and homology ranged from 46.3% to 98.9%. The same to Ty1-copia like retrotransposon RT of genome, different c/s-acting regulatory elements induced by stress conditions and the starting transcription signals, corresponding to CAAT box, TATA box conserved sequences and some other regulatory elements. The c/s-acting regulatory elements induced by stress conditions of reverse transcriptase transcriptionally activated of Tyl-copia retrotransposons were significantly increased than that of Ty1-copia like retrotransposon RT of genome. When being translated into amino acids, fifteen sequences presented stop codon mutation, nineteen sequences presented frameshift mutation, and all sequences presented conserved sequence "SLYGKQ" mutation. Five categories were identified through phylogenic analysis after alignment analyses of their amino acid sequences, and with Ty1-copia like retrotransposon RT of genome having low homology, which indicated that reverse transcriptase transcriptionally activated of Ty1-copia retrotransposons which induced by ABA had Significantly differences with Ty1-copia like retrotransposon RT of genome.
Assuntos
Ácido Abscísico/farmacologia , Dendrobium/genética , Retroelementos/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Sequência de Aminoácidos , Dendrobium/efeitos dos fármacos , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de AminoácidosRESUMO
Using universal primer Ty1-copia retrotransposon RT,43 Ty1-copia like retrotransposon RT with high heterogeneity, stop codon mutation and frameshift mutation were amplified by PCR from genomic DNA of Zhejiang Lin'an (C15) and Yunnan Guangnan (A39) of Dendrobium officinale. The length of these sequences varied from 260 to 266 bp, and was rich in AT and consistency ranged from 47.1% to 97.7%. Different c/s-acting regulatory elements induced by low temperature, heat, light, all kinds of plant growth regulating substances and the starting transcription signals, corresponding to CAAT box, TATA box conserved sequences and some other regulatory elements. When being translated into amino acids, ten sequences presented stop codon mutation, five sequences presented frameshift mutation, and thirty-seven sequences presented conserved sequence "SLYGKQ" mutation. Six categories were identified through phylogenic analysis after alignment analyses of their amino acid sequences, and with other plants (eg. Triticum aestivum, Eleocharis quinqueflora) having high homology, which indicated that horizontal transmission of retrotransposon occurred among the plants in the past.
Assuntos
Dendrobium/enzimologia , Dendrobium/genética , DNA Polimerase Dirigida por RNA/genética , Retroelementos/genética , Sequência de Aminoácidos , Clonagem Molecular , Sequência Conservada , DNA de Plantas/genética , Dados de Sequência Molecular , Filogenia , DNA Polimerase Dirigida por RNA/química , TATA Box/genéticaRESUMO
Arsenic trioxide (As2O3) has been recognized as a potential chemotherapeutic agent, yet the details concerning its mechanism of action in solid cancers remain undetermined. The present study assessed the role of Akt in the cell death induced by As2O3. The MTT assay showed that As2O3 suppressed the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Characteristic apoptotic changes were observed in the As2O3treated cells by Hoechst 33342 staining, and FACS analysis showed that As2O3 caused dose-dependent apoptotic cell death. As2O3 activated caspase-3 and -9, and PARP cleavage in a dose-dependent manner. Compromised mitochondrial membrane potential and an increased protein level of Bax indicated involvement of mitochondia. As2O3 decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3ß (Ser9), suggesting that As2O3 inactivated Akt kinase. In addition, LY294002 (a PI3 kinase inhibitor) augmented the apoptosis induced by As2O3. These results demonstrated that inhibition of PI3K/Akt signaling was involved in As2O3-induced apoptosis of gastric cancer SGC-7901 cells.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Mitocôndrias/efeitos dos fármacos , Óxidos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Trióxido de Arsênio , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-aktRESUMO
This paper aims to achieve Bootstraping in hierarchical data and to provide a method for the estimation on confidence interval(CI) of intraclass correlation coefficient(ICC).First, we utilize the mixed-effects model to estimate data from ICC of repeated measurement and from the two-stage sampling. Then, we use Bootstrap method to estimate CI from related ICCs. Finally, the influences of different Bootstraping strategies to ICC's CIs are compared. The repeated measurement instance show that the CI of cluster Bootsraping containing the true ICC value. However, when ignoring the hierarchy characteristics of data, the random Bootsraping method shows that it has the invalid CI. Result from the two-stage instance shows that bias observed between cluster Bootstraping's ICC means while the ICC of the original sample is the smallest, but with wide CI. It is necessary to consider the structure of data as important, when hierarchical data is being resampled. Bootstrapping seems to be better on the higher than that on lower levels.
Assuntos
Modelos Estatísticos , Análise de Regressão , Projetos de Pesquisa , Intervalos de ConfiançaRESUMO
OBJECTIVE: To observe the effects of beta3-adrenergic receptor(beta3-AR) antagonist on myocardial uncoupling protein 2 (UCP2) expression and energy metabolism in chronic heart failure rats. METHODS: Seven weight-matched normal adult rats (control group), 18 isoproterenol (ISO) induced heat failure (HR) rats (ISO group) and 21 ISO induced heart failure rats but received specific beta3-AR inhibitor SR59230A (ISO+ SR59230A group) for 6 weeks were included in this research. At the end of the study, echocardiography was performed, the ratio of left ventricular weight and body weight (LVW/BW) was calculated. The expression of beta3-AR ad UCP2 mRNA in myocardium were detected by reverse transcription-polymerase chain reaction (RT-PCR), the UCP2 protein in myocardium were detected by Western blot. The myocardial contents of creatine phosphate (PCr) and adenosine triphosphate (ATP) were measured by high performance liquid chromatography (HPLC). RESULTS: Compared with control group, the cardiac function was significantly reduced and myocardial beta3-AR mRNA significantly increased, UCP2 mRNA and protein were also significantly increased in ISO group, this change could be attenuated by the treatment with SR59230A, and the expression of myocardial UCP2 protein negatively correlated with the ratio of PCr/ATP. CONCLUSION: In the chronic stage of HF, the expression of UCP2 increases, which causes myocardial energy shortage, SR59230A improves myocardia energy efficiency and cardiac function by means of suppressing the expression of UCP2.
Assuntos
Antagonistas Adrenérgicos/farmacologia , Insuficiência Cardíaca/metabolismo , Canais Iônicos/metabolismo , Proteínas Mitocondriais/metabolismo , Miocárdio/metabolismo , Animais , Metabolismo Energético , Masculino , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 3/metabolismo , Proteína Desacopladora 2RESUMO
BACKGROUND: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 gene and risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory. METHODS: We performed a meta-analysis in the present study using STATA 11.0 software to clarify any associations. Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 published studies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. RESULTS: No significant associations were observed between Arg399Gln and DTC risk in all genetic models within the overall and subgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphism was associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed to DTC susceptibility in Caucasians. CONCLUSIONS: Our meta-analysis suggests that XRCC1 Arg194Trp may be a risk factor for DTC development.
Assuntos
Adenocarcinoma/etiologia , Diferenciação Celular , Proteínas de Ligação a DNA/genética , Polimorfismo Genético/genética , Neoplasias da Glândula Tireoide/etiologia , Predisposição Genética para Doença , Humanos , Prognóstico , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XAssuntos
Comportamentos Relacionados com a Saúde , Modelos Teóricos , Adolescente , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In order to accurately investigate the preclinical pharmacokinetics of (R)-(+)-rabeprazole sodium injection, a reliable high-performance liquid chromatography (HPLC) method was developed using a Chiral-AGP column to prove that there is no chiral bioconversion of (R)-(+)-rabeprazole to (S)-(-)-rabeprazole in beagle dogs after single intravenous administration of (R)-(+)-rabeprazole sodium injection. An HPLC-tandem mass spectrometry (HPLC-MS/MS) method for analysis of (R)-(+)-rabeprazole was developed and validated, and used to acquire the pharmacokinetic parameters in beagle dogs. (R)-(+)-Rabeprazole and internal standard omeprazole were extracted from plasma samples by protein precipitation and separated on a C18 column using methanol-5 mm ammonium acetate as mobile phase. Detection was performed using a turbo-spray ionization source and mass spectrometric positive multi-reaction monitoring mode. The linear relationship was achieved in the range from 2.5 to 5000 ng/mL. The method also afforded satisfactory results in terms of sensitivity, specificity, precision, accuracy and recovery as well as the stability of the analyte under various conditions, and was successfully applied to a preclinical pharmacokinetic study in beagle dogs after single intravenous administrations of (R)-(+)-rabeprazole sodium injection at 0.33, 2 and 6 mg/kg.
Assuntos
Antiulcerosos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Rabeprazol/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Antiulcerosos/química , Cães , Feminino , Limite de Detecção , Masculino , Rabeprazol/química , EstereoisomerismoRESUMO
In order to study the molecule mechanism of the differential expression in Dendrobium officinale under low temperature, the high cold resistance germplasms were used for constructing the RNA pools. SCoT markers were used to analyze the different cDNA pools transcribed from the RNA pools. 11 transcripts derived fragments from 500 cDNA amplified bands were amplified by 64 primers, and were sorted out, cloned, sequenced and analyzed. The results showed that cDNA pools with SCoT markers could be used for differential display in D. officinale under low temperature stress. Sequence analysis indicated that the transcripts derived fragments were significantly homologous in nucleotide sequence with membrane-associated proteins, osmotic regulation protein, CBF transcriptional factor, resistance protein. One left gene segments functions were still unknown, which may be related to the cold resistant gene expression in D. officinale.