Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
1.
BMJ Open ; 12(7): e062239, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35906046

RESUMO

OBJECTIVES: We aimed to assess the associations between night-time sleep duration and fasting glucose (FG), triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio and body mass index (BMI) among adults free of type 2 diabetes (T2D) or without diagnosed T2D. DESIGN: Cross-sectional study. SETTING: Medical examination centres at six hospitals in Beijing-Tianjin-Hebei region, China. PARTICIPANTS: Participants were recruited via multistage, stratified cluster sampling. We included adults free of T2D or without diagnosed T2D who attended for physical examination and completed the validated questionnaire. 32 497 participants were included in the study, of whom 52.50% were men. PRIMARY AND SECONDARY OUTCOME MEASURES: FG, TG, HDL-C, height and weight were measured. RESULTS: Overall, 12.80% and 9.67% reported night sleep duration <7 hours and ≥9 hours, respectively; 6.91% had elevated FG and 3.57% had undiagnosed T2D. Sleep duration had an independent, U-shaped associated with FG (ß1 (linear term)=-0.111, p=0.047; ß2 (quadratic term)=0.008, p=0.026) with 6.9 hours of sleep associated with the lowest FG and a negative association with BMI (ß=-0.154, p<0.001). BMI mediated a U-shaped association of sleep duration with TG/HDL-C (ß1=-0.040, p=0.017; ß2=0.003, p=0.023). CONCLUSIONS: Both short and long night-time sleep was associated with elevated FG, and short sleep duration was associated with increased BMI. BMI mediated a U-shaped association between sleep duration and TG/HDL-C.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , China/epidemiologia , HDL-Colesterol , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Jejum , Feminino , Glucose , Humanos , Masculino , Sono , Triglicerídeos
2.
Biomed Environ Sci ; 34(10): 803-813, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34782046

RESUMO

OBJECTIVE: The study aims to predict 10-year cardiovascular disease (CVD) risk and explore its association with sleep duration among Chinese urban adults. METHODS: We analyzed part of the baseline data of a cohort that recruited adults for health screening by cluster sampling. The simplified Pittsburgh Sleep Quality Index (PSQI) and Framingham 10-year risk score (FRS) were used to measure sleep duration and CVD risk. Demographic characteristics, personal history of chronic diseases, lifestyle factors were collected using a questionnaire. Height, weight, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were also measured. Multiple logistic regression models were performed to explore the association of sleep duration with the predicted CVD risk. RESULTS: We included 31, 135 participants (median age 44 years, 53.02% males) free of CVD, cerebral stroke, and not taking lipid-lowering agents. Overall, 14.05%, and 25.55% of participants were at medium and high predicted CVD risk, respectively. Short sleep was independently associated with increased odds of medium to high risk of predicted 10-year CVD among males ( OR = 1.10; 95% CI: 1.01-1.19) and increased odds of medium to high and high risk of predicted 10-year CVD among females ( OR = 1.23; 95% CI: 1.08-1.40; OR = 1.27; 95% CI: 1.11-1.44). In contrast, long sleep had no association with cardiovascular risk. CONCLUSION: A substantial number of adults free of CVD were at high 10-year CVD risk. Short sleep was associated with increased odds of predicted CVD risk.


Assuntos
Doenças Cardiovasculares/epidemiologia , Qualidade do Sono , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
3.
Anim Biosci ; 34(4): 680-691, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33254361

RESUMO

OBJECTIVE: This study was conducted to investigate the effect of fermented cottonseed meal (FCSM) on growth performance, carcass traits, and fat deposition in white-feather broiler chickens. METHODS: A total of 480 male one-day-old white-feather broiler chickens were selected randomly and divided into four groups with six replicates of 20 chickens in each. The experimental chickens were fed diets including 3%, 6%, or 9% FCSM fermented by Candida tropicalis until 42 days old. In the experiment, the chickens of the control group were fed soybean meal. RESULTS: FCSM supplementation linearly decreased the feed conversion ratio from d 15 to 21 and d 36 to 42, respectively (p<0.05). The percentage of carcass and semi-eviscerate increased in response to dietary FCSM supplementation at d 21 (p<0.05). The percentage of eviscerated and semi-eviscerate of 3FCSM was higher than that in other groups at d 35 (p<0.05). At the age of 42 d, the percentage of carcass increased in a quadratic way among increasing FCSM in diets (p<0.05). The subcutaneous fat thickness linearly decreased with the increasing levels of FCSM at d 21 (p<0.05). Gompertz and Logistic functions provided a better fit on abdominal fat and subcutaneous fat, respectively. The best fitted equation predicted that the maximum growth rate of abdominal fat weight and subcutaneous fat thickness occurred at d 28. FCSM had no significant effects on the shape of growth curve of abdominal fat weight and subcutaneous fat thickness, but reduced the height of the curve. Birds receiving the 6FCSM diet for 21 d had smaller adipocyte surface and lower serum glucose as well as triglyceride concentration. CONCLUSION: FCSM is beneficial for broiler chickens as it positively affects their growth and carcass in addition to altering their fat deposition.

4.
J Hazard Mater ; 402: 123452, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32688193

RESUMO

Human exposure to drinking water disinfection by-products (DBPs) is potentially linked to high blood pressure (BP), which may be associated with abnormal platelet activation. This study investigated whether the relationship between DBP exposure with platelet change was mediated by BP. DBP biomarkers, such as urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), BP and platelet indices from 505 adults from a hospital in Shijiazhuang, China were measured. The cross-sectional associations among DCAA and TCAA exposure, BP and platelet indices were explored through multivariable linear regressions, and the mediation effect of BP was evaluated using the Sobel-Goodman test. We observed that DCAA and TCAA were positively associated with systolic BP (all p for trends < 0.01), which was positively associated with platelet count (PLC) (p for trend < 0.05). Mediation analysis indicated that systolic BP fully mediated the associations of DCAA and TCAA with PLC. When BP was controlled, a previously inverse significant relation between DCAA and platelet distribution width (PDW) remained significant (p < 0.05). Obtained results suggested that exposure to DCAA may contribute to decreased PDW in humans. Systolic BP is a possible mediator of the association between DCAA exposure and PLC. TCAA may indirectly positively affect PLC by increasing systolic BP.


Assuntos
Ácido Dicloroacético , Ácido Tricloroacético , Adulto , Pressão Sanguínea , China , Estudos Transversais , Humanos , Ácido Tricloroacético/toxicidade
5.
Mol Pharm ; 17(5): 1685-1696, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32191042

RESUMO

As a cell-penetrating peptide, polyarginine is widely used in drug delivery systems based on its membrane permeation ability. Previously, we developed the mPEG-PLA-b-polyarginine(R15) triblock copolymer, which exhibited a high siRNA delivery efficiency both in vitro and in vivo. As a continued effort, here the amphiphilic diblock polymer PCL-R15 was synthesized as a simplified model to further elucidate the structure-activity relationship of arginine-based amphiphilic polymers as siRNA delivery systems, and the cellular trafficking mechanisms of the PCL-R15/siRNA nanoplexes were investigated to understand the interaction patterns between the nanoplexes and cells. Compared to the R15/siRNA complexes, the introduction of PCL moiety was found to result in the stronger interactions with cells and the enhanced transfection efficiency after the formation of condensed nanoplexes. Caveolae-mediated endocytosis and clathrin-mediated endocytosis were major routes for the internalization of PCL-R15/siRNA nanoplexes. The intracellular release of siRNA from nanoplexes was confirmed by fluorescence resonance energy transfer assay. It was also noticed that the internalized PCL-R15/siRNA nanoplexes were transported through digestive routes and trapped in lysosomes, which may be the bottleneck for efficient siRNA delivery of PCL-R15/siRNA nanoplexes. This study investigated the relationship between the polymer structure of PCL-R15 and the cellular interaction patterns, which may render implications on the rational design of polyarginine-based siRNA delivery systems.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/química , Peptídeos/química , Poliésteres/química , RNA Interferente Pequeno/administração & dosagem , Transporte Biológico , Células HeLa , Humanos , Nanopartículas/metabolismo , Poliésteres/metabolismo , RNA Interferente Pequeno/química
6.
Environ Sci Pollut Res Int ; 26(12): 12227-12236, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30835062

RESUMO

Electronic waste (e-waste) recycling has proven to be a significant source of phthalate (PAE) contamination in the environment. A detailed investigation was conducted to understand the concentration, distribution, profile and possible source of PAEs in residential and agricultural soils from Guiyu, Shantou, China, the largest e-waste processing and recycling areas in the world. Sixteen PAEs were analysed in 46 surface soil samples from three different sampling areas in terms of individual and total concentrations, together with pH and soil organic matter. High concentrations of the total PAEs were found in residential area A (more than 20,000 ng g-1), revealing a clear urban pulse, whereas in residential area B and agricultural areas, concentrations were lower than 10,000 ng g-1. The dominant PAEs were bis (2-nbutoxyethyl) phthalate, bis (4-methyl-2-pentyl) phthalate and dicyclohexyl phthalate. These PAEs were high-molecular weight PAEs (alkyl chains ≥ 6 carbons) and mainly derived from polyvinyl chloride commonly used in electrical and electronic equipment, indicating a distinctive composition in relation to the e-waste area. Three individual and the total PAEs exhibited significant positive correlations with pH. Principal component analysis indicated that PAEs were mainly distributed in three groups according to the alkyl chain length and potential source. This study showed that the informal e-waste recycling has already introduced PAEs into surrounding areas as a pollutant which should draw more attention and regulatory control.


Assuntos
Resíduo Eletrônico/análise , Monitoramento Ambiental , Ácidos Ftálicos/análise , Poluentes do Solo/análise , Agricultura , Carbono/análise , China , Ésteres/análise , Reciclagem , Solo/química
7.
Ying Yong Sheng Tai Xue Bao ; 28(12): 3891-3898, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29696884

RESUMO

The research selected the alpine meadow located in the northeastern margin of the Qinghai-Tibet Plateau to study the changes of vegetation community and soil properties under different grazing intensities, as well as the quantitative relation between the distribution patterns of plant species and the physical and chemical properties of soil. The results showed that the grazing caused the differentiation of the initial vegetation community with the dominant plants, Elymus nutans and Stipa grandis. In the plots with high and low grazing intensities, the dominant plants had changed to Kobresia humilis and Melissitus ruthenica, and E. nutans and Poa crymophila, respectively. With the increase of grazing intensity, the plant richness, importance value and biomass were significantly decreased. The sequence of plant species importance value in each plot against grazing intensity could be fitted by a logarithmic model. The number of required plant species was reduced while the importance value of the remaining plant species accounted for 50% of the importance value in the whole vegetation community. The available P, available K, soil compaction, soil water content, stable infiltration rate and large aggregate index were significantly changed with grazing intensity, however, the changes were different. The CCA ordination showed that the soil compaction was the key factor affecting the distribution pattern of the plant species under grazing. The variance decomposition indicated that the soil factors together explained 30.5% of the distribution of the plant species, in particular the soil physical properties alone explained 22.8% of the distribution of the plant species, which had the highest rate of contribution to the plant species distribution. The soil physical properties affected the distribution pattern of plant species on grazed alpine meadow.


Assuntos
Pradaria , Solo , Biomassa , Ecossistema , Poaceae , Tibet
8.
Ying Yong Sheng Tai Xue Bao ; 28(6): 1824-1832, 2017 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-29745144

RESUMO

The research selected the plots of six grazing intensities in an alpine meadow in north-eastern Tibet Plateau in four years (2012-2015) and studied the relation between ten species diversity indexes, including two measured indexes (Richness and Abundance) in field and two indexes of each dominance, evenness, richness, integrated indexes, and grazing intensity as well as grazing time aiming at scientific selection of biodiversity index under grazing disturbance. The results indicated that the abundance was a better index than importance value to calculate biodiversity level because it was more sensitive to grazing disturbance. Dominance indexes, including Berger-Parker and Dominance, were not sensitive to grazing intensity and grazing time because they could not clarify the effect of grazing disturbance on dominant species in plant community. Evenness indexes, including Equitability and Evenness, had not relation with grazing intensity, however, the evenness index had a negative correlation with grazing time and it was not influenced by occasional species as well as the variation coefficient of species abundance. Hereby, the evenness index could be chosen for studying evenness change at temporal scale. Richness indexes, including Menhinick and Margalef, had no relation with grazing time, however, the Margalef index had a positive correlation with grazing intensity and the index was not influenced by occasional species. Integrated index, including Shannon and Simpson indexes, had no relation with grazing intensity, however, the Shannon index had a significant positive correlation with species richness and abundance and the index was not influenced by occasional species, and it significantly increased along grazing time. Hereby, Shannon index could be used as an index of studying plant species diversity in long-term. In ten diversity indexes, only the measured indexes in field, including richness and abundance, were signifi-cantly negatively correlated with grazing intensity, and positively correlated with grazing time, and the two indexes were not influenced by occasional species. Hereby, the combination of species richness and abundance mea-sured in field could be considered as the most important indexes for studying plant species diversity under grazing disturbance. Besides, the selection of biodiversity indexes must consider the spatial-temporal feature of grazing, diversity components and research purpose.


Assuntos
Biodiversidade , Plantas , Tibet
9.
Ying Yong Sheng Tai Xue Bao ; 28(5): 1489-1497, 2017 May 18.
Artigo em Chinês | MEDLINE | ID: mdl-29745184

RESUMO

For understanding the effect of aspect and altitude of hill on soil moisture and temperature as well as the vegetation community, we selected an alpine meadow located on a hill in north-eastern Tibet Plateau as our study area. Data on soil moisture and temperature, as well as plant distribution pattern in this mountain ecosystem were collected. We used regression analysis, CCA ordination and variance decomposition, to determine the impacts of the key factors (aspect, altitude, soil temperature and moisture) on plant diversity distribution in 189 sample sites of the hill. The results showed that the plant diversity of shady aspect and bottomland was highest and lowest, respectively. The plant diversity of the shady aspect and on the ridge of the hill increased initially and then decreased with the increasing altitude, but the plant diversity of the sunny aspect increased with the increasing altitude. At 0-30 cm soil layer, the soil temperature of the sunny aspect was higher than that of other aspects, but the soil temperature at 0-20 cm soil layer did not change with the increa-sing altitude. The soil moisture of shady aspect was higher than that of other aspects, and increased with the increasing altitude. The aspect and altitude explained 100% of soil temperature changes and 51.8% of soil moisture variation. Aspect alone explained 72.2% of soil temperature variation and altitude alone explained 51.8% of soil moisture variation, which had the highest contribution rate individually. Most plants were distributed on the shady aspect and on the ridge, and at medium altitude. Sedges mainly grew on the shady aspect, while Gramineae grew on the sunny aspect, the ridge was an ecotone. Cyperaceae, Gramineae and Leguminosae were mainly distributed in low altitude zone. Hill aspect and altitude totally explained 28.6% of plant abundance variation, hill aspect alone explained 19.9% of plant abundance variation. The management of grassland production and ecological restoration in alpine meadow ecosystem should consider the effect of landform on soil and vegetation, and the hill aspect should be priority factor instead of altitude when planning management interventions.


Assuntos
Altitude , Dispersão Vegetal , Solo , Ecossistema , Pradaria , Temperatura , Tibet
10.
J Control Release ; 235: 99-111, 2016 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-27242198

RESUMO

In our previous study, a H-shape gemini-like cationic lipid (ssGLCL, formerly named as CLD), composed of two hydrophilic lysine heads and two hydrophobic oleyl alcohol tails with a bridge of the redox-active disulfide-bond, had been synthesized and used as a nanocarrier for delivering small interfering RNAs (siRNAs) into cells. In order to further elucidate the role of disulfide (-S-S-) bridge on the activity of ssGLCL based siRNA delivery, a comparable ccGLCL bridged with a non-reducible carbon-carbon bond was synthesized and used as control in this study. Both two H-shape GLCL molecules could individually self-assemble into cationic nanoparticles in water phase and complex with negatively-charged siRNA into nanoplexes with particle size of ~200nm and zeta potential of ~ +30mV, and exhibit effective siRNA delivery both in vitro and in vivo. Investigation of internalization pathway displayed that both ssGLCL/siRNA and ccGLCL/siRNA nanoplexes were predominantly internalized into MCF-7 cells by the clathrin-mediated endocytosis pattern. Although a lower cellular uptake of siRNA was found in the human breast cancer MCF-7 cells, the ssGLCL/siRNA nanoplexes could exhibit similar or even stronger down-regulation effects on the targeted EGFR mRNA and protein in MCF-7 cells when compared to the ccGLCL/siRNA nanoplexes. Furthermore, mechanistic study showed that the enhanced down-regulation effects of ssGLCL/siRNA nanoplexes on targeted mRNA and protein were probably attributed to the increased release of siRNA from lysosomes to cytoplasm following the cleavage of redox-active disulfide-bridge in ssGLCL. Therefore, we believed that the redox-active H-shape ssGLCL could be a potential nanocarrier towards improving siRNA delivery.


Assuntos
Dissulfetos/química , Técnicas de Transferência de Genes , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Animais , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Eritrócitos/efeitos dos fármacos , Feminino , Inativação Gênica , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Lipídeos/química , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/química , Ratos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Am J Transl Res ; 7(10): 1724-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26692920

RESUMO

Oxidative stress plays an important role in doxorubicin (DOX)-induced cardiotoxicity. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor that orchestrates the antioxidant and cytoprotective responses to oxidative stress. In the present study, we tested whether tert-butylhydroquinone (tBHQ) could protect against DOX-induced cardiotoxicity in vivo and, if so, whether the protection was associated with the up-regulation of the Nrf2 pathway. The results showed that treatment with tBHQ significantly decreased the DOX-induced cardiac injury in wild-type mice. Moreover, tBHQ ameliorated the DOX-induced oxidative stress and apoptosis. Further studies suggested that tBHQ increased the nuclear accumulation of Nrf2 and the Nrf2-regulated gene expression, including heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxido-reductase-1 (NQO-1) expression. Knocking out Nrf2 in mice abolished the protective effect of tBHQ on the DOX-induced cardiotoxicity. These results indicate that tBHQ has a beneficial effect on DOX-induced cardiotoxicity, and this effect was associated with the enhanced expression of Nrf2 and its downstream antioxidant genes, HO-1 and NQO-1.

12.
FEMS Microbiol Lett ; 362(6)2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25667230

RESUMO

Yeast Cia2p is a component of the cytosolic Fe/S protein assembly (CIA) machinery. Initial studies of the CIA machinery were performed in yeast, but the precise role of Cia2p in this eukaryote is still unknown. We report that CIA2 deficiency results in impaired oxidative stress response, as evidenced by increased sensitivity to the oxidant cumene hydroperoxide (CHP), impaired activities of superoxide dismutases and aconitase and decreased replicative lifespan in the mutants. Moreover, intracellular reactive oxygen species levels were significantly increased in CIA2-deficient cells after treatment with CHP. We also show that CIA2-deficient cells display an increased resistance to tunicamycin-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulated splicing of the mRNA of HAC1, which encodes a functional transcription factor that regulates the transcription of unfolded protein response (UPR) target genes, suggesting enhanced intracellular UPR activity. Furthermore, the transcription of several canonical UPR target genes is strongly induced in CIA2-deficient cells as compared with wild-type controls. Taken together, these results suggest the involvement of Cia2p in oxidative and ER stress responses in yeast.


Assuntos
Estresse do Retículo Endoplasmático , Estresse Oxidativo , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/metabolismo , Resposta a Proteínas não Dobradas , Fatores de Transcrição de Zíper de Leucina Básica/genética , Derivados de Benzeno/farmacologia , Citoplasma/genética , Citoplasma/fisiologia , Mutação , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Transdução de Sinais , Fatores de Transcrição , Tunicamicina/farmacologia , Resposta a Proteínas não Dobradas/genética , Regulação para Cima
14.
BMJ Open ; 4(7): e005202, 2014 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-25059970

RESUMO

INTRODUCTION: Bone metastasis (BM) in patients with primary lung cancer poses a serious health problem. Numerous risk factors have been hypothesised to predict BM in these patients, but research studies are of mutable quality, and may not be of value in clinical evaluation. METHODS AND ANALYSIS: We will search a number of electronic databases including PubMed, MEDLINE, Web of Science, EMBASE, the Cochrane Library (Cochrane Database of Systematic Reviews) and the Cochrane Central Register of Controlled Trials (CENTRAL). We will carry out a secondary search for articles from references of included articles (from January 1990 to June 2014). Primary and secondary outcomes will be BM and skeletal-related events information. We will summarise the effect estimates of risk factors and use random-effect models to pool the estimates, if the outcomes and characteristics in studies are comparable. The quality of the study will be assessed using the Newcastle-Ottawa Scale and the Cochrane Collaboration tool. TRIAL REGISTRATION NUMBER: CRD42013003744.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Pulmonares/patologia , Neoplasias Ósseas/epidemiologia , Humanos , Projetos de Pesquisa , Fatores de Risco , Revisões Sistemáticas como Assunto
15.
Biomaterials ; 35(18): 5028-38, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24680191

RESUMO

A somatostatin analog, vapreotide (VAP), can be used as a ligand for targeting drug delivery based on its high affinity to somatostatin receptors (SSTRs), which is overexpressed in many tumor cells. RNA interference plays an important role on downregulation of vascular endothelial growth factor (VEGF), which is important for tumor growth, progression and metastasis. To improve tumor therapy efficacy, the vapreotide-modified core-shell type nanoparticles co-encapsulating VEGF targeted siRNA (siVEGF) and paclitaxel (PTX), termed as VAP-PLPC/siRNA NPs, were developed in this study. When targeted via somatostatin receptors to tumor cells, the VAP-PLPC/siRNA NPs could simultaneously delivery siVEGF and PTX into cells and achieve a synergistic inhibition of tumor growth. Interestingly, in vitro cell uptake and gene silencing experiments demonstrated that the targeted VAP-PLPC/siRNA NPs exhibited significant higher intracellular siRNA accumulation and VEGF downregulation in human breast cancer MCF-7 cells, compared to those of the non-targeted PEG-PLPC/siRNA NPs. More importantly, in vivo results further demonstrated that the targeted VAP-PLPC/siRNA NPs had significant stronger drug distribution in tumor tissues and tumor growth inhibition efficacy via receptor-mediated targeting delivery, accompany with an obvious inhibition of neovascularization induced by siVEGF silencing. These results suggested that the co-delivery of siRNA and paclitaxel via vapreotide-modified core-shell nanoparticles would be a promising approach for tumor targeted therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Terapia de Alvo Molecular , Nanopartículas/química , Paclitaxel/farmacologia , RNA Interferente Pequeno/genética , Somatostatina/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Neoplasias da Mama/terapia , Ciclo Celular/efeitos dos fármacos , Regulação para Baixo , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Somatostatina/metabolismo , Somatostatina/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Mech Ageing Dev ; 138: 53-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24486555

RESUMO

Saccharomyces cerevisiae Nar1p is an essential Fe/S protein that exhibits striking similarity to bacterial iron-only hydrogenases. Nar1p is required for the maturation of cytosolic and nuclear, but not of mitochondrial Fe/S proteins, and plays a role in modulating sensitivity to oxygen in both yeast and Caenorhabditis elegans through unknown mechanisms. Here we report that Nar1 deficiency results in shortened lifespan and sensitivity to paraquat that is rescued by increased expression of mitochondrial superoxide dismutase. These data suggest that Nar1p promotes protection against oxidative stress and define a new role for Nar1p in promoting replicative lifespan.


Assuntos
Hidrogenase , Proteínas Ferro-Enxofre , Paraquat , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae , Animais , Citosol/metabolismo , Herbicidas/metabolismo , Herbicidas/farmacologia , Hidrogenase/metabolismo , Proteínas Ferro-Enxofre/deficiência , Proteínas Ferro-Enxofre/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Paraquat/metabolismo , Paraquat/farmacologia , Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/ultraestrutura , Superóxido Dismutase/metabolismo , Fatores de Tempo
17.
Biomaterials ; 35(6): 2066-78, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24315577

RESUMO

Our previous study had reported that cholesterol-grafted poly(amidoamine) (rPAA-Chol polymer) was able to self-assemble into cationic nanoparticles and act as a potential carrier for siRNA transfection. In this study, the core-shell type lipid/rPAA-Chol hybrid nanoparticles (PEG-LP/siRNA NPs and T7-LP/siRNA NPs) were developed for improving in vivo siRNA delivery by modifying the surface of rPAA-Chol/siRNA nanoplex core with a lipid shell, followed by post-insertion of polyethylene glycol phospholipid (DSPE-PEG) and/or peptide (HAIYPRH, named as T7) modified DSPE-PEG-T7. The integrative hybrid nanostructures of LP/siRNA NPs were evidenced by dynamic light scattering (DLS), confocal laser scanning microscope (CLSM), cryo-transmission electron microscope (Cryo-TEM) and surface plasmon resonance (SPR) assay. It was demonstrated that the T7 peptide modified LP/siRNA NPs (T7-LP/siRNA NPs) exhibited uniform and spherical structures with particle size of 99.39 ± 0.65 nm and surface potential of 42.53 ± 1.03 mV, and showed high cellular uptake efficiency and rapid endosomal/lysosomal escape ability in MCF-7 cells. Importantly, in vitro gene silencing experiment demonstrated that both of pegylated and targeted LP/siEGFR NPs exhibited significantly stronger downregulation of EGFR protein expression level in MCF-7 cells, compared to that of the physical mixture of siRNA lipoplexes and rPAA-Chol/siRNA nanoplexes. In vivo tumor therapy on nude mice bearing MCF-7 tumors further confirmed that the targeted T7-LP/siEGFR NPs exhibited the greatest inhibition on tumor growth via transferrin receptor-mediated targeting delivery, without any activation of immune responses and significant body weight loss following systemic administration. These findings indicated that the core-shell type T7-LP/siRNA nanoparticles would be promising siRNA delivery systems for in vivo tumor-targeted therapy.


Assuntos
Nanopartículas/química , Polímeros/química , RNA Interferente Pequeno/química , Animais , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Citometria de Fluxo , Humanos , Células MCF-7 , Camundongos , Microscopia Confocal , Polietilenoglicóis/química , RNA Interferente Pequeno/fisiologia , Ressonância de Plasmônio de Superfície
18.
Environ Toxicol Pharmacol ; 36(3): 759-68, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23958968

RESUMO

As an important environmental pollutant, cadmium (Cd) can lead to serious renal damage. Grape seed procyanidins extract (GSPE), a biological active component of grape seed, has been shown to possess antioxidative effects. Here, we assessed the protective effect of GSPE on Cd-induced renal damage using animal experiment. After 30 days, the oxidative damage of kidney was evaluated through measurement of superoxide dismutase (SOD), glutathione peroxidation (GSH-Px) and malondialdehyde (MDA). Since, oxidative stress could lead to apoptosis, the renal apoptosis was measured using flow cytometer. Moreover, the expression of apoptosis-related protein Bax and Bcl-2 was analyzed by immunohistochemistry and Western blot. The results showed that Cd led to the decrease of SOD and GSH-Px activities, and the increase of MDA level, induced renal apoptosis. However, the coadministration of GSPE attenuated Cd-induced lipid peroxidation, and antagonized renal apoptosis, probably associated with the expression of Bax and Bcl-2. These data suggested that GSPE has protective effect against renal oxidative damage induced by Cd, which provide a potential natural chemopreventive agent against Cd-poisoning.


Assuntos
Antioxidantes/farmacologia , Biflavonoides/farmacologia , Intoxicação por Cádmio/prevenção & controle , Catequina/farmacologia , Nefropatias/patologia , Rim/patologia , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Vitis/química , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Biflavonoides/química , Western Blotting , Peso Corporal/efeitos dos fármacos , Intoxicação por Cádmio/patologia , Catequina/química , Citometria de Fluxo , Glutationa Peroxidase/metabolismo , Imuno-Histoquímica , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Malondialdeído/metabolismo , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/química , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Sementes/química , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/biossíntese
19.
Artigo em Chinês | MEDLINE | ID: mdl-22931813

RESUMO

OBJECTIVE: To study the effects of low pre-pregnant lead exposure level on the mobilization of lead and calcium in maternal skeleton during gestation and lactation in mice. METHODS: Seventy Kunming female mice were randomly divided into the lead exposure or control groups, 36 mice were exposed to lead by drinking water (50 mg/L) and 36 mice were exposed to deionized water for 4 weeks. The levels of calcium and lead in blood and femurs were measured on the 1st, 7th and 14th days during gestation and on the 1st,10th and 21st days during lactation with atomic absorption spectrophotometry using a heated graphite atomizer or flame atomic absorption spectrophotometry. RESULTS: As compared with the pre-pregnant, at the end of lactation in exposure group the levels of calcium in blood and bones significantly decreased 18.5% and 17.75%, respectively, the levels of lead in blood significantly increased 65.22% and the levels of lead in bones significantly decreased 28.45% (P < 0.05). There was a significant negative correlation between the blood lead level and the bone lead level during gestation and lactation in exposure group (r = -0.904, P < 0.01). There were significant differences of lead and calcium levels during the gestation and lactation between exposure group and control group (P < 0.05). CONCLUSION: The lead mobilization in maternal bone occurred during gestation and lactation in mice, which could be accelerated by the low pre-pregnant lead exposure.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Osso e Ossos/metabolismo , Cálcio/sangue , Cálcio da Dieta , Feminino , Lactação , Chumbo/sangue , Camundongos , Camundongos Endogâmicos , Gravidez
20.
Artigo em Chinês | MEDLINE | ID: mdl-22096849

RESUMO

OBJECTIVE: To investigate the effects of the cadmium chloride on the DNA damage and the expression of the gadd153 and gadd45beta promoter and mRNA in HepG2 cells. METHODS: DNA damage induced by cadmium chloride was detected by comet assay. The plasmids (pGADD153-Luc and pG45-Luc) containing DNA damage and repair inducible gene 153 and 45 (gadd153 and gadd45beta) promoter and luciferase and gadd45beta reporter gene were constructed. The activity of gadd153 and gadd45beta promoter were represented by the luciferase activity, the inducible luciferase activities was detected by bioluminescence. The expression of gadd153 and gadd45beta mRNA was detected by RT-PCR. RESULTS: The results of comet assay indicated that Olive Tail Moment induced by the cadmium chloride increased significantly at the dose of 100, 300 micromol/L, compared with the control (P < 0.05). The luciferase activity analysis showed that the expression levels of gadd153 promoter increased significantly in 1, 5, 10 micromol/L treatment group, compared with the control (P < 0.05). The expression levels of gadd45beta promoter in 5, 10 micromol/L treatment group were significantly higher than that in control group (P < 0.05). The expression levels of gadd153 mRNA induced by cadmium chloride at the doses of 1, 5, 10 micromol/L and the expression levels of gadd45beta mRNA induced at the doses of 5, 10 micromol/L were significantly higher than thoae in control group (P < 0.05). CONCLUSION: The cadmium chloride can induce the DNA damage and increase the expression levels of the gadd153 and gadd45beta promoters in HepG2 cells.


Assuntos
Antígenos de Diferenciação/genética , Cloreto de Cádmio/toxicidade , Dano ao DNA/efeitos dos fármacos , Fator de Transcrição CHOP/genética , Ensaio Cometa , Genes Reporter , Células Hep G2 , Humanos , Plasmídeos , Regiões Promotoras Genéticas , RNA Mensageiro/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA