RESUMO
BACKGROUND: A meta-analysis of polymorphism C677T (rs1801133) of the methylene tetrahydrofolate reductase (MTHFR) gene as a potential risk factor for congenital heart disease (CHD) in Chinese paediatric population was studied in view of the previously reported controversial results. METHODS: We searched literature including PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases that resulted in the identification of a total of 21 separate studies with 6414 subjects that met the inclusion criteria in the Chinese population. The quality assessment of the included studies was preformed and relevant information was collected. We chose the fixed-effect model or random-effect model to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI) where appropriate. Begg test was used to measure publication bias and sensitivity analyses were done to ensure authenticity of the outcome. RESULTS: We observed a significant association between MTHFR C677T polymorphism and CHD development in all the genetic models evaluated. The pooled ORs and 95% CIs in all genetic models indicated that children's MTHFR C677T polymorphism was significantly associated with CHD. CONCLUSION: Our study results indicate that MTHFR gene 677T polymorphism is a genetic risk factor in the development of CHD in Chinese paediatric population.
Assuntos
Povo Asiático/genética , Predisposição Genética para Doença , Cardiopatias Congênitas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Criança , China , Cardiopatias Congênitas/etnologia , HumanosRESUMO
BACKGROUND: Cs2K4Na [SiW9Nb3O40] (POM93) is a novel broad-spectrum antiviral agent with high activity, high stability, and low toxicity in vitro. Most toxicity studies for POM93 have been performed in cultured cell lines rather than in animals. Like other POMs, there is a lack of evidence for in vivo toxicity limits, oral bioavailability, and therapeutic applications. METHODS: The toxic properties of POM93 were evaluated comprehensively in vivo, including the acute and subchronic oral toxicity studies and genotoxicity tests. RESULTS: The acute toxicity study showed no abnormal changes or mortality in rats treated with POM93 even at the single high dose of 5000 mg/kg body weight. In the subchronic toxicity study, regardless of the body weight, the organ weight, and the hematological parameters, similar results were observed between the control group and the experimental groups. POM93 produced mild changes in rare hematological parameters in the liver and kidneys, but did not induce the clinical symptoms of liver or kidneys injury in rats as confirmed by histopathological analysis. Moreover, neither mutagenicity nor clastogenicity was caused by POM93 treatment in vitro and in vivo. CONCLUSIONS: The present study demonstrates that the oral administration of POM93 is presumed safe and poses a low risk of potential health risks.
Assuntos
Antivirais/toxicidade , Mutagênicos/toxicidade , Compostos de Tungstênio/toxicidade , Administração Oral , Animais , Antivirais/administração & dosagem , Feminino , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Mutagênicos/administração & dosagem , Estudos Prospectivos , Ratos , Ratos Wistar , Salmonella typhimurium/efeitos dos fármacos , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , Compostos de Tungstênio/administração & dosagemRESUMO
Activated tumor-associated fibroblasts (TAFs) with abundant fibroblast activation protein (FAP) expression attract tremendous attention in tumor progression studies. In this work, we report a rapid 24 h FAP activation method for fibroblasts using silicon nanowires (SiNWs) as culture substrates instead of growth factors or chemokines. In contrast with cells cultured on flat silicon which rarely express FAP, SiNW cultivated cells exhibit FAP levels similar to those found in cancerous tissue. We demonstrated that activated cells grown on SiNWs maintain their viability and proliferation in a time-dependent manner. Moreover, environmental scanning electron microscopy (ESEM) and focused ion beam and scanning electron microscopy (FIB-SEM) analysis clearly revealed that activated cells on SiNWs adapt to the structure of their substrates by filling inter-wire cavities via filopodia in contrast to cells cultured on flat silicon which spread freely. We further illustrated that the expression of FAP was rarely detected in activated cells after being re-cultured in Petri dishes, suggesting that the unique structure of SiNWs may have a certain influence on FAP activation.
Assuntos
Fibroblastos/metabolismo , Nanofios/química , Silício/química , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Endopeptidases , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Gelatinases/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Microscopia Eletrônica de Varredura , Nanofios/toxicidade , Serina Endopeptidases/metabolismoRESUMO
Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder. The patho-physiological characteristic of AD is abnormal deposition of fibrillar amyloid ß protein, intracellular neurofibrillary tangles, oxidative damage and neuronal death in the brain. Zinc is an important trace element in human body regulating many physiological processes. Increasing evidence suggests that the etiology of AD may involve disruptions of zinc homeostasis, and oxidative stress facilitating reactive oxygen species production is an early and sustained event in AD disease progression. Both Zn deficiency and Zn overload may affect cellular Zn distribution and be linked to neurodegeneration in AD. Meanwhile, Zn may play paradoxical roles in initiating and inhibiting oxidative stress and neurotoxicity. This review will focus on aspects of the role of zinc in AD, which includes a large body of research regarding zinc dyshomeostasis and its relation with oxidative stress.
Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Estresse Oxidativo , Zinco/metabolismo , Homeostase , HumanosRESUMO
Persistent organic pollutant exposure is strongly associated with the development of diabetes. The development of diabetes or alteration in blood glucose levels is associated with insulin resistance that precedes diabetes for many years. Omethoate is a commonly used insecticide in most developing countries. The present study was designed to elucidate the potent role of omethoate in developing insulin resistance in rats. Male Wistar rats were exposed to omethoate at the concentration of 1.5mg/kg body weight (1/40 LD50), 3 mg/kg body weight (1/20 LD50) and 6 mg/kg body weight (1/10 LD50) through gastric injection for 60 days; control group rats received PBS through gastric injection. The results showed that the levels of MDA, TNF-α and IL-6 were increased and the activities of SOD and GSH-Px were decreased in the right thigh muscles of rats exposed to omethoate. However, JNK, p38 MAPK and NF-κB in right thigh muscles of rats exposed to omethoate were activated. This study suggested that omethoate had a potential to cause insulin resistance.
Assuntos
Dimetoato/análogos & derivados , Inseticidas/toxicidade , Resistência à Insulina , Animais , Glicemia/análise , Dimetoato/toxicidade , Glutationa Peroxidase/metabolismo , Insulina/sangue , Interleucina-6/sangue , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Malondialdeído/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: To develop an HPLC method for simultaneous determination of gallic acid and hesperidin in Xiaogu capsule, in order to provide a simple, rapid and accurate method for quality control of the compound preparation of traditional Chinese medicine. METHOD: Xiaogu capsule was extracted with methanol heating reflux method. Synergi 4 mu Hydro-RP 80A (4.6 mm x 250 mm, 5 microm) was adopted as the chromatographic column, with acetonitrile--0.04 mol x L(-1) phosphate monobasic sodium solution (20: 80) as the mobile phase. The flow rate was 1.0 mL x min(-1), the detection wavelength was 283 nm, and the column temperature was 25 degrees C. RESULT: Under the conditions, gallic acid and hesperidin reached the baseline resolved peak, with a good linearity within the range of 21.6-216.0 mg x L(-1) (r = 0.999 93) for gallic acid, and 4.5-45.0 mg x L(-1) (r = 0.999 95) for hesperidin, respectively. Their average recoveries (n = 9) were 101.5% (RSD 3.7%) and 94.7% (RSD 2.7%), respectively. The average contents of gallic acid and hesperidin contained in Xiaogu capsule were detected to 5.10% and 0.091 1%, respectively. CONCLUSION: The method established in this study can determine the content of gallic acid and hesperidin contained in Xiaogu capsule in a rapid and accurate manner, which provided reference for quality evaluation of the medicine.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Ácido Gálico/análise , Hesperidina/análise , Cápsulas/análiseRESUMO
BACKGROUND: Gallic acid (GA) is a plant phenol isolated from water caltrop which is reported to have anti-inflammatory and anti-cancer effects. In this study, the antiproliferative effect of GA on human pancreatic cancer cell lines CFPAC-1 and MiaPaCa-2 as well as hepatocytes HL-7702 as normal cells was examined. Particularly, the mechanism of GA-induced apoptosis in MiaPaCa-2 cells in vitro was further studied. METHODS: Cell viability was measured using SRB assay, and apoptosis was detected by Hoechst staining and annexin V-PI staining assays. Mitochondrial membrane potential was detected by rhodamine-123 staining. Flow cytometry analysis was employed to detect the apoptosis-related events. RESULTS: GA inhibited the proliferation of CFPAC-1 and MiaPaCa-2 cells in a time- and dose-dependent manner, with IC(50)S of 102.3 ± 2.4 and 135.2 ± 0.6 µM at 48 h, respectively. GA treatment led to the increased proportion of cell apoptosis from 12.5 ± 0.72 to 78.3 ± 2.48% at the concentrations of 6.25 and 25.0 µg/ml, which was evidenced again by chromatins staining assay. Also, GA activated caspase-3, caspase-9, and reactive oxygen species, elevated Bax expression and [Ca(2+)](i) and reduced mitochondrial membrane potential (ΔΨm) in MiaPaCa-2 cells. Remarkably, when compared with human normal cells HL-7702 (IC(50) >100 µg/ml), GA showed selective toxicity for cancer cells. CONCLUSIONS: GA can function as a cancer-selective agent by inducing apoptosis in MiaPaCa-2 cells via the mitochondria-mediated pathways. To the best of our knowledge, GA should open up new opportunities for the therapy of pancreatic cancer.
Assuntos
Apoptose/efeitos dos fármacos , Ácido Gálico/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To extract the volatile components of water caltrop and kernel and to analyze them. METHOD: The volatiles were separated by supercritical fluid extraction (SFE) and determined by GC-MS. RESULT: The extraction rates of water caltrop and kernel were 5.96% and 0.23%, respectively. The components determined by normalization method were mainly 9, 12-octadecadienoic acid (Z, Z), but the content was different. CONCLUSION: The researches showed that the components in the volatile components of water caltrop and kernel were mainly 12-octadecadienoic acid (Z, Z), and then palmitinic acid, with a higher extraction rate of caltrop.
Assuntos
Ácido Linoleico/isolamento & purificação , Lythraceae/química , Óleos Voláteis/química , Ácido Palmítico/isolamento & purificação , Óleos de Plantas/química , Cromatografia com Fluido Supercrítico/métodos , Frutas/química , Cromatografia Gasosa-Espectrometria de Massas , Ácido Linoleico/análise , Óleos Voláteis/isolamento & purificação , Ácido Palmítico/análise , Óleos de Plantas/isolamento & purificação , Plantas Medicinais/química , Sementes/químicaRESUMO
Trihydroxybenzoic acid dimmer is an anti-tumor compound which is separated from water-caltrop. This study is aimed to investigate its anti-proliferation effect on HL-60 cells and the possible mechanism of inducing apoptosis. MTT assay was used to test HL-60 cells proliferation. The apoptosis, ROS levels and the mitochondrial membrane potential were detected by flow cytometry. Cytochrome c released from mitochondria to cytosol fraction was detected by Western blotting. The activity of Caspase-9 and Caspase-3 were measured by colorimetric method. It was found to inhibit HL-60 cells proliferation in a dose and time-dependent manner. Compared with control group, it caused the increase of ROS levels and a concomitant dissipation of the mitochondrial membrane potential and induced cytosolic accumulation of cytochrome c and activities Caspase-9 and Caspase-3. Therefore it can be concluded that mitochondrial-dependent pathways was involved in its induction of apoptosis of HL-60 cells.
Assuntos
Apoptose/efeitos dos fármacos , Citocromos c/metabolismo , Ácido Gálico/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Frutas/química , Ácido Gálico/isolamento & purificação , Células HL-60 , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Plantas Medicinais/químicaRESUMO
Pb and Al in blood and hair of child were determined by transverse heated graphite furnace atomic absorption spectrometry with NH4H2PO4 and Mg(NO3)2 as a modifier, which enhanced the temperature of ashing, eliminated the matrix interference and memorial effect. The method is rapid, simple and accurate. The characteristic mass of the method was 2.3 x 10(-11) g and 2.2 x 10(-11) g for Pb and Al respectively. The relative standard deviation of Pb and Al was 3.0% and 11.4%, respectively, and the recovery was 96%-102%.