RESUMO
The most common type of endocrine disease is type 2 diabetes mellitus (T2DM); genetic factors contribute to the development to T2DM. In this study, we investigated the role of the Leu53Leu, Arg213Gly, and Ala40Thr polymorphisms in extracellular superoxide dismutase (EC-SOD) gene in the development of T2DM in a Chinese population. DNA was extracted from peripheral blood samples obtained from 256 T2DM patients and 324 control subjects recruited from our hospital between January 2013 and March 2015. DNA was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The obtained data was then statistically analyzed. The chi-square test revealed a statistically significant difference in the genotype frequencies of EC-SOD Ala40Thr (χ2 = 13.26, P = 0.001) between the patients and controls. Unconditional regression analysis indicated that the GA and AA genotypes of EC-SOD Ala40Thr were associated with an increased risk of T2DM compared to the GG genotype {adjusted odds ratio (OR) [95% confidence interval (CI)] = 1.46 (1.01-2.11) and 2.67 (1.48-4.85), respectively}. In the dominant model, the GA+AA genotype of EC-SOD Ala40Thr was correlated with a higher risk of T2DM, in comparison with the GG genotype (OR = 1.64, 95%CI = 1.16-2.33). In the recessive model, AA of EC-SOD Ala40Thr showed a 2.19-fold higher risk of developing T2DM than the GG+GA genotype. In conclusion, people with the Ala40Thr polymorphism in EC-SOD are at a higher risk of developing T2DM; therefore, this may be utilized as a biomarker for early screening of T2DM in a Chinese population.
Assuntos
Povo Asiático/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Superóxido Dismutase/genética , Adulto , Alanina/genética , Arginina/genética , Feminino , Predisposição Genética para Doença , Genótipo , Glutamina/genética , Humanos , Leucina/genética , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Treonina/genéticaRESUMO
High plasma levels of homocysteine (Hcy) promote the progression of neurodegenerative diseases. However, the mechanism by which Hcy mediates neurotoxicity has not been elucidated. We observed that upon incubation with Hcy, the viability of a neuroblastoma cell line Neuro2a declined in a dose-dependent manner, and apoptosis was induced within 48 h. The median effective concentration (EC50) of Hcy was approximately 5 mM. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nuclear translocation and acylation has been implicated in the regulation of apoptosis. We found that nuclear translocation and acetylation of GAPDH increased in the presence of 5 mM Hcy and that higher levels of acetyltransferase p300/CBP were detected in Neuro2a cells. These findings implicate the involvement of GAPDH in the mechanism whereby Hcy induces apoptosis in neurons. This study highlights a potentially important pathway in neurodegenerative disorders, and a novel target pathway for neuroprotective therapy.
Assuntos
Apoptose/efeitos dos fármacos , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Homocisteína/farmacologia , Fármacos Neuroprotetores/farmacologia , Acetilação , Acetiltransferases/análise , Animais , Apoptose/fisiologia , Western Blotting , Contagem de Células , Extratos Celulares/química , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Sobrevivência Celular/fisiologia , Indução Enzimática , Imunofluorescência , Homocisteína/administração & dosagem , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Fatores de Tempo , Fatores de Transcrição de p300-CBP/metabolismoRESUMO
High plasma levels of homocysteine (Hcy) promote the progression of neurodegenerative diseases. However, the mechanism by which Hcy mediates neurotoxicity has not been elucidated. We observed that upon incubation with Hcy, the viability of a neuroblastoma cell line Neuro2a declined in a dose-dependent manner, and apoptosis was induced within 48 h. The median effective concentration (EC50) of Hcy was approximately 5 mM. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nuclear translocation and acylation has been implicated in the regulation of apoptosis. We found that nuclear translocation and acetylation of GAPDH increased in the presence of 5 mM Hcy and that higher levels of acetyltransferase p300/CBP were detected in Neuro2a cells. These findings implicate the involvement of GAPDH in the mechanism whereby Hcy induces apoptosis in neurons. This study highlights a potentially important pathway in neurodegenerative disorders, and a novel target pathway for neuroprotective therapy.
Assuntos
Animais , Coelhos , Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Homocisteína/farmacologia , Acetilação , Acetiltransferases/análise , Fatores de Tempo , Contagem de Células , Extratos Celulares/química , Núcleo Celular/metabolismo , Sobrevivência Celular/fisiologia , Indução Enzimática , Western Blotting , Imunofluorescência , Apoptose/fisiologia , Fármacos Neuroprotetores/administração & dosagem , Linhagem Celular Tumoral , Fatores de Transcrição de p300-CBP/metabolismo , Homocisteína/administração & dosagemRESUMO
The objective of this study was to determine the ability of bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) to repair large segmental radial bone defects in rabbits. We treated calf cancellous bones with 3 mg/L BMP (Group A), 5 µg/L FGF (Group B), or 3 mg/L BMP plus 5 µg/L FGF (Group C). A bone damage model was established using healthy radii from rabbits. The complexes were implanted in the areas of the bone defects in the radii. After successful transplantation, the rabbits underwent radiographic imaging, and bone graft specimens were detected by histopathology methods. Biomechanical indexes were also assessed in order to observe the healing status of the bone defects. Our results indicated that the repair of bone defects was significantly better in Group C compared to the other 2 groups. Therefore, we concluded that combining BMP and FGF significantly promoted bone defect repair and achieved effects that were superior to the use of BMP alone.
Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Transplante Ósseo , Fatores de Crescimento de Fibroblastos/administração & dosagem , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Regeneração Óssea/genética , Bovinos , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/crescimento & desenvolvimento , Xenoenxertos/diagnóstico por imagem , Xenoenxertos/efeitos dos fármacos , Coelhos , Radiografia , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVE: To determine whether neurally adjusted ventilatory assist (NAVA), a new method of mechanical ventilation that delivers pressure assistance that is proportional to the electrical activity of the diaphragm (EAdi), could lower the inspiratory pressure and respiratory muscle load in preterm infants supported with ventilators. STUDY DESIGN: Twenty-six mechanically ventilated preterm infants were randomized to crossover ventilation with NAVA and synchronized intermittent mandatory ventilation (SIMV) with pressure support (PS) for 4 hours each in a randomized order. A 1-hour interval for washout was provided between the 2 modes of ventilation. The ventilator settings were adjusted to maintain similar levels of end-tidal partial pressure of CO(2). The ventilator parameters, vital signs, and gas exchange effects under the 2 ventilatory modes were compared. RESULTS: Nineteen infants completed the 9-hour crossover comparison protocol. Peak inspiratory pressure (PIP), work of breathing, and peak EAdi with NAVA were lower than those in SIMV with PS. Calculated tidal volume to peak EAdi ratio and PIP to peak EAdi ratio were higher with NAVA. There were no significant differences in mean airway pressure, inspiratory oxygen fraction, and blood gas values. The measurements of vital signs did not differ significantly between the 2 modes. CONCLUSION: NAVA lowered PIP and reduced respiratory muscle load in preterm infants at equivalent inspiratory oxygen fraction and partial pressure of CO(2) of capillary blood in comparison with SIMV with PS.
Assuntos
Respiração Artificial/métodos , Estudos Cross-Over , Diafragma/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/terapia , Suporte Ventilatório Interativo , Ventilação com Pressão Positiva Intermitente/métodos , Masculino , Oxigênio/química , Projetos Piloto , Pressão , Estudos Prospectivos , Respiração , Transtornos Respiratórios/terapia , Volume de Ventilação Pulmonar , Ventiladores MecânicosRESUMO
Phenylpropanoids, including flavonoids and stilbenes, are plant secondary metabolites with potential pharmacological and nutraceutical properties. To expand the applicability of Streptomyces venezuelae as a heterologous host to plant polyketide production, flavonoid and stilbene biosynthetic genes were expressed in an engineered strain of S. venezuelae DHS2001 bearing a deletion of native pikromycin polyketide synthase gene. A plasmid expressing the 4-coumarate/cinnamate:coenzyme A ligase from Streptomyces coelicolor (ScCCL) and the chalcone synthase from Arabidopsis thaliana (atCHS) under the control of a single ermE* promoter was constructed and introduced into S. venezuelae DHS2001. The resulting strain produced racemic naringenin and pinocembrin from 4-coumaric acid and cinnamic acid, respectively. Placement of an additional ermE* promoter upstream of the codon-optimized atCHS (atCHS(op)) gene significantly increased the yield of both flavanones. Expression of codon-optimized chalcone isomerase gene from Medicago sativa, together with ScCCL and atCHS(op) genes led to production of (2S)-flavanones, but the yield was reduced. On the other hand, a recombinant strain harboring the ScCCL and codon-optimized stilbene synthase gene from Arachis hypogaea generated stilbenes such as resveratrol and pinosylvin. This is the first report on the heterologous expression of plant phenylpropanoid biosynthetic pathways in Streptomyces genus.