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1.
Molecules ; 26(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443601

RESUMO

Surfactant aggregates have long been considered as a tool to improve drug delivery and have been widely used in medical products. The pH-responsive aggregation behavior in anionic gemini surfactant 1,3-bis(N-dodecyl-N-propanesulfonate sodium)-propane (C12C3C12(SO3)2) and its mixture with a cationic monomeric surfactant cetyltrimethylammonium bromide (CTAB) have been investigated. The spherical-to-wormlike micelle transition was successfully realized in C12C3C12(SO3)2 through decreasing the pH, while the rheological properties were perfectly enhanced for the formation of wormlike micelles. Especially at 140 mM and pH 6.7, the mixture showed high viscoelasticity, and the maximum of the zero-shear viscosity reached 1530 Pa·s. Acting as a sulfobetaine zwitterionic gemini surfactant, the electrostatic attraction, the hydrogen bond and the short spacer of C12C3C12(SO3)2 molecules were all responsible for the significant micellar growth. Upon adding CTAB, the similar transition could also be realized at a low pH, and the further transformation to branched micelles occurred by adjusting the total concentration. Although the mixtures did not approach the viscosity maximum appearing in the C12C3C12(SO3)2 solution, CTAB addition is more favorable for viscosity enhancement in the wormlike-micelle region. The weakened charges of the headgroups in a catanionic mixed system minimizes the micellar spontaneous curvature and enhances the intermolecular hydrogen-bonding interaction between C12C3C12(SO3)2, facilitating the formation of a viscous solution, which would greatly induce entanglement and even the fusion of wormlike micelles, thus resulting in branched microstructures and a decline of viscosity.


Assuntos
Reologia , Tensoativos/química , Cetrimônio/química , Glutamatos/química , Concentração de Íons de Hidrogênio , Micelas , Viscosidade
2.
Methods Mol Biol ; 2358: 83-91, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270047

RESUMO

Protein phosphorylation is one of the most important posttranslational modifications. The phosphorylation and dephosphorylation of proteins regulate almost every cellular process, and the understanding of their functions can provide insights into the regulation of living systems at the molecular level. In recent years, both the rapid developments of enrichment approaches for phosphoproteins and MS techniques have improved the research scope and depth of phosphoproteomics. Using NaCl-treated soybean roots as the experimental materials, this chapter introduces the protein extraction, digestion with filter-aided sample preparation (FASP), eight-plex iTRAQ labeling, TiO2-based enrichment of phosphopeptides, LC-MS/MS analysis, as well as bioinformatic methods and protocols.

4.
Sci Rep ; 7(1): 15431, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29133875

RESUMO

Ginseng, a popular herbal remedy, is often used in combination with other drugs to achieve the maximum therapeutic response. Shenfu (SFI) and Shenmai injection (SMI) have been widely used to treat cardiovascular disease in China. Our study explored the cardiovascular protection of SFI and SMI in eNOS knockout mice to investigate the differences and similarities of the two ginseng-combinations. Transthoracic echocardiography was performed to evaluate the left ventricular structure and function at baseline and 3, 7, and 14 days after drug administration. Agilent Gene Expression microarrays were used to demonstrate the gene expression profiling of the thoracic aorta. Ingenuity Pathway Analysis was performed to evaluate the mechanism improved by SFI and SMI in eNOS knockout mice. Both SFI and SMI could modulate Gadd45 Signaling from TOP15 canonical pathways. Moreover, SFI showed a better effect in the early treatment stage and improved myocardial function via GATA4, GATA6 and COL3A1. Meanwhile, SMI exerted better protective effects at the chronic stage, which may be related to endothelium protection by VEGFA and ACE. The advantage of multi-target by drug combination in progression of complex diseases should be noticed. The appropriate adjustment of drug combination could lead to a better accurate medical care in clinic.


Assuntos
Aorta Torácica/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Coração/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/genética , Animais , Aorta Torácica/metabolismo , Doenças Cardiovasculares/genética , Modelos Animais de Doenças , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Ecocardiografia , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Perfilação da Expressão Gênica , Coração/diagnóstico por imagem , Coração/fisiologia , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Knockout , Miocárdio/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Panax/química , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
5.
PLoS One ; 12(4): e0176777, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28453571

RESUMO

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.


Assuntos
Tolerância a Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Nitroglicerina/farmacologia , Vasodilatadores/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , GMP Cíclico/metabolismo , Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , Combinação de Medicamentos , Ecocardiografia , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Masculino , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Técnicas de Cultura de Tecidos
6.
Front Microbiol ; 8: 248, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28270802

RESUMO

The incidence and prevalence of intestinal parasites in children is most likely due to lack of natural or acquired resistance and differences in behavior and habits closely related to environmental and socioeconomic determinants. The most important protozoa that parasitize humans are Giardia, Entamoeba, Blastocystis, and Cryptosporidium. These parasites present wide intraspecific genetic diversity and subsequently classified into assemblages and subtypes. The Amazon basin is the largest in the world and is the fifth freshwater reserve on the planet. Contradictorily, people living in these areas (Indigenous populations) have poor quality of life, which favors the infection of diseases of fecal-oral transmission. The aim of this work was to unravel the molecular epidemiology of Giardia, Blastocystis and Cryptosporidium across four communities (Puerto Nariño, San Juan del Soco, Villa Andrea and Nuevo Paraíso). We obtained 284 fecal samples from children under 15 years old that were analyzed by direct microscopy (261 samples) and Real Time PCR (qPCR) (284 samples). The positive samples for these protozoa were further characterized by several molecular markers to depict assemblages and subtypes. We observed a frequency of Giardia infection by microscopy of 23.7% (62 samples) and by qPCR of 64.8% (184 samples); for Blastocystis by microscopy of 35.2% (92 samples) and by qPCR of 88.7% (252 samples) and for Cryptosporidium only 1.9% (5 samples) were positive by microscopy and qPCR 1.8% (5 samples). Regarding the Giardia assemblages, using the glutamate dehydrogenase (gdh) marker we observed AI, BIII and BIV assemblages and when using triose phosphate isomerase (tpi) we observed assemblages AI, AII, BIII and BIV. In contrast, Blastocystis STs detected were 1, 2, 3, 4, and 6. Lastly, the species C. viatorum, C. hominis (with the subtypes IdA19 and IaA12R8) and C. parvum (with the subtype IIcA5G3c) were identified. We observed a high profile of zoonotic transmission regarding the Giardia assemblages and Blastocystis STs/alleles. Also, we highlight the elevated frequency of infection by these two protozoans suggesting an active transmission in the area. Our findings reinforces the need to deploy better epidemiological surveillance systems for enteric pathogens in the area.

7.
J Matern Fetal Neonatal Med ; 29(24): 4065-9, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26902393

RESUMO

OBJECTIVES: Small-for-gestational-age (SGA) results from abnormalities of the feto-placental-maternal unit. Cytokine profiles during early pregnancy may predict placental changes that lead to SGA, however it is unknown if these altered profiles precede conception. We examined the role of maternal cytokines prior to conception as risk factors for subsequent delivery of an SGA infant. METHODS: We included a sample of 80 women and their offspring from a large trial of pre-conceptual multiple micronutrient supplementation. Plasma samples collected before conception were tested with a high sensitivity multiplex assay for IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IFNγ, and TNFα. RESULTS: Pre-conceptual IL-13 and IFNγ were lower in women who gave birth to an SGA child than among control women (0.81 versus 1.14 pg/ml and 7.81 versus 11.01 pg/ml, respectively). Multivariable logistic regression showed that IL-13 (p = 0.029) and IFNγ (p = 0.015) were both inversely associated with SGA. CONCLUSIONS: These results suggest maternal immune function prior to conception may indicate an unfavorable immune balance leading to placental abnormalities and high risk of SGA. Preconception assessment of cytokine profiles could potentially contribute to early detection of SGA and to the timely implementation of interventions to prevent it.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Interferon gama/sangue , Interleucinas/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido Pequeno para a Idade Gestacional/imunologia , Projetos Piloto , Cuidado Pré-Concepcional , Distribuição Aleatória , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Risco , Estatísticas não Paramétricas , Adulto Jovem
8.
PLoS One ; 8(11): e78652, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24265704

RESUMO

UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.


Assuntos
Antígenos Nucleares/genética , Dano ao DNA , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica/genética , Oxirredutases N-Desmetilantes/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Sequência de Bases , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Proteínas de Drosophila/genética , Drosophila melanogaster/citologia , Drosophila melanogaster/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Histonas/metabolismo , Autoantígeno Ku , Metilação/efeitos da radiação , Oxirredutases N-Desmetilantes/genética , Regiões Promotoras Genéticas/genética , Regiões Promotoras Genéticas/efeitos da radiação , Regulação para Cima/genética , Regulação para Cima/efeitos da radiação
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