Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 633
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Phys Chem Chem Phys ; 22(9): 5301-5313, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32096507

RESUMO

Biomedical industries are widely exploring the use of thermo-responsive polymers (TRPs) in the advanced development of drug delivery and in many other pharmaceutical applications. There is a great need to investigate the use of less toxic and more (bio-)compatible TRPs employing several additives, which could modify the conformational transition behavior of TRPs in aqueous solution. To move forward in this aspect, we have chosen the less toxic bio-based polymer poly(N-vinylcaprolactam) (PVCL) and three different methylamine-based osmolytes, trimethylamine N-oxide (TMAO), betaine and sarcosine, in order to investigate their particular interactions with the polymer segments in PVCL and therefore the corresponding changes in the thermo-responsive conformational behavior. Several biophysical techniques, UV-visible spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS) and laser Raman spectroscopy, as well as classical computer simulation methods such as molecular dynamics are employed in the current work. All the studied methylamines are found to favor the hydrophobic collapse of the polymer thus stabilizing the globular state of PVCL. Sarcosine is observed to cause the maximum decrease in lower critical solution temperature (LCST) of PVCL followed by TMAO and then betaine. The differences observed in the LCST values of PVCL in the presence of these molecules can be attributed to the different polymer-osmolyte interactions. The less sterically hindered N atom in the case of sarcosine causes a significant difference in the phase transition temperature values of PVCL compared to betaine and TMAO, where the nitrogen atom is buried by three methyl groups attached to it.


Assuntos
Caprolactama/análogos & derivados , Metilaminas/química , Simulação de Dinâmica Molecular , Polímeros/química , Betaína/química , Caprolactama/química , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Transição de Fase , Sarcosina/química , Temperatura de Transição , Água/química
2.
Chem Commun (Camb) ; 55(98): 14717-14720, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31702759

RESUMO

The final step in the biosynthesis of l-carnitine in humans is catalysed by the 2-oxoglutarate and ferrous iron dependent oxygenase, γ-butyrobetaine hydroxylase (BBOX). 1H and 19F NMR studies inform on the BBOX mechanism including by providing evidence for cooperativity between monomers in substrate/some inhibitor binding. The value of the 19F NMR methods is demonstrated by their use in the design of new BBOX inhibitors.


Assuntos
Inibidores Enzimáticos/química , Espectroscopia de Ressonância Magnética , gama-Butirobetaína Dioxigenase/metabolismo , Betaína/análogos & derivados , Betaína/síntese química , Betaína/química , Betaína/metabolismo , Carnitina/biossíntese , Carnitina/síntese química , Carnitina/química , Carnitina/metabolismo , Desenho de Drogas , Inibidores Enzimáticos/síntese química , Flúor/química , gama-Butirobetaína Dioxigenase/antagonistas & inibidores
3.
Ecotoxicol Environ Saf ; 184: 109580, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31493585

RESUMO

Ionic Liquids (ILs) are generically regarded as environmentally "harmless" and thus, assumed as "non-toxic". However, due to the endless design possibilities, their ecotoxicological profile is still poorly known. An accurate knowledge on the toxicity of a substance is required, under the scope of environmental regulation worldwide, before their application and commercialization. Knowledge on the relationship between the chemical structure and toxic effects is essential for the future design of more biocompatible solvents. Focusing on the use of ILs as base lubricants, lubricant additives, or even as potential working fluids for absorption heat pumps, the knowledge on its environmental impact is of great importance, due to the possibility of spills. In this specific context, four analogues of glycine-betaine-based ILs (AGB-ILs) and four glycine-betaine based ILs (GB-ILs) were synthesized and characterized. Their ecotoxicity was assessed using representatives of two trophic levels in aquatic ecosystems, the bacteria Allivibrio fischeri (commonly used as a screening test organism) and the microalgae Raphidocelis subcapitata (as an alternative test organism that has been proven very sensitive to several IL families). The microalgae were more sensitive than the bacteria, hence, following a precautionary principle, we recommend considering the toxicity towards microalgae as an indicator in future studies regarding the focused ILs. Although four of the studied ILs were derived from a natural amino acid, all were considered hazardous for the aquatic environment, disproving the primary theory that all ILs derived from natural compounds are benign. Furthermore, the modification in the structure of anion and the cation can lead to the increase of toxicity.


Assuntos
Betaína/química , Glicina/química , Líquidos Iônicos/toxicidade , Poluentes Químicos da Água/toxicidade , Aliivibrio fischeri/efeitos dos fármacos , Ânions/química , Cátions/química , Clorofíceas/efeitos dos fármacos , Ecotoxicologia , Biomarcadores Ambientais/efeitos dos fármacos , Líquidos Iônicos/síntese química , Líquidos Iônicos/química , Poluentes Químicos da Água/síntese química , Poluentes Químicos da Água/química
4.
J Chromatogr A ; 1608: 460419, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31439439

RESUMO

To increase metabolome coverage in global LC-MS metabolomics, often both reversed-phase liquid chromatography (RPLC) and hydrophilic-interaction liquid chromatography (HILIC) are implemented in parallel. However, there is a lack of consensus in the literature on the best HILIC stationary phase to employ for global metabolomics of human biological fluids. The objective of this study was to compare in detail the performance of two commonly employed HILIC phases: zwitterionic sulfobetaine ZIC-HILIC stationary phase and an underivatized silica HILIC stationary phase. During method development, the effect of salt concentration in the mobile phase was also investigated, and 5 mM ammonium acetate was selected. The stationary phases were evaluated using a mixture of 37 polar standards covering a range of logP values (-10 to 3.73), molecular weights (59-776 Da), charges (15 anions, 11 cations, and 11 neutral) as well as 17 lipid standards to understand phospholipid behaviour on the two stationary phases. The criteria used for the comparison included the quality of the chromatographic peak shape, adequate analyte retention, peak separation capability, and metabolite coverage. The zwitterionic ZIC-HILIC column provided better chromatographic performance over the silica stationary phase with 14 standards achieving good quality peaks compared to the 7 with the silica column. Only 2 standards were undetected with the ZIC-HILIC column compared to the 14 undetected with the silica column. In human plasma, 1966 and 1650 metabolites were observed on the ZIC-HILIC column in positive and negative electrospray ionization (ESI) respectively. On the silica HILIC column, 1773 and 2028 metabolites were observed in positive and negative ESI respectively, showing comparable performance of the two phases. Next, the effect of adding 10 mM ammonium phosphate to the samples to improve the analyte peak shape and metabolite coverage was investigated for both ZIC-HILIC and silica HILIC. In contrast with recently reported results for pZIC-HILIC, there was no clear evidence that ammonium phosphate addition was beneficial for human plasma samples. In conclusion, ZIC-HILIC provided better chromatographic performance for polar plasma metabolomics than underivatized silica in terms of chromatographic peak shape and chromatographic resolution, while maintaining comparable metabolite coverage. The addition of ammonium phosphate to human plasma was not beneficial for either of the two stationary phases.


Assuntos
Cromatografia Líquida/instrumentação , Plasma/química , Betaína/análogos & derivados , Betaína/química , Cromatografia Líquida/métodos , Cromatografia de Fase Reversa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Espectrometria de Massas/métodos , Metaboloma , Metabolômica/instrumentação , Metabolômica/métodos , Fosfatos/química , Dióxido de Silício/química
5.
J Agric Food Chem ; 67(32): 8958-8966, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31334644

RESUMO

The functional role of human milk oligosaccharides (HMOs) is closely associated with their type, composition, and structure. However, a detailed analysis of HMOs is difficult because neutral oligosaccharides (NHMOs) are mixed with sialylated oligosaccharides (SHMOs) in milk. Here, NHMOs were separated from SHMOs by DEAE-52 anion chromatography, and lactose was removed by graphite carbon solid-phase extraction. Lactose-free NHMOs were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) based on Girard's reagent P on-target derivatization (GPOD), and SHMOs were analyzed by MALDI-TOF-MS following selective sialic acid derivatization and GPOD. Sixty-four oligosaccharides were detected: 36 NHMOs, of which 28 were fucosylated, and 28 SHMOs, of which 8 with α-2,3-linked monosialic acid, 2 with α-2,3-linked disialic acid, 10 with α-2,6-linked monosialic acid, 2 with α-2,6-linked disialic acid, and 5 with both α-2,3- and α-2,6-linked disialic acid. These findings provide the groundwork for further characterization of the structure and activity of HMOs.


Assuntos
Betaína/análogos & derivados , Leite Humano/química , Oligossacarídeos/química , Betaína/química , Feminino , Humanos , Ácido N-Acetilneuramínico/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
6.
J Pharm Biomed Anal ; 175: 112761, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330280

RESUMO

A porous zwitterionic monolithic column was prepared to rapidly and efficiently separate lysozyme from egg white. The monolith was synthesized in a stainless steel HPLC column (5 cm × 4.6 mm i.d.) by in-situ thermal initiated co-polymerization of N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl) ammonium betaine (MSA) and ethylene dimethacrylate (EDMA). Due to the combination of quaternary ammonium and sulfonic groups on the monolithic matrix in one-pot process, the hydrophobic carbon chain and hydrophilic radical were obtained, which provided multiple driving forces for neutral, basic and acidic analytes, thus mix-mode chromatography mechanism contributed to the retention of different charged proteins. Properties such as composition, morphology and stability of the MSA-co-EDMA monolithic column were characterized by various analytical methods and the results showed that the monolith has large through-pores, good hydrophilicity and permeability. The effects of mobile phase pH and ionic strength on proteins were investigated, drawing the conclusion that the main adsorption and elution mechanism of lysozyme on MSA-co-EDMA monolith was electrostatic interaction, while those of other proteins included hydrophobic, hydrophilic and electrostatic interactions. Therefore, efficient separation of lysozyme and other proteins could be successfully achieved by switching the pH of mobile phase. Lysozyme can be adsorbed using 20 mmol/L phosphate buffer (pH 7.0) and eluted with 20 mmol/L phosphate buffer (pH 2.0). To prove the practicality of the monolithic column, it was also applied in the separation of lysozyme in egg white, which means the work has the potential for further development in proteome analysis of real biological samples.


Assuntos
Betaína/química , Clara de Ovo/química , Muramidase/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Metacrilatos/química , Nucleosídeos/química , Permeabilidade , Fenóis/química , Polimerização , Polímeros/química , Porosidade , Eletricidade Estática
7.
Bioprocess Biosyst Eng ; 42(11): 1721-1730, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31312897

RESUMO

Collecting microalgae from water with less energy and cost is significant to gain economic profit from microalgae harvesting and processing. Foam separation has certain advantages including low energy consumption, simple operation and easy maintenance of the equipment. Natural surfactants, compared to traditional surfactants, were used to harvest and separate the freshwater microalgae Desmodesmus brasiliensis by foam separation. Results showed a recovery percentage of 93.6% and an enrichment ratio of 23.1 with the natural surfactant cocamidopropyl betaine (CAPB), suggesting that this low-cost surfactant can be applied to microalgae biomass recovery on a commercial scale using foam separation with no negative effect on the content of microalgae chlorophyll, carotenoid or protein.


Assuntos
Betaína/análogos & derivados , Clorofíceas/citologia , Água Doce/microbiologia , Microalgas/citologia , Microalgas/isolamento & purificação , Tensoativos/química , Betaína/química , Floculação
8.
Int J Biol Macromol ; 137: 592-603, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31252019

RESUMO

In this work, we involved ultrasound-assisted click CuAAC in chitosan chemistry. Ultrasound-mediated CuAAC between propargylic ester of betaine and azido chitosan derivative proceeds fast in water under aerobic conditions and gives rise novel water-soluble triazole betaine chitosan derivatives. Using ionic gelation technique, we prepared and characterized nanoparticles from the synthesized chitosan derivatives. We studied antibacterial and transfection activity of the novel chitosan derivatives and their nanoparticles. The nanoparticles with size ca. 100 nm and ζ-potential ca. +65 mV proved to possess outstanding antibacterial activity, which is much more than that of the triazole betaine derivatives in their native form, and it is equal to the activity of ampicillin and gentamicin. Opposite, triazole betaine chitosan derivatives in their native form are characterized by remarkable transfection activity as compared with their nanoparticles. The most active triazole betaine chitosan derivatives are derivatives of moderate molecular weight with moderate degree of substitution. Their transfection activity is extremely high for chitosan species and it is comparable (values of the same order) with activity of Lipofectin - commercially available gene delivery vector.


Assuntos
Betaína/química , Quitosana/química , Cobre/química , Nanopartículas/química , Triazóis/química , Ondas Ultrassônicas , Alquinos/química , Antibacterianos/química , Antibacterianos/farmacologia , Azidas/química , Catálise , Quitosana/farmacologia , Química Click , Reação de Cicloadição , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Células HEK293 , Humanos , Peso Molecular , Transfecção
9.
Mar Drugs ; 17(6)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31207903

RESUMO

Various red algae have repeatedly been reported to produce a variety of UV-absorbing mycosporine-like amino acids (MAAs), compounds that are well-known as natural sun-screens, as well as a plethora of betaines, metabolites which contribute to the osmotic balance under salt stress. Among other Rhodophyta, Bostrychia scorpioides, which is thriving as epiphyte on salt marsh plants in Europe and hence experiences extreme environmental conditions such as desiccation, UV-stress and osmotic stress, has barely been investigated for its secondary metabolites. In the present study, seven mycosporine like-amino acids and two betaines were isolated from Bostrychia scorpioides using various chromatographic techniques. Their structures were confirmed by Nuclear Magnetic Resonance (NMR) spectroscopy and High Resolution Mass Spectrometry (HRMS). Six MAAs and one betaine were chemically characterized as new natural products.


Assuntos
Aminoácidos/química , Betaína/química , Produtos Biológicos/química , Rodófitas/química , Europa (Continente) , Espectroscopia de Ressonância Magnética/métodos , Raios Ultravioleta
10.
Nanoscale ; 11(21): 10167-10171, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31112182

RESUMO

We have introduced a non-hormonal hyperglycemia treatment strategy by using an injectable glucose-responsive boronic acid- zwitterionic nanogel. The synthesized system, similar to an artificial liver, is capable of storing/releasing glucose at high/low blood glucose concentrations. In vivo performance revealed that the injection of the nanogels can effectively regulate blood glucose in type 1 diabetic rats for at least 6 hours.


Assuntos
Betaína/análogos & derivados , Glicemia/metabolismo , Ácidos Borônicos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hiperglicemia , Nanoestruturas , Animais , Betaína/síntese química , Betaína/química , Betaína/farmacologia , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Géis , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Masculino , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Ratos , Ratos Sprague-Dawley
11.
Anal Biochem ; 575: 36-39, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30930198

RESUMO

Recombinase polymerase amplification (RPA) is a widespread isothermal amplification method and regarded as an excellent candidate to replace polymerase chain reaction. However, the specificity of RPA is not always satisfactory when the sample contains amounts of background DNA. Herein, we report a novel RPA method named betaine-assisted RPA (B-RPA) that uses inexpensive betaine to avoid nonspecific amplification effectively. Result show that nonspecific amplification is prone to occur in RPA if the primers have not been rigorously refined, especially in detecting samples with large amounts of background DNA. This problem has been addressed by adding betaine to the RPA reactions. Our data show that the addition of 0.8 M betaine can significantly increase specificity and efficiency simultaneously. This B-RPA method is also used to detect hepatitis B virus DNA in clinical plasma samples, thereby demonstrating the clinical practicability of B-RPA.


Assuntos
Betaína/química , Recombinases/química , Primers do DNA , Técnicas de Amplificação de Ácido Nucleico/métodos , Especificidade por Substrato
12.
Mater Sci Eng C Mater Biol Appl ; 100: 94-103, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948130

RESUMO

Various glucose-sensitive drug delivery platforms have been developed recently to treat diabetes. However, there is much less work has been reported on treatment of diabetes and vascular diabetes complications simultaneously. In this work, a novel polysaccharide-based micelle-hydrogel synergistic therapy system was fabricated to address this limitation. Zwitterionic dialdehyde starch-based micelles (SB-DAS-VPBA) were synthesized via single electron transfer-living radical polymerization (SET-LRP). Hydrophilic segment sulfobetaine (SB) and hydrophobic segment 4­vinylphenylboronic acid (VPBA) were grafted to the dialdehyde starch (DAS) backbones. Then, chitosan/dialdehyde starch derivatives (CS/SB-DAS-VPBA) micelle-hydrogel was synthesized by Schiff-base bonds. Insulin and nattokinase were loaded to obtain the micelle-hydrogel synergistic therapy system. In vitro drug delivery and blood clots dissolution behaviors were determined. Results suggest that the micelle-hydrogel synergistic therapy system not only possesses glucose-responsive insulin delivery property, but also provides good thrombolytic capacity. Thus, this micelle-hydrogel synergistic therapy system can be used as a platform for diabetes and vascular diabetes complications treatment.


Assuntos
Hidrogéis/química , Micelas , Amido/análogos & derivados , Betaína/análogos & derivados , Betaína/química , Ácidos Borônicos/química , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Hidrogéis/farmacologia , Amido/química , Compostos de Vinila/química
13.
Carbohydr Polym ; 213: 320-328, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879675

RESUMO

Utilization of chitosan as the host polymer of anion exchange membranes (AEMs) can avoid the carcinogenic chloromethylation step which is indispensable for aromatic polymers during their quaternization process. To further improve the ionic conductivity and mechanical stability, a hydroxide ion conductor (layered double hydroxides, LDHs) was intercalated by glycine betaine and then incorporated to quaternized chitosan and polyvinyl alcohol mixed matrix to prepare AEMs. Due to intercalated organic ions, the LDHs can be homogeneously dispersed in the matrix, thus promoting the load transfer from the matrix to stiff LDHs. The tensile strength and elongation of the composite membrane (5% intercalated LDHs content) are 23.6 MPa and 51.4% which are 71% and 44% respectively higher than those of the pure QCS/PVA membrane. Moreover, the hydroxide ion conductor (LDHs) and the intercalated quaternary ammonium groups could act as new OH- conductive sites and further enhance the ionic conductivity. The membrane with 5 wt.% intercalated LDHs loading shows ionic conductivity of ˜35.7 mS cm-1 (80 °C) and peak power density of 97.8 mW cm-2 which are respectively 42% and ˜50% higher than those of the pure membrane. Furthermore, better alkaline stability was also proved in the composite system, and the ionic conductivity of the composite membrane can retain 70% (only 49% for the pure membrane) even after immersing in a 1 M KOH for 168 h.


Assuntos
Betaína/química , Quitosana/química , Fontes de Energia Elétrica , Hidróxidos/química , Metanol/química , Álcool de Polivinil/química , Concentração de Íons de Hidrogênio
14.
ACS Appl Mater Interfaces ; 11(10): 9763-9776, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30776886

RESUMO

The combination of gene therapy and chemotherapy has recently received considerable attention for cancer treatment. However, low transfection efficiency and poor endosomal escape of genes from nanocarriers strongly limit the success of the clinical use of small interfering RNA (siRNA). In this study, a novel pH-responsive, surface-modified single-walled carbon nanotube (SWCNT) was designed for the codelivery of doxorubicin (DOX) and survivin siRNA. Polyethylenimine (PEI) was covalently conjugated with betaine, and the resulting PEI-betaine (PB) was further synthesized with the oxidized SWCNT to form SWCNT-PB (SPB), which exhibits an excellent pH-responsive lysosomal escape of siRNA. SPB was modified with the targeting and penetrating peptide BR2 (SPBB), thereby achieving considerably higher uptake of siRNA than SWCNT-PEI (SP) or SPB. Furthermore, SPBB-siRNA presented substantially lower survivin expression and higher apoptotic index than Lipofectamine 2000. DOX and survivin siRNA were adsorbed onto SPB to form DOX-SPBB-siRNA, and siRNA/DOX was released into the cytoplasm and nuclei of adenocarcinomic human alveolar basal epithelial (A549) cells without lysosomal retention. Compared with SPBB-siRNA or DOX-SPBB treatment alone, DOX-SPBB-siRNA significantly reduced tumor volume in A549 cell-bearing nude mice, demonstrating the synergistic effects of DOX and survivin siRNA. Pathological analysis also indicated the potential therapeutic effects of DOX-SPBB-siRNA on tumors without distinct damages to normal tissues. In conclusion, the novel functionalized SWCNT loaded with DOX and survivin siRNA was successfully synthesized, and the nanocomplex exhibited effective antitumor effects both in vitro and in vivo, thereby providing an alternative strategy for the codelivery of antitumor drugs and genes.


Assuntos
Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Survivina/genética , Células A549 , Animais , Betaína/química , Doxorrubicina/química , Resistencia a Medicamentos Antineoplásicos/genética , Terapia Genética/métodos , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Pulmonares/patologia , Lisossomos/química , Camundongos , Nanotubos de Carbono/química , Polietilenoimina/química , RNA Interferente Pequeno/farmacologia , Survivina/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
15.
AAPS PharmSciTech ; 20(3): 115, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771018

RESUMO

Naringenin exerts anti-inflammatory, hypolipidemic, and hepatoprotective effects; however, it shows low oral bioavailability because of poor water solubility. In this work, cocrystals of naringenin were formed to address these issues. Using the solution crystallization method, various naringenin cocrystals were prepared with different cocrystal coformers, including naringenin-nicotinamide, naringenin-isonicotinamide, naringenin-caffeine, naringenin-betaine, and naringenin-L-proline. The formation of these cocrystals was assayed by using DSC, XRD, and FT-IR spectroscopy. The stoichiometric ratio of naringenin and the CCFs in the corresponding cocrystals was investigated by NMR. The solubility of naringenin, as well as its dissolution rate, was markedly improved by forming cocrystals. The oral bioavailability of naringenin administered as naringenin-L-proline and naringenin-betaine cocrystals was achieved significantly greater than that of pure naringenin (p < 0.05). In particular, the Cmax of naringenin-L-proline and naringenin-betaine cocrystals were 2.00-fold and 3.35-fold higher, and the AUC of naringenin-L-proline and naringenin-betaine cocrystals were 2.39-fold and 4.91-fold, respectively, higher than pure naringenin in rats. With the naringenin-betaine cocrystals for oral delivery, the drug distribution in the liver was significantly increased compared to pure naringenin. Accordingly, the naringenin-betaine cocrystals showed improved anti-hyperlipidemia effects on the C57 BL/6J PNPLA3 I148M transgenic mouse hyperlipidemia model. Collectively, cocrystal formation is a promising way to increase the bioavailability of naringenin for treating hyperlipidemia.


Assuntos
Flavanonas/farmacologia , Flavanonas/farmacocinética , Hipolipemiantes/farmacologia , Hipolipemiantes/farmacocinética , Animais , Betaína/química , Disponibilidade Biológica , Cafeína/química , Varredura Diferencial de Calorimetria , Cristalização , Flavanonas/química , Hipolipemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Niacinamida/administração & dosagem , Prolina/química , Ratos , Ratos Sprague-Dawley , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier
16.
J Agric Food Chem ; 67(6): 1702-1710, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30661355

RESUMO

δ-Valerobetaine (δVB), a constitutive metabolite of ruminant milk, is produced in the rumen from free dietary Nε- trimethyllysine occurring ubiquitously in vegetable kingdom. The biological role of δVB is poorly known. Here, the antioxidant and anti-inflammatory potential of buffalo milk δVB was tested in vitro during high-glucose (HG)-induced endothelial damage. Results indicated that δVB (0.5 mM) ameliorated the HG cytotoxicity (0.57 ± 0.02 vs 0.41 ± 0.018 O.D. ( P < 0.01). Interestingly, buffalo milk extracts enriched with δVB showed improved significant efficacy in decreasing reactive oxygen species, lipid peroxidation, and cytokine release during HG treatment compared to milk extracts alone ( P < 0.05). It is noteworthy that δVB reduced the HG-activated inflammatory signal by modulating SIRT1 (0.96 ± 0.05 vs 0.85 ± 0.04 AU), SIRT6 (0.82 ± 0.04 vs 0.61 ± 0.03 AU), and NF-κB (0.85 ± 0.03 vs 1.23 ± 0.03 AU) ( P < 0.05). On the whole, our data show the first evidence of δVB efficacy in reducing endothelial oxidative stress and inflammation, suggesting a potential role of this betaine as a novel dietary compound with health-promoting properties.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Betaína/farmacologia , Leite/química , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Betaína/química , Búfalos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo
17.
Anal Chim Acta ; 1048: 105-114, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30598139

RESUMO

Sensitive glycomics analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is of great importance but significantly hampered by their low ionization efficiency and labile sialic acid moieties. Chemical derivatization offers a viable way to improve both the ionization efficiency and analytical sensitivity of the glycans in MS analysis by altering their hydrophobicity or charge property. Here we employed Girard's reagent T (GT) for on-target derivatization (GTOD) of reducing glycan under mild acid condition to form stable hydrazones at room temperature, allowing rapid and sensitive identification of neutral and sialylated glycans in positive-ion mode as only permanently positive charged molecular ions without multiple ion adducts by MALDI-TOF-MS. The MS signal intensities of lactose, sialylated N-glycans derived from bovine fetuin and neutral N-glycans derived from RNaseB and ovalbumin were boosted by 7.44, 9.13, 12.96 and 13.47 folds on average (n = 3), respectively. More importantly, after GTOD strategy, unwanted desialylation of sialylated glycans during MS was suppressed. The detection limit of the assay is desirable since the nanogram of N-glycans derived from 0.16 µg ovalbumin could be detected. The assay demonstrated good stability (RSD≤2.95%, within 10 days), reliable reproducibility (RSD = 2.96%, n = 7) and a desirable linear dynamic range from 78 nmol/mL to 10 µmol/mL. The strategy has been successfully applied to MS analysis of reducing glycans from human milks, neutral and sialylated O-, N-glycans from glycoproteins, and reducing glycans derived from glycosphingolipids, presenting neater [M]+ signals which allow detection of more low-abundance glycans and assignation of Neu5Ac vs. Neu5Gc or fucose vs. hexose in glycans due to the absence of the ambiguous interpretation from multiple peaks (ion adducts [M+Na]+ and [M+K]+). Moreover, the GTOD assay prevents desialylation during MALDI-TOF-MS profiling and enables distinct linkage-specific characterization of terminal sialic acids of N-glycans derived from human serum protein when combines with an esterification.


Assuntos
Betaína/análogos & derivados , Glicômica/métodos , Oligossacarídeos/química , Polissacarídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Betaína/química , Proteínas Sanguíneas/química , Feminino , Glicoproteínas/química , Glicoesfingolipídeos/química , Humanos , Proteínas do Leite/química , Leite Humano/química , Reprodutibilidade dos Testes , Ácidos Siálicos/química
18.
Langmuir ; 35(5): 1727-1739, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29925240

RESUMO

Poly(ethylene terephtalate) (PET)-based materials face general biofouling issues that we addressed by grafting a copolymer of glycidyl methacrylate and sulfobetaine methacrylate, poly(GMA- r-SBMA). The grafting procedure involved a dip-coating step followed by UV-exposure and led to successful grafting of the copolymer as evidenced by X-ray photoelectron spectroscopy and zeta potential measurements. It did not modify the pore size nor the porosity of the PET membranes. In addition, their surface hydrophilicity was considerably improved, with a water contact angle falling to 30° in less than 20 s and 0° in less than 1 min. The effect of copolymer concentration in the coating bath (dip-coating procedure) and UV exposure time (UV step) were scrutinized during biofouling studies involving several bacteria such as Escherichia coli and Stenotrophomonas maltophilia, but also whole blood and HT1080 fibroblasts cells. The results indicate that if all conditions led to improved biofouling mitigation, due to the efficiency of the zwitterionic copolymer and grafting procedure, a higher concentration (15 mg/mL) and longer UV exposure time (at least 10 min) enhanced the grafting density which reflected on the biofouling results and permitted a better general biofouling control regardless of the nature of the biofoulant (bacteria, blood cells, fibroblasts).


Assuntos
Polietilenotereftalatos/química , Aderência Bacteriana/efeitos dos fármacos , Betaína/análogos & derivados , Betaína/síntese química , Betaína/química , Incrustação Biológica/prevenção & controle , Células Sanguíneas/efeitos dos fármacos , Linhagem Celular Tumoral , Compostos de Epóxi/síntese química , Compostos de Epóxi/química , Escherichia coli/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Metacrilatos/síntese química , Metacrilatos/química , Polietilenotereftalatos/síntese química , Stenotrophomonas maltophilia/efeitos dos fármacos
19.
Langmuir ; 35(5): 1391-1403, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30134095

RESUMO

A procedure for the preparation of copolymers bearing sulfobetaine and carboxybetaine methacrylic-based monomers by free-radical polymerization is described and discussed. A combination of monomers affects the upper critical solution temperature (UCST) in water and in the presence of a simple NaCl electrolyte while retaining the zwitterionic character. In addition, hydrogel samples were prepared and showed tunable water structure and mechanical properties. The total nonfreezable water content decreases with the amount of carboxybetaine segment in the hydrogel feed and the compression moduli were in a range of 0.7-1.6 MPa. Responses to external conditions such as temperature and ion strength were investigated and a potential application such as modulated thermal detection is proposed. The presence of the carboxylate group in the carboxybetaine segment enables a small fluorescence probe and peptide bearing RDG motif to be attached to polymer and hydrogel samples, respectively. The hydrogel samples functionalized with the RGD motif exhibit controlled cell adhesion. Such synthetic strategy based on combination of different zwitterionic segments offers a simple pathway for the development of zwitterionic materials with programmable properties.


Assuntos
Adesão Celular/efeitos dos fármacos , Ácidos Polimetacrílicos/farmacologia , Água/química , Células 3T3 , Animais , Betaína/análogos & derivados , Betaína/química , Hidrogéis/síntese química , Hidrogéis/química , Hidrogéis/farmacologia , Concentração de Íons de Hidrogênio , Camundongos , Concentração Osmolar , Polimerização , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Temperatura de Transição , Substâncias Viscoelásticas/síntese química , Substâncias Viscoelásticas/química , Substâncias Viscoelásticas/farmacologia
20.
Langmuir ; 35(5): 1642-1651, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30114915

RESUMO

Biomaterials-associated infections (BAIs) are related to bacterial colonization on medical devices, which lead to a serious medical burden, such as increased healthcare cost, prolonged hospital stays, and high mortality and morbidity. To reduce the risk of infections, in this work, a new approach which makes use of a bioinspired coating with dual antimicrobial and antifouling functions was developed through rapid deposition of functional polydopamine (pDA) and antimicrobial copper ions, and subsequent conjugation of zwitterionic antifouling sulfobetaine (SB) moieties by the aza-Michael addition reaction. pDA permits surface-independent versatile functionalization on a variety of substrates, such as TiO2, SiO2, gold, plastics, and Nitinol alloy. The characterizations for chemical elemental compositions and hydrophilicity by X-ray photoelectron spectroscopy and contact angle goniometer, respectively, indicating the successful grafting of SB moieties and the presence of copper ions in the pDA adlayers. Ellipsometric thicknesses of the thin films were followed to monitor the formation of pDA films and the changes after the post conjugation. UV-vis spectroscopy and inductively coupled plasma-mass spectrometry revealed the coordination structure of catechol-Cu, and release profile of Cu2+ from the constructed functional coatings. The superhydrophilic and charge-balanced SB interface allowed effective resistance of bacterial adsorption. Intriguingly, we scrutinized that the release of bactericidal copper ions enables killing the residual amount of adsorbed bacteria. Moreover, viability tests for fibroblast cells indicate the excellent biocompatibility of the developed medical coatings. For real-world implementation, the antifouling and antimicrobial coatings were applied on commercially available silicone-based urinary catheters, and the existence of bacteria was evaluated by using the plate-counting assay. The results showed an undetectable level of living bacteria. Consequently, the dual functional medical coating offers a promising approach to eliminate BAIs for practical applications.


Assuntos
Antibacterianos/farmacologia , Incrustação Biológica/prevenção & controle , Materiais Revestidos Biocompatíveis/farmacologia , Animais , Antibacterianos/química , Aderência Bacteriana/efeitos dos fármacos , Betaína/análogos & derivados , Betaína/química , Betaína/farmacologia , Materiais Revestidos Biocompatíveis/química , Cobre/química , Cobre/farmacologia , Escherichia coli/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Camundongos , Células NIH 3T3 , Polímeros/química , Polímeros/farmacologia , Staphylococcus epidermidis/efeitos dos fármacos , Cateteres Urinários/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA