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1.
Molecules ; 28(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36985769

RESUMO

Herein, we describe a one-step method for synthesizing cationic acrylate-based core-shell latex (CACS latex), which is used to prepare architectural coatings with excellent antimicrobial properties. Firstly, a polymerizable water-soluble quaternary ammonium salt (QAS-BN) was synthesized using 2-(Dimethylamine) ethyl methacrylate (DMAEMA) and benzyl bromide by the Hoffman alkylation reaction. Then QAS-BN, butyl acrylate (BA), methyl methacrylate (MMA), and vinyltriethoxysilane (VTES) as reactants and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AIBA) as a water-soluble initiator were used to synthesize the CACS latex. The effect of the QAS-BN dosage on the properties of the emulsion and latex film was systematically investigated. The TGA results showed that using QAS-BN reduced the latex film's initial degradation temperature but improved its thermal stability. In the transmission electron microscopy (TEM) photographs, the self-stratification of latex particles with a high dosage of QAS-BN was observed, forming a core-shell structure of latex particles. The DSC, TGA, XPS, SEM, and performance tests confirmed the core-shell structure of the latex particles. The relationship between the formation of the core-shell structure and the content of QAS-BN was proved. The formation of the core-shell structure was due to the preferential reaction of water-soluble monomers in the aqueous phase, which led to the aggregation of hydrophilic groups, resulting in the formation of soft-core and hard-shell latex particles. However, the water resistance of the films formed by CACS latex was greatly reduced. We introduced a p-chloromethyl styrene and n-hexane diamine (p-CMS/EDA) crosslinking system, effectively improving the water resistance in this study. Finally, the antimicrobial coating was prepared with a CACS emulsion of 7 wt.% QAS-BN and 2 wt.% p-CMS/EDA. The antibacterial activity rates of this antimicrobial coating against E. coli and S. aureus were 99.99%. The antiviral activity rates against H3N2, HCoV-229E, and EV71 were 99.4%, 99.2%, and 97.9%, respectively. This study provides a novel idea for the morphological design of latex particles. A new architectural coating with broad-spectrum antimicrobial properties was obtained, which has important public health and safety applications.


Assuntos
Anti-Infecciosos , Escherichia coli , Emulsões/química , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Metacrilatos/farmacologia , Água/química
2.
ACS Appl Mater Interfaces ; 14(40): 45178-45188, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36178205

RESUMO

Noninvasive photothermal therapy (PTT) is an emerging strategy for eliminating multidrug-resistant (MDR) bacteria that achieve sterilization by generating temperatures above 50 °C; however, such a high temperature also causes collateral damage to healthy tissues. In this study, we developed a low-temperature PTT based on borneol-containing polymer-modified MXene nanosheets (BPM) with bacteria-targeting capabilities. BPM was fabricated through the electrostatic coassembly of negatively charged two-dimensional MXene nanosheets (2DM) and positively charged quaternized α-(+)-borneol-poly(N,N-dimethyl ethyl methacrylate) (BPQ) polymers. Integrating BPQ with 2DM improved the stability of 2DM in physiological environments and enabled the bacterial membrane to be targeted due to the presence of a borneol group and the partially positive charge of BPQ. With the aid of near-infrared irradiation, BPM was able to effectively eliminate methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) through targeted photothermal hyperthermia. More importantly, BPM effectively eradicated more than 99.999% (>5 orders of magnitude) of MRSA by localized heating at a temperature that is safe for the human body (≤40 °C). Together, these findings suggest that BPM has good biocompatibility and that membrane-targeting low-temperature PTT could have great therapeutic potential against MDR infections.


Assuntos
Hipertermia Induzida , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Canfanos , Escherichia coli , Humanos , Hipertermia Induzida/métodos , Metacrilatos/farmacologia , Terapia Fototérmica , Polímeros/farmacologia , Temperatura
3.
Int J Biol Macromol ; 218: 488-505, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35878666

RESUMO

A new kind of Camellia sinensis-loaded nanocomposite hydrogel based on modified gelatin/iron-metal-organic framework was developed as an antibacterial wound dressing. Gelatin as a biocompatible natural polymer was modified with methacrylate anhydride to produce gelatin methacrylate. Thereafter, acrylic acid and acrylamide were grafted on gelatin methacrylate during an aqueous polymerization process. To enhance the porosity, mechanical strength, and drug loading capability of the hydrogel and reduce its toxicity, iron- based metal-organic framework was incorporated within the hydrogel. To add more functionality to the final wound dressing, Camellia sinensis, an antibacterial herbal drug was loaded on the hydrogel. The structural and chemical properties of prepared nanocomposite hydrogel were investigated by FTIR, XRD, SEM, and TGA techniques. The incorporation of iron-based metal-organic framework within the hydrogel matrix led to an increase in its water absorption value from 400.10 to 547.96 (g/g). The release study of Camellia sinensis (CS) extract from the prepared nanocomposite hydrogel exhibited a sustained release manner. The antibacterial test revealed the nanocomposite hydrogel contain extract has an effective antibacterial function against "Bacillus serous", "Staphylococcus aureus", "Streptococcus mutans"," Escherichia coli", "Klebsiella pneumoniae", and "Pseudomonas aeruginosa" bacteria. Therefore, the synthesized nanocomposite is a good candidate as an antibacterial hydrogel wound dressing. .


Assuntos
Camellia sinensis , Estruturas Metalorgânicas , Antibacterianos/química , Antibacterianos/farmacologia , Bandagens , Escherichia coli , Gelatina/química , Hidrogéis/química , Hidrogéis/farmacologia , Ferro/farmacologia , Estruturas Metalorgânicas/farmacologia , Metacrilatos/farmacologia , Nanogéis
4.
Toxicol Appl Pharmacol ; 408: 115263, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33022283

RESUMO

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat because there are no targeted therapies. Currently, chemotherapy is the only clinical option for TNBC despite development of resistance. New therapeutic agents with unique mechanisms of action are urgently needed; therefore, this study investigated the potential anti-TNBC effects of budlein A methylacrylate (BAM), a natural sesquiterpene lactone isolated from plants of the Helianthus genus. We discovered that BAM selectively suppressed and induced apoptosis TNBC cell growth versus other breast cancer or normal mammary epithelial cells. Mechanistically, BAM co-inhibited inhibitor of nuclear factor κBα (IκBα) kinase subunit ß (IKKß) and exportin-1 (XPO-1; chromosome region maintenance 1, CRM1), which are two dysregulated onco-related proteins in TNBC cells, by covalently modifying key functional cysteine residues (Cys179 of IKKß, Cys528 of XPO-1). Dual inhibition led to the stabilization and nuclear retention of IκBα, impairment of NF-κB transcriptional activity, and consequent induction of TNBC cell apoptosis. In conclusion, this study provides evidence that co-inhibition of IKKß and XPO-1 by BAM was effective against TNBC, demonstrating it as a representative new generation inhibitor with potential for TNBC treatment.


Assuntos
Antineoplásicos/uso terapêutico , Quinase I-kappa B/antagonistas & inibidores , Carioferinas/antagonistas & inibidores , Lactonas/uso terapêutico , Metacrilatos/uso terapêutico , Sesquiterpenos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Quinase I-kappa B/genética , Carioferinas/genética , Lactonas/farmacologia , Metacrilatos/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Sesquiterpenos/farmacologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
5.
Sci Rep ; 9(1): 13621, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541129

RESUMO

Cerebral malaria pathogenesis involves vascular dysfunction with low nitric oxide (NO) bioavailability, vasoconstriction and impaired vasodilation, leading to ischemia, tissue hypoxia and ultimately death. Cerebral blood flow (CBF) involves NO and other pathways, including arachidonic acid (AA)-derived metabolites. Here we show that mice with experimental cerebral malaria (ECM) by P. berghei ANKA showed marked decreases in CBF (as assessed by laser speckle contrast imaging - LSCI) and that administration of L-arginine supplementation (50 mg/kg) and/or of the thromboxane synthase inhibitor Ozagrel (100 mg/kg) induced immediate increases in CBF. L-arginine in combination with artesunate (32 mg/kg) induced immediate reversal of brain ischemia in the short-term (1 hour), but the effect subsided after 3 and 6 hours. Neither L-arginine nor Ozagrel reversed blood brain barrier breakdown. Mice with ECM showed brain levels of selected AA-derived metabolites with a vasoconstrictor profile, with increased levels of 8-isoprostanes, 20-HETE and 14,15-DHET, whereas mice infected with a non-ECM-inducing strain of P. berghei (NK65) showed a vasodilator profile, with normal levels of 20-HETE and 14,15-DHET and increased levels of PGE2. L-arginine is capable of partially reversing cerebral ischemia and AA metabolites may play a role in the cerebrovascular dysfunction in ECM.


Assuntos
Arginina/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Malária Cerebral/patologia , Animais , Arginina/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/patologia , Suplementos Nutricionais , Feminino , Malária Cerebral/metabolismo , Metacrilatos/metabolismo , Metacrilatos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Plasmodium berghei/efeitos dos fármacos , Tromboxano-A Sintase/antagonistas & inibidores , Tromboxano-A Sintase/metabolismo , Tromboxanos/antagonistas & inibidores , Tromboxanos/metabolismo , Vasoconstrição/efeitos dos fármacos
6.
Mater Sci Eng C Mater Biol Appl ; 104: 109916, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499946

RESUMO

Composite resins (CRs) are widely used as dental restorative materials for caries treatment. They cause problems of secondary caries since Streptococcus mutans stays in the dental plaque, which the surface exists and produces acidic compounds during metabolism. The dental plaque depositions are induced by the protein adsorption on the surface. Therefore, suppression of protein adsorption on the surface of the CRs is important for inhibiting the formation of plaque and secondary caries. In this study we developed a surface treatment to provide an antibiofouling nature to the CRs by chemical reaction with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers in the oral cavity during dental treatment. To carry out the photochemical reaction on the remaining polymerizable groups of CRs, we synthesized the MPC polymer with a polymerizable group in the side chain. The MPC polymer could bind on the surfaces of the CRs chemically under dental treatment procedures. The treated surface showed significant resistance to oral protein adsorption and bacterial adhesion even when the surface was brushed with a toothbrush. Thus, we concluded that the photochemical reaction of the MPC polymer with the CRs in the oral cavity was good for making an antibiofouling surface and preventing secondary caries.


Assuntos
Resinas Acrílicas/farmacologia , Resinas Compostas/farmacologia , Placa Dentária/prevenção & controle , Metacrilatos/farmacologia , Fosforilcolina/análogos & derivados , Polímeros/farmacologia , Poliuretanos/farmacologia , Incrustação Biológica , Mucinas/metabolismo , Fósforo/análise , Fosforilcolina/farmacologia , Espectroscopia Fotoeletrônica , Polímeros/síntese química , Polímeros/química , Espectroscopia de Prótons por Ressonância Magnética , Silício/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Streptococcus mutans/efeitos dos fármacos , Propriedades de Superfície
7.
ACS Appl Mater Interfaces ; 11(19): 17234-17246, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31008576

RESUMO

Due to the great similarity to the natural extracellular matrix and minimally invasive surgeries, injectable hydrogels are appealing biomaterials in cartilage and bone tissue engineering. Nevertheless, undesirable mechanical properties and bioactivity greatly hamper their availability in clinic applications. Here, we developed an injectable nanocomposite hydrogel by in situ growth of CaP nanoparticles (ICPNs) during the free-radical polymerization of dimethylaminoethyl methacrylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) matrix (PDH) for bone regeneration. The ICPNs are self-assembled by incorporation of poly-l-glutamic acid (PGA) with abundant carboxyl functional groups during the formation of carboxyl-Ca2+ coordination and further CaP precipitation. Furthermore, the carboxyl groups of PGA could interact with the tertiary amines of DMAEMA fragments and thus improve the mechanical strength of hydrogels. Upon mixing solutions of DMAEMA and HEMA bearing PGA, Ca2+, and PO43-, this effective and dynamic coordination led to the rapid self-assembly of CaP NPs and PDH nanocomposite hydrogels (PDH/mICPN). The obtained optimal nanocomposite hydrogels exhibited suitable injectable time, an enhanced tensile strength of 321.1 kPa, and a fracture energy of 29.0 kJ/m2 and dramatically facilitated cell adhesion and upregulated osteodifferentiation compared to hydrogels prepared by blending ex situ prefabricated CaP NPs. In vivo experiments confirmed the promoted osteogenesis, which shows a striking contrast to pure PDH hydrogels. Additionally, the methacrylate groups on the monomers could easily be functionalized with aptamers and thereby facilitate recognition and capturing of bone marrow stromal cells both in vitro and in vivo and strengthen the bone regeneration. We believe that our conducted research about in situ self-assembled CaP nanoparticle-coordinated hydrogels will open a new avenue for bone regeneration in the future endeavors.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Hidrogéis/farmacologia , Osteogênese/efeitos dos fármacos , Engenharia Tecidual , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/fisiologia , Cálcio/química , Cartilagem/efeitos dos fármacos , Cartilagem/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Hidrogéis/síntese química , Hidrogéis/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Metacrilatos/química , Metacrilatos/farmacologia , Nanopartículas/química , Fósforo/química , Ratos
8.
ACS Appl Mater Interfaces ; 11(13): 12283-12297, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30864429

RESUMO

The emergence of nontoxic, eco-friendly, and biocompatible polymers derived from natural sources has added a new and exciting dimension to the development of low-cost and scalable biomaterials for tissue engineering applications. Here, we have developed a mechanically strong and durable hydrogel composed of an eco-friendly biopolymer that exists within the cell walls of fruits and plants. Its trade name is pectin, and it bears many similarities with natural polysaccharides in the native extracellular matrix. Specifically, we have employed a new pathway to transform pectin into a ultraviolet (UV)-cross-linkable pectin methacrylate (PEMA) polymer. To endow this hydrogel matrix with cell differentiation and cell spreading properties, we have also incorporated thiolated gelatin into the system. Notably, we were able to fine-tune the compressive modulus of this hydrogel in the range ∼0.5 to ∼24 kPa: advantageously, our results demonstrated that the hydrogels can support growth and viability for a wide range of three-dimensionally (3D) encapsulated cells that include muscle progenitor (C2C12), neural progenitor (PC12), and human mesenchymal stem cells (hMSCs). Our results also indicate that PEMA-gelatin-encapsulated hMSCs can facilitate the formation of bonelike apatite after 5 weeks in culture. Finally, we have demonstrated that PEMA-gelatin can yield micropatterned cell-laden 3D constructs through UV light-assisted lithography. The simplicity, scalability, processability, tunability, bioactivity, and low-cost features of this new hydrogel system highlight its potential as a stem cell carrier that is capable of bridging the gap between clinic and laboratory.


Assuntos
Materiais Biocompatíveis , Células Imobilizadas , Gelatina , Hidrogéis , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Metacrilatos , Pectinas , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Células Imobilizadas/citologia , Células Imobilizadas/metabolismo , Células Imobilizadas/transplante , Matriz Extracelular/química , Gelatina/química , Gelatina/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Metacrilatos/química , Metacrilatos/farmacologia , Células PC12 , Pectinas/química , Pectinas/farmacologia , Ratos
9.
Carbohydr Polym ; 206: 455-467, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553345

RESUMO

This study sought to improve the handling, stability to aqueous medium and healing properties of alginate-based three-dimensional structures to be applied as wound scaffolds. Thus, Ca-alginate was plasticized with PEG-methyl ether methacrylate (PEGMA) and blended with the freeze-dried gel of A. vera and aqueous leaves extracts of M. oleifera. Ca-alginate-PEGMA scaffolds remained structurally stable almost four times longer than pure alginate materials, while a high porous architecture required for tissue scaffolding applications was maintained after alginate plasticization with PEGMA. A. vera increased the water uptake capability of the scaffolds and M. oleifera provided antioxidant capacity, anti-inflammatory properties and antimicrobial activity against S. aureus. Blending 1% (w/v) A. vera and 1% (w/v) M. oleifera with Ca-alginate-PEGMA, significantly increased the scaffolds cell proliferation (after 10 days of evaluation), compared with scaffolds without plant extracts. The experimental results showed that Ca-alginate-PEGMA/A. vera/M. oleifera biocomposites have great potential for wound healing applications.


Assuntos
Alginatos/farmacologia , Aloe/química , Metacrilatos/farmacologia , Moringa oleifera/química , Extratos Vegetais/farmacologia , Polietilenoglicóis/farmacologia , Cicatrização/efeitos dos fármacos , Alginatos/química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Metacrilatos/química , Extratos Vegetais/química , Folhas de Planta/química , Preparações de Plantas/química , Preparações de Plantas/farmacologia , Polietilenoglicóis/química , Porosidade , Staphylococcus aureus/efeitos dos fármacos
10.
Biotechnol Bioeng ; 115(4): 1086-1095, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29280498

RESUMO

Scaffold based systems have shown significant potential in modulating immune responses in vivo. While there has been much attention on macrophage interactions with tissue engineered scaffolds for tissue regeneration, fewer studies have looked at the effects of scaffold design on the response of immune cells-that is, dendritic cells (DCs). Here, we present the effects of varying pore size of poly (2-hydroxyethyl methacrylate) (pHEMA) and poly(dimethylsiloxane) (PDMS, silicone) scaffolds on the maturation and in vivo enrichment of DCs. We employ a precision templating method to make 3-D porous polymer scaffolds with uniformly defined and adjustable architecture. Hydrophilic pHEMA and hydrophobic PDMS scaffolds were fabricated in three pore sizes (20, 40, 90 µm) to quantify scaffold pore size effects on DCs activation/maturation in vitro and in vivo. In vitro results showed that both pHEMA and PDMS scaffolds could promote maturation in the DC cell line, JAWSII, that resembled lipopolysaccharide (LPS)-activated/matured DCs (mDCs). Scaffolds with smaller pore sizes correlate with higher DC maturation, regardless of the polymer used. In vivo, when implanted subcutaneously in C57BL/6J mice, scaffolds with smaller pore sizes also demonstrated more DCs recruitment and more sustained activation. Without the use of DC chemo-attractants or chemical adjuvants, our results suggested that DC maturation and scaffold infiltration profile can be modulated by simply altering the pore size of the scaffolds.


Assuntos
Células Dendríticas/efeitos dos fármacos , Alicerces Teciduais/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Dendríticas/química , Dimetilpolisiloxanos/química , Dimetilpolisiloxanos/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Lipopolissacarídeos/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Microesferas , Nylons/química , Nylons/farmacologia , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacologia , Porosidade
11.
Pestic Biochem Physiol ; 134: 63-72, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27914541

RESUMO

Panax ginseng C.A. Meyer is a valuable herb in China that has also gained popularity in the West because of its pharmacological properties. The constituents isolated and characterized in ginseng stems include ginsenosides, fatty acids, amino acids, volatile oils, and polysaccharides. In this study, the effects of fungicide azoxystrobin applied on antioxidant enzyme activity and ginsenosides content in ginseng stems was studied by using Panax ginseng C. A. Mey. cv. (the cultivar of Ermaya) under natural environmental conditions. The azoxystrobin formulation (25% SC) was sprayed three times on ginseng plants at different doses (150ga.i./ha and 225ga.i./ha), respectively. Two new fatty acids esters (ethyl linoleate and methyl linolenate) were firstly detected in ginseng stems by the application of azoxystrobin as foliar spray. The results indicated that activities of enzymatic antioxidants, the content of ginsenosides and two new fatty acids esters in ginseng stems in azoxystrobin-treated plants were increased. Azoxystrobin treatments to ginseng plants at all growth stages suggest that the azoxystrobin-induced delay of senescence is due to an enhanced antioxidant enzyme activity protecting the plants from harmful active oxygen species (AOS). The activity of superoxide dismutase (SOD) in azoxystrobin-treated plants was about 1-3 times higher than that in untreated plants. And the effects was more significant (P=0.05) when azoxystrobin was applied at dose of 225ga.i./ha. This work suggests that azoxystrobin plays an important role in delaying of senescence by changing physiological and biochemical indicators and increasing ginsenosides content in ginseng stems.


Assuntos
Fungicidas Industriais/farmacologia , Ácidos Linoleicos/metabolismo , Ácidos Linolênicos/metabolismo , Metacrilatos/farmacologia , Panax/efeitos dos fármacos , Caules de Planta/efeitos dos fármacos , Pirimidinas/farmacologia , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Clorofila/metabolismo , Ésteres , Ginsenosídeos/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Panax/química , Panax/metabolismo , Peroxidase/metabolismo , Proteínas de Plantas/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Estrobilurinas , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo
12.
Sci Rep ; 6: 20483, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26853908

RESUMO

Knowledge of the evolution of fungicide resistance is important in securing sustainable disease management in agricultural systems. In this study, we analyzed and compared the spatial distribution of genetic variation in azoxystrobin sensitivity and SSR markers in 140 Phytophthora infestans isolates sampled from seven geographic locations in China. Sensitivity to azoxystrobin and its genetic variation in the pathogen populations was measured by the relative growth rate (RGR) at four fungicide concentrations and determination of the effective concentration for 50% inhibition (EC50). We found that all isolates in the current study were sensitive to azoxystrobin and their EC50 was similar to that detected from a European population about 20 years ago, suggesting the risk of developing azoxystrobin resistance in P. infestans populations is low. Further analyses indicate that reduced genetic variation and high fitness cost in resistant mutations are the likely causes for the low evolutionary likelihood of developing azoxystrobin resistance in the pathogen. We also found a negative correlation between azoxystrobin tolerance in P. infestans populations and the mean annual temperature of collection sites, suggesting that global warming may increase the efficiency of using the fungicide to control the late blight.


Assuntos
Fungicidas Industriais/farmacologia , Metacrilatos/farmacologia , Repetições de Microssatélites/genética , Phytophthora infestans/efeitos dos fármacos , Pirimidinas/farmacologia , China , Resistência a Medicamentos/efeitos dos fármacos , Variação Genética , Phytophthora infestans/genética , Phytophthora infestans/crescimento & desenvolvimento , Folhas de Planta/parasitologia , Solanum tuberosum/parasitologia , Estrobilurinas , Temperatura
13.
ACS Appl Mater Interfaces ; 8(3): 1676-86, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26727696

RESUMO

The brittle structure of polymer-bioactive-glass hybrids is a hurdle for their biomedical applications. To address this issue here, we developed a novel method to cease the overcondensation of bioactive-glass by polymer cross-linking. Here, an organosilane-functionalized gelatin methacrylate (GelMA) is covalently bonded to a bioactive-glass during the sol-gel process, and the condensation of silica networks is controlled by photo-cross-linking of GelMA. The physicochemical properties and mechanical strength of these hybrids are tunable by the incorporation of secondary cross-linking agents. These hydrogels display elastic properties with ultimate compression strain above 0.2 mm·mm(-1) and tunable compressive modulus in the range of 42-530 kPa. In addition, these hydrogels are bioactive because they promoted the alkaline phosphatase activity of bone progenitor cells. They are also well-tolerated in the mice subcutaneous model. Therefore, our method is efficient for the prevention of overcondensation and allows preparation of soft bioactive hydrogels from organic-inorganic matrices, suitable for soft and hard tissue regeneration.


Assuntos
Gelatina/farmacologia , Vidro/química , Teste de Materiais/métodos , Animais , Cálcio/análise , Proliferação de Células/efeitos dos fármacos , Humanos , Implantes Experimentais , Metacrilatos/farmacologia , Camundongos , Compostos de Organossilício/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Fósforo/análise , Polietilenoglicóis/química , Silicatos/química
14.
Hereditas ; 153: 10, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28096772

RESUMO

BACKGROUND: Early blight, caused by the fungus Alternaria solani, occurs on potato mainly in the south-eastern part of Sweden, but also in other parts of the country. The aim of this study was to investigate the genetic diversity of A. solani populations from different potato growing regions in south-eastern Sweden using AFLP marker analysis. In addition, the cultured isolates were examined for substitutions in the gene encoding cytochrome b, associated with loss of sensitivity against QoI fungicides. RESULTS: Nei's gene diversity index for the Swedish populations of A. solani revealed a gene diversity of up to 0.20. Also genetic differentiation was observed among populations of A. solani from different locations in south-eastern Sweden. The mitochondrial genotype of the isolates of A. solani was determined and both known genotypes, GI (genotype 1) and GII (genotype 2), were found among the isolates. The occurrence of the F129L substitution associated with a loss of sensitivity to strobilurins was confirmed among the GII isolates. In vitro conidial germination tests verified that isolates containing the F129L substitution had reduced sensitivity to azoxystrobin and, at a lower extent, to pyraclostrobin. CONCLUSIONS: Genetic diversity was relatively high among isolates of A. solani in south-eastern part of Sweden. F129L substitutions, leading to reduced sensitivity to strobilurins, have been established in field populations, which may have implications for the future efficacy of QoI fungicides.


Assuntos
Alternaria/genética , Farmacorresistência Fúngica/genética , Variação Genética , Alternaria/efeitos dos fármacos , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Carbamatos/farmacologia , Citocromos b/genética , DNA Fúngico/genética , Fungicidas Industriais/farmacologia , Genótipo , Metacrilatos/farmacologia , Mitocôndrias/genética , Doenças das Plantas/microbiologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Solanum tuberosum/microbiologia , Estrobilurinas , Suécia
15.
Nanoscale ; 7(43): 18119-28, 2015 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-26471016

RESUMO

We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic anticancer treatment. The unique multiple anchoring groups can be used to substantially improve the affinity of the ligands to the surfaces of the nanoparticles to form ultrastable iron oxide nanoparticles with control over their hydrodynamic diameter and interfacial chemistry. Thus the BTZ-incorporated-bio-inspired-smart magnetic nanoplatform will act as a hyperthermic agent that delivers heat when an alternating magnetic field is applied while the BTZ-bound catechol moieties act as chemotherapeutic agents in a cancer environment by providing pH-dependent drug release for the synergistic thermo-chemotherapy application. The anticancer efficacy of these bio-inspired multifunctional smart magnetic nanoparticles was tested both in vitro and in vivo and found that these unique magnetic nanoplatforms can be established to endow for the next generation of nanomedicine for efficient and safe cancer therapy.


Assuntos
Antineoplásicos , Bortezomib , Sistemas de Liberação de Medicamentos/métodos , Compostos Férricos , Hipertermia Induzida/métodos , Campos Magnéticos , Nanopartículas/química , Neoplasias/terapia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Bortezomib/química , Bortezomib/farmacologia , Linhagem Celular Tumoral , Compostos Férricos/química , Compostos Férricos/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Camundongos , Células NIH 3T3
16.
Biomacromolecules ; 15(7): 2725-34, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-24955658

RESUMO

Oral drug delivery is a route of choice for vaccine administration because of its noninvasive nature and thus efforts have focused on efficient delivery of vaccine antigens to mucosal sites. An effective oral vaccine delivery system must protect the antigen from degradation upon mucosal delivery, penetrate mucosal barriers, and control the release of the antigen and costimulatory and immunomodulatory agents to specific immune cells (i.e., APCs). In this paper, mannan-modified pH-responsive P(HEMA-co-MAA) nanogels were synthesized and assessed as carriers for oral vaccination. The nanogels showed pH-sensitive properties, entrapping and protecting the loaded cargo at low pH values, and triggered protein release after switching to intestinal pH values. Surface decoration with mannan as carbohydrate moieties resulted in enhanced internalization by macrophages as well as increasing the expression of relevant costimulatory molecules. These findings indicate that mannan-modified P(HEMA-co-MAA) nanogels are a promising approach to a more efficacious oral vaccination regimen.


Assuntos
Portadores de Fármacos/química , Metacrilatos/química , Administração Oral , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Géis , Concentração de Íons de Hidrogênio , Cinética , Mananas/química , Metacrilatos/farmacologia , Camundongos , Nanoestruturas/química , Propriedades de Superfície , Vacinas/administração & dosagem , Vacinas/química
17.
Free Radic Biol Med ; 67: 408-15, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24334251

RESUMO

Nutrient deprivation is a stimulus for oxidative stress and is an established method for induction of cell autophagy and apoptosis. The aims of this study were to identify conditions that evoke superoxide production in cultured human umbilical vein endothelial cells (HUVECs), determine the mechanism of action for this response, and examine whether the stimulus might facilitate the adhesion of human isolated neutrophils to the HUVECs. HUVECs were incubated in M199 medium under conditions of serum starvation (serum-free M199 medium), low serum (medium containing 2% fetal calf serum), and high serum (medium containing 20% fetal calf serum). HUVECs were also incubated under proinflammatory conditions, in medium supplemented with 50ng/ml tumor necrosis factor-α (TNF-α) or neutrophils preactivated with 10nM phorbol 12-myristate 13-acetate (PMA). Superoxide production was increased fourfold in serum-starved HUVECs compared to cells incubated in 20% medium, and this was reduced by inhibitors of the mitochondrial electron transport chain and mitochondrial Ca(2+) uniporter. Superoxide production was 23.6% higher in HUVECs incubated with TNF-α in 2% medium compared to 2% medium alone, but unchanged with TNF-α in 20% medium. PMA-activated neutrophils adhered to morphologically aberrant HUVECs, which were mainly evident under the low-serum condition. The findings show a role of mitochondrial enzymes in superoxide production in response to nutrient deprivation and suggest that proinflammatory responses in HUVECs become manifest when HUVECs are in an already-compromised state.


Assuntos
Meios de Cultura Livres de Soro/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Superóxidos/metabolismo , Canais de Cálcio/metabolismo , Adesão Celular , Técnicas de Cocultura , Meios de Cultura Livres de Soro/química , Complexo de Proteínas da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Metacrilatos/farmacologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Rutênio Vermelho/farmacologia , Superóxidos/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Tiazóis/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
18.
J Biomed Mater Res A ; 102(5): 1342-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23720384

RESUMO

Aromatic poly(ether ether ketone) (PEEK) is a super engineering plastic, which has good mechanical properties and is resistant to physical and chemical stimuli. We have, therefore, attempted to use PEEK in cardiovascular devices. Synthetic cardiovascular devices require both high hemocompatibility and anti-inflammatory activity in addition to the mechanical properties. We modified the PEEK surface by photoinduced and self-initiated graft polymerization with 2-methacryloyloxyethyl phosphorylcholine (MPC; PMPC-grafted PEEK) for obtaining good antithrombogenicity. Polymerization was carried out on the surface of PEEK under radiation of ultraviolet (UV) light during which we controlled monomer concentrations, temperatures, and UV intensities. The biological performance of the PMPC-grafted PEEK was examined and compared with that of unmodified PEEK. With increase in the thickness of the PMPC layer, the amount of fibrinogen adsorption decreased significantly in comparison to that in the case of unmodified PEEK. When placed in contact with human platelet-rich plasma, surface of the PMPC-grafted PEEK clearly showed inhibition of platelet adhesion and activation. Also, bacterial adhesion was reduced dramatically on the PMPC-grafted PEEK. Thus, the PMPC grafting on PEEK improved the antithrombogenicity.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Escherichia coli/citologia , Cetonas/farmacologia , Metacrilatos/farmacologia , Fosforilcolina/análogos & derivados , Adesividade Plaquetária/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Polimerização/efeitos da radiação , Raios Ultravioleta , Adsorção , Benzofenonas , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Plaquetas/ultraestrutura , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Fibrinogênio/metabolismo , Fibrinogênio/ultraestrutura , Humanos , Cetonas/química , Metacrilatos/química , Fósforo/análise , Fosforilcolina/química , Fosforilcolina/farmacologia , Espectroscopia Fotoeletrônica , Polietilenoglicóis/química , Polimerização/efeitos dos fármacos , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Água/química
19.
Pest Manag Sci ; 69(1): 35-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22761173

RESUMO

BACKGROUND: Cercospora leaf spot (CLS), caused by the fungus Cercospora beticola, is the most serious foliar disease of sugar beet (Beta vulgaris L.) worldwide. Disease control is mainly achieved by timely fungicide applications. In 2011, CLS control failures were reported in spite of application of quinone outside inhibitor (QoI) fungicide in several counties in Michigan, United States. The purpose of this study was to confirm the resistant phenotype and identify the molecular basis for QoI resistance of Michigan C. beticola isolates. RESULTS: Isolates collected in Michigan in 1998 and 1999 that had no previous exposure to the QoI fungicides trifloxystrobin or pyraclostrobin exhibited QoI EC(50) values of ≤ 0.006 µg mL(-1) . In contrast, all isolates obtained in 2011 exhibited EC(50) values of > 0.92 µg mL(-1) to both fungicides and harbored a mutation in cytochrome b (cytb) that led to an amino acid exchange from glycine to alanine at position 143 (G143A) compared with baseline QoI-sensitive isolates. Microsatellite analysis of the isolates suggested that QoI resistance emerged independently in multiple genotypic backgrounds at multiple locations. A real-time PCR assay utilizing dual-labeled fluorogenic probes was developed to detect and differentiate QoI-resistant isolates harboring the G143A mutation from sensitive isolates. CONCLUSION: The G143A mutation in cytb is associated with QoI resistance in C. beticola. Accurate monitoring of this mutation will be essential for fungicide resistance management in this pathosystem.


Assuntos
Ascomicetos/genética , Citocromos b/genética , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Fungicidas Industriais/farmacologia , Doenças das Plantas/microbiologia , Mutação Puntual/efeitos dos fármacos , Acetatos/farmacologia , Ascomicetos/efeitos dos fármacos , Ascomicetos/isolamento & purificação , Beta vulgaris/microbiologia , Carbamatos/farmacologia , Citocromos b/metabolismo , Proteínas Fúngicas/metabolismo , Iminas/farmacologia , Metacrilatos/farmacologia , Michigan , Repetições de Microssatélites , Pirazóis/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Estrobilurinas
20.
Langmuir ; 28(49): 17011-8, 2012 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-23157582

RESUMO

It is well known that adsorbed proteins play a major role in cell adhesion. However, it has also been reported that cells can adhere to a protein-resistant surface. In this work, the behavior of L02 and BEL-7402 cells on a protein-resistant, 3D topographical surface was investigated. The topographical gold nanoparticle layer (GNPL) surfaces were prepared by chemical gold plating, and the topography was described by roughness parameters acquired from a multiscale analysis. Both smooth Au and GNPL surfaces were modified with POEGMA polymer brushes using surface-initiated ATRP. The dry and hydrated thicknesses of POEGMA brushes on both smooth and rough surfaces were measured by AFM using a nanoindentation method. Protein adsorption experiments using (125)I radiolabeling revealed similarly low levels of protein adsorption on smooth and GNPL surfaces modified with POEGMA, thus allowing an investigation of the effects of topography on cell behavior under conditions of minimal protein adsorption. The roles of VN and FN adsorption in both L02 cells and BEL-7402 cells adhesion were investigated using cell culturing with and without a serum supplement. It was found that initial cell adhesion occurred via proteins adsorbed from the cell culture medium, whereas subsequent durable cell adhesion could be attributed to the topographical structure of the surface. Although cell spreading on protein-resistant surfaces was constrained because of the lack of adsorbed proteins, we found that cells adherent to topographical surfaces were more firmly attached and thus were more durable compared to those on smooth surfaces. In general, however, we conclude that topography is more important for cell adhesion on a protein-resistant surface.


Assuntos
Materiais Revestidos Biocompatíveis/química , Ouro/química , Hepatócitos/efeitos dos fármacos , Nanopartículas Metálicas/química , Metacrilatos/química , Polietilenoglicóis/química , Albumina Sérica/química , Adsorção , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/farmacologia , Hepatócitos/citologia , Humanos , Radioisótopos do Iodo , Nanopartículas Metálicas/ultraestrutura , Metacrilatos/farmacologia , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos , Propriedades de Superfície
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