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The first total syntheses of polycyclic diterpenes phomopsene (1), methyl phomopsenonate (2), and iso-phomopsene (3) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1-3. This work enables us to determine that the correct structure of iso-phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.
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Many metal nanoparticles are reported to have intrinsic enzyme-like activities and offer great potential in chemical and biomedical applications. In this study, PtCu alloy nanoparticles (NPs), synthesized through hydrothermal treatment of Cu2+ and Pt2+ in an aqueous solution, were evaluated for ferroxidase-like and antibacterial activity. Electron spin resonance (ESR) spectroscopy and colorimetric methods were used to demonstrate that PtCu NPs exhibited strong ferroxidase-like activity in a weakly acidic environment and that this activity was not affected by the presence of most other ions, except silver. Based on the color reaction of salicylic acid in the presence of Fe3+, we tested the ferroxidase-like activity of PtCu NPs to specifically detect Fe2+ in a solution of an oral iron supplement and compared these results with data acquired from atomic absorption spectroscopy and the phenanthroline colorimetric method. The results showed that the newly developed PtCu NPs detection method was equivalent to or better than the other two methods used for Fe2+ detection. The antibacterial experiments showed that PtCu NPs have strong antibacterial activity against Staphylococcus aureus and Escherichia coli. Herein, we demonstrate that the peroxidase-like activity of PtCu NPs can catalyze H2O2 and generate hydroxyl radicals, which may elucidate the antibacterial activity of the PtCu NPs against S. aureus and E. coli. These results showed that PtCu NPs exhibited both ferroxidase- and peroxidase-like activity and that they may serve as convenient and efficient NPs for the detection of Fe2+ and for antibacterial applications.
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Antibacterianos/toxicidade , Ceruloplasmina/toxicidade , Nanopartículas Metálicas/toxicidade , Ligas/toxicidade , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacosRESUMO
Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100 nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H2O2. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.
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Trato Gastrointestinal/efeitos dos fármacos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Sobrevivência Celular , Trato Gastrointestinal/fisiologia , Humanos , Peróxido de Hidrogênio , Radical Hidroxila , Tamanho da Partícula , PermeabilidadeRESUMO
BACKGROUND: Nanomaterials that exhibit intrinsic enzyme-like characteristics have shown great promise as potential antibacterial agents. However, many of them exhibit inefficient antibacterial activity and biosafety problems that limit their usefulness. The development of new nanomaterials with good biocompatibility and rapid bactericidal effects is therefore highly desirable. Here, we show a new type of terbium oxide nanoparticles (Tb4O7 NPs) with intrinsic oxidase-like activity for in vitro and in vivo antibacterial application. RESULTS: We find that Tb4O7 NPs can quickly oxidize a series of organic substrates in the absence of hydrogen peroxide. The oxidase-like capacity of Tb4O7 NPs allows these NPs to consume antioxidant biomolecules and generate reactive oxygen species to disable bacteria in vitro. Moreover, the in vivo experiments showed that Tb4O7 NPs are efficacious in wound-healing and are protective of normal tissues. CONCLUSIONS: Our results reveal that Tb4O7 NPs have intrinsic oxidase-like activity and show effective antibacterial ability both in vitro and in vivo. These findings demonstrate that Tb4O7 NPs are effective antibacterial agents and may have a potential application in wound healing.
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Antibacterianos/química , Escherichia coli , Nanopartículas Metálicas/química , Óxidos/química , Oxirredutases/química , Staphylococcus aureus , Térbio/química , Cicatrização , Animais , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Sobrevivência Celular , Escherichia coli/efeitos dos fármacos , Hemólise , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos Endogâmicos BALB C , Óxidos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Térbio/farmacologiaRESUMO
Noble metal nanoparticles (NPs) have been widely used in many consumer products. Their effects on the antioxidant activity of commercial dietary supplements have not been well evaluated. In this study, we examined the effects of gold (Au NPs), silver (Ag NPs), platinum (Pt NPs), and palladium (Pd NPs) on the hydroxyl radical (·OH) scavenging ability of three dietary supplements vitamin C (L-ascorbic acid, AA), (-)-epigallocatechin gallate (EGCG), and gallic acid (GA). By electron spin resonance (ESR) spin-trapping measurement, the results show that these noble metal NPs can inhibit the hydroxyl radical scavenging ability of these dietary supplements.
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Antioxidantes/metabolismo , Suplementos Nutricionais , Sequestradores de Radicais Livres/metabolismo , Radical Hidroxila/metabolismo , Nanopartículas Metálicas/análise , Ácido Ascórbico/metabolismo , Catequina/análogos & derivados , Catequina/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Ácido Gálico/metabolismo , Ouro/metabolismo , Paládio/metabolismo , Platina/metabolismo , Prata/metabolismoRESUMO
Recent studies showed that melanin-mimetic catechol-chitosan films are redox-active and their ability to exchange electrons confers pro-oxidant activities for the sustained, in situ generation of reactive oxygen species for antimicrobial bandages. Here we electrofabricated catechol-chitosan films, demonstrate these films are redox-active, and show their ability to exchange electrons confers sustained radical scavenging activities that could be useful for protective coatings. Electrofabrication was performed in two steps: cathodic electrodeposition of a chitosan film followed by anodic grafting of catechol to chitosan. Spectroelectrochemical reverse engineering methods were used to characterize the catechol-chitosan films and demonstrate the films are redox-active and can donate electrons to quench oxidative free radicals and can accept electrons to quench reductive free radicals. Electrofabricated catechol-chitosan films that were peeled from the electrode were also shown to be capable of donating electrons to quench an oxidative free radical, but this radical scavenging activity decayed upon depletion of electrons from the film (i.e., as the film became oxidized). However, the radical scavenging activity could be recovered by a regeneration step in which the films were contacted with the biological reducing agent ascorbic acid. These results demonstrate that catecholic materials offer important redox-based and context-dependent properties for possible applications as protective coatings.
Assuntos
Materiais Biomiméticos/química , Catecóis/química , Quitosana/química , Sequestradores de Radicais Livres/químicaRESUMO
The combination of semiconductor and plasmonic nanostructures, endowed with high efficiency light harvesting and surface plasmon confinement, has been a promising way for efficient utilization of solar energy. Although the surface plasmon resonance (SPR) assisted photocatalysis has been extensively studied, the photochemical mechanism, e.g. the effect of SPR on the generation of reactive oxygen species and charge carriers, is not well understood. In this study, we take Au@TiO2 nanostructures as a plasmonic photocatalyst to address this critical issue. The Au@TiO2 core/shell nanostructures with tunable SPR property were synthesized by the templating method with post annealing thermal treatment. It was found that Au@TiO2 nanostructures exhibit enhanced photocatalytic activity in either sunlight or visible light (λ > 420 nm). Electron spin resonance spectroscopy with spin trapping and spin labeling was used to investigate the enhancing effect of Au@TiO2 on the photo-induced reactive oxygen species and charge carriers. The formation of Au@TiO2 core/shell nanostructures resulted in a dramatic increase in light-induced generation of hydroxyl radicals, singlet oxygen, holes and electrons, as compared with TiO2 alone. This enhancement under visible light (λ > 420 nm) irradiation may be dominated by SPR induced local electrical field enhancement, while the enhancement under sunlight irradiation is dominated by the higher electron transfer from TiO2 to Au. These results unveiled that the superior photocatalytic activity of Au@TiO2 nanostructures correlates with enhanced generation of reactive oxygen species and charge carriers.
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BACKGROUND: Gold nanoparticles (AuNPs) are attracting interest as potential therapeutic agents to treat inflammatory diseases, but their anti-inflammatory mechanism of action is not clear yet. In addition, the effect of orally administered AuNPs on gut microbiota has been overlooked so far. Here, we evaluated the therapeutic and gut microbiota-modulating effects, as well as the anti-inflammatory paradigm, of AuNPs with three different coatings and five difference sizes in experimental mouse colitis and RAW264.7 macrophages. RESULTS: Citrate- and polyvinylpyrrolidone (PVP)-stabilized 5-nm AuNPs (Au-5 nm/Citrate and Au-5 nm/PVP) and tannic acid (TA)-stabilized 5-, 10-, 15-, 30- and 60-nm AuNPs were intragastrically administered to C57BL/6 mice daily for 8 days during and after 5-day dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed more marked anti-colitis effects by oral administration of Au-5 nm/Citrate and Au-5 nm/PVP, when compared to TA-stabilized AuNPs. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of leukocyte and lymphocyte, Au-5 nm/Citrate and Au-5 nm/PVP attenuated colonic and systemic inflammation more effectively than TA-stabilized AuNPs. High-throughput sequencing of fecal 16S rRNA indicated that AuNPs could induce gut dysbiosis in mice by decreasing the α-diversity, the Firmicutes/Bacteroidetes ratio, certain short-chain fatty acid-producing bacteria and Lactobacillus. Based on in vitro studies using RAW264.7 cells and electron spin resonance oximetry, AuNPs inhibited lipopolysaccharide (LPS)-triggered inducible nitric oxide (NO) synthase expression and NO production via reduction of Toll-like receptor 4 (TLR4), and attenuated LPS-induced nuclear factor kappa beta activation and proinflammatory cytokine production via both TLR4 reduction and catalytic detoxification of peroxynitrite and hydrogen peroxide. CONCLUSIONS: AuNPs have promising potential as anti-inflammatory agents; however, their therapeutic applications via the oral route may have a negative impact on the gut microbiota.
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Colite/prevenção & controle , Disbiose/etiologia , Trato Gastrointestinal/patologia , Ouro/administração & dosagem , Inflamação/patologia , Nanopartículas Metálicas/administração & dosagem , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/metabolismo , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Sulfato de Dextrana , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Filogenia , Células RAW 264.7 , Eletricidade EstáticaRESUMO
As a widely used nanomaterial in daily life, silver nanomaterials may cause great concern to female reproductive system as they are found to penetrate the blood-placental barrier and gain access to the ovary. However, it is largely unknown about how silver nanomaterials influence ovarian physiology and functions such as hormone production. This study performs in vitro toxicology study of silver nanomaterials, focusing especially on cytotoxicity and steroidogenesis and explores their underlying mechanisms. This study exposes primary rat granulosa cells to gold nanorod core/silver shell nanostructures (Au@Ag NRs), and compares outcomes with cells exposed to gold nanorods. The Au@Ag NRs generate more reactive oxygen species and reduce mitochondrial membrane potential and less production of adenosine triphosphate. Au@Ag NRs promote steroidogenesis, including progesterone and estradiol, in a time- and dose-dependent manner. Chemical reactivity and transformation of Au@Ag NRs are then studied by electron spin resonance spectroscopy and X-ray absorption near edge structure, which analyze the generation of free radical and intracellular silver species. Results suggest that both particle-specific activity and intracellular silver ion release of Au@Ag NR contribute to the toxic response of granulosa cells.
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Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Nanoestruturas/toxicidade , Nanotubos/química , Prata/química , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Iron oxide/Pd hybrid nanostructures with controllable Pd loading from 0.05 to 1.0 (calculated as Pd/Fe molar ratio) have been synthesized by chemical reduction of Pd2+ on iron oxide particles. The combination of iron oxide and Pd exhibits enhanced peroxidase-like activity and catalytic activity toward reduction of 4-nitrophenol. The catalytic enhancements were found to be dependent on the Pd loading amount as well as the synergistic effect between iron oxide and Pd. These results suggest that iron oxide with unique surface chemical state can be an active supporter and suggest an effective way to design superior hybrid nanostructures for catalytic applications.
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Compostos Férricos , Nanoestruturas , Nitrofenóis/química , Chumbo/química , Peroxidase , PeroxidasesRESUMO
Research on noble metal nanoparticles (NPs) able to scavenge reactive oxygen species (ROS) has undergone a tremendous growth recently. However, the interactions between ruthenium nanoparticles (Ru NPs) and ROS have never been systematically explored thus far. This research focused on the decomposition of hydrogen peroxide (H2O2), scavenging of hydroxyl radicals (â¢OH), superoxide radical (O2â¢-), singlet oxygen (1O2), 2,2'-azino-bis(3-ethylbenzenothiazoline- 6-sulfonic acid ion (ABTSâ¢+), and 1,1-diphenyl-2-picrylhydrazyl radical (â¢DPPH) in the presence of commercial Ru NPs using the electron spin resonance technique. In vitro cell studies demonstrated that Ru NPs have excellent biocompatibility and exert a cytoprotective effect against oxidative stress. These findings may spark fresh enthusiasm for the applications of Ru NPs under relevant physiologically conditions.
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Sequestradores de Radicais Livres/química , Nanopartículas Metálicas/química , Modelos Químicos , Espécies Reativas de Oxigênio/química , Rutênio/química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Oxigênio Singlete/química , Superóxidos/químicaRESUMO
Melanins are ubiquitous in nature but their biological activities and functions have been difficult to discern. Conventional approaches to determine material function start by resolving structure and then characterize relevant properties. These approaches have been less successful for melanins because of their complex structure and insolubility, and because their relevant properties are not readily characterized by conventional methods. Here, we report a novel spectroelectrochemical reverse engineering approach that focuses on redox and radical scavenging activities. In this method, the melanin is immobilized in a permeable hydrogel film adjacent to an electrode and this immobilized melanin is probed using diffusible mediators and complex electrical inputs. Response characteristics are measured using two modalities, electrochemical currents associated with the reaction of diffusible mediators, and optical absorbance associated with the presence of diffusible free radicals. Using this method, we observed that both Sepia and fungal melanins are redox active and can repeatedly exchange electrons to be switched between oxidized and reduced states. Further, we observed that these melanins can quench radicals either by donating or accepting electrons. Finally, we demonstrate that the melanins' radical scavenging activities are dependent on their redox state such that a melanin must be reduced to have donatable electrons to quench oxidative free radicals, or must be oxidized to accept electrons from reductive free radicals. While the observation that melanin is redox-active is consistent with their well-accepted beneficial (radical-scavenging) and detrimental (pro-oxidant) activities, these observations may also support less well-accepted proposed functions for melanin in energy harvesting and redox communication.
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Radicais Livres/química , Melaninas/química , Espécies Reativas de Oxigênio/química , Análise Espectral/métodos , Animais , Fungos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Oxirredução , SepiaRESUMO
Before graphene derivatives can be exploited as next-generation antimicrobials, we must understand their behavior under environmental conditions. Here, we demonstrate how exposure to simulated sunlight significantly enhances the antibacterial activity of graphene oxide (GO) and reveal the underlying mechanism. Our measurements of reactive oxygen species (ROS) showed that only singlet oxygen (1O2) is generated by GO exposed to simulated sunlight, which contributes only slightly to the oxidation of antioxidant biomolecules. Unexpectedly, we find the main cause of oxidation is light-induced electron-hole pairs generated on the surface of GO. These light-induced electrons promote the reduction of GO, introducing additional carbon-centered free radicals that may also enhance the antibacterial activities of GO. We conclude that GO-mediated oxidative stress mainly is ROS-independent; simulated sunlight accelerates the transfer of electrons from antioxidant biomolecules to GO, thereby destroying bacterial antioxidant systems and causing the reduction of GO. Our insights will help support the development of graphene for antibacterial applications.
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Antibacterianos/farmacologia , Grafite/farmacologia , Antibacterianos/química , Transporte de Elétrons , Elétrons , Grafite/química , Luz , ÓxidosRESUMO
In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag+) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag+ and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 µg/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag+ chelator) to the treatments significantly decreased genotoxicity of Ag+, but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag+ released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag+ can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs.
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Linfócitos/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Mutagênicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Prata/toxicidade , Acetilcisteína/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quelantes/farmacologia , Cromanos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Cinética , Linfócitos/enzimologia , Linfócitos/metabolismo , Testes para Micronúcleos , Mutagênicos/análise , Mutagênicos/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Prata/análise , Prata/química , Nitrato de Prata/antagonistas & inibidores , Nitrato de Prata/toxicidade , Solubilidade , Propriedades de SuperfícieRESUMO
The generation of reactive oxygen species (ROS) is an important mechanism of nanomaterial toxicity. We found that Prussian blue nanoparticles (PBNPs) can effectively scavenge ROS via multienzyme-like activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activity. Instead of producing hydroxyl radicals (â¢OH) through the Fenton reaction, PBNPs were shown to be POD mimetics that can inhibit â¢OH generation. We theorized for the first time that the multienzyme-like activities of PBNPs were likely caused by the abundant redox potentials of their different forms, making them efficient electron transporters. To study the ROS scavenging ability of PBNPs, a series of in vitro ROS-generating models was established using chemicals, UV irradiation, oxidized low-density lipoprotein, high glucose contents, and oxygen glucose deprivation and reperfusion. To demonstrate the ROS scavenging ability of PBNPs, an in vivo inflammation model was established using lipoproteins in Institute for Cancer Research (ICR) mice. The results indicated that PBNPs hold great potential for inhibiting or relieving injury induced by ROS in these pathological processes.
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Ferrocianetos/química , Sequestradores de Radicais Livres/química , Nanopartículas/química , Espécies Reativas de Oxigênio/química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Biomimética , Catalase/química , Ferrocianetos/farmacocinética , Ferrocianetos/farmacologia , Radical Hidroxila/química , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Peroxidases/química , Explosão Respiratória/efeitos dos fármacos , Superóxido Dismutase/química , Distribuição TecidualRESUMO
BACKGROUND: Administration of silver nanoparticles (AgNPs) to mice could result in their distribution and accumulation in multiple organs, with notable prominence in liver, lungs, and kidneys. However, how AgNPs transport through blood vesicular system to reach the target organs is unclear, and the precise differences in the mechanisms of toxicity between AgNPs and silver ions still remain elusive. In the present research, the pathological changes on these target organs with a focus on inter-endothelial junction was investigated to gain a new insight of AgNPs toxicity by comparing the mechanisms of action of AgNPs and AgNO3. METHODS: We investigated the in vitro cytotoxicity of either citrated-coated AgNPs (10, 75, and 110 nm) or silver nitrate (AgNO3) following 24 h incubations (1-40 µg/mL) in the presence of primary human umbilical vein endothelial cells (HUVEC). Meanwhile, we detected the effects of AgNPs on intercellular conjunction and intracellular ROS by VE-cadherin staining and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, respectively. To assess in vivo toxicity, we administered single or multiple intravenous injections (25 µg Ag for AgNPs and 2.5 µg Ag for AgNO3 per dose) to mice. RESULTS: In the in vitro study, the TEM observation showed that AgNPs were taken up by endothelial cells while AgNO3 was taken up little. Meanwhile AgNPs incubation induced the elevation of intracellular ROS and down-regulation of VE-cadherin between the endothelial cells and affected the cytoskeleton actin reorganization, which could be rescued by antioxidant N-acetylcysteine. In contrast, AgNO3 caused direct cell death when the concentration was higher than 20 µg/mL and without ROS induction at lower concentration. The release of AgNPs from leaking vessels induced peripheral inflammation in the liver, lungs, and kidneys, and the severity increased in proportion to the diameter of the AgNPs used. CONCLUSION: It is AgNPs but not AgNO3 that were taken up by vascular endothelial cells and induced intracellular ROS elevated, which was closely related to disruption of the integrity of endothelial layer. The AgNPs-induced leakiness of endothelial cells could mediate the common peripheral inflammation in liver, kidney and lung through intravenous exposure.
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Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Junções Intercelulares/efeitos dos fármacos , Nanopartículas Metálicas , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Prata/toxicidade , Animais , Antígenos CD/metabolismo , Antioxidantes/farmacologia , Caderinas/metabolismo , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Relação Dose-Resposta a Droga , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Injeções Intravenosas , Junções Intercelulares/metabolismo , Junções Intercelulares/patologia , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Nefrite/induzido quimicamente , Nefrite/metabolismo , Nefrite/patologia , Permeabilidade , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Pneumonia/patologia , Medição de Risco , Prata/administração & dosagem , Nitrato de Prata/toxicidade , Fatores de TempoRESUMO
BACKGROUND Currently available antithrombotic prophylaxis is not perfectly reliable in elderly patients. The aim of this retrospective study was to evaluate the efficacy and safety of Compound Danshen Tablet (CDT) in preventing thromboembolism in multiple myeloma (MM) patients treated with thalidomide-based regimens. MATERIAL AND METHODS MM patients treated with thalidomide-based regimens were retrospectively reviewed between January 2008 and March 2015. Patients were categorized into 3 cohorts based on thromboembolic prophylaxis used: CDT, Warfarin Tablet, and no prophylaxis. Venous thromboembolism (VTE), other adverse effects (AEs), and the changes of D-dimer and fibrinogen levels were monitored. RESULTS Seven out of 313 MM patients (2.24%) developed venous thrombosis events (VTE) in this retrospective study, all clustering in the no prophylaxis cohort. Three patients of the Warfarin cohort (3.19%) experienced hemorrhage. Neither VTE events nor serious AEs were observed in the CDT cohort. Following Compound Danshen or Warfarin treatment for 3 months, the D-dimer and fibrinogen levels (in particular the D-dimer level) (all P<0.05), were obviously decreased relative to their respective baselines and the no prophylaxis cohort. In contrast, the 2 blotting parameters were significantly increased in the no prophylaxis cohort relative to the baseline level (All P<0.05), and were even higher in the patients experiencing VTE compared to the no VTE patients (P<0.0001 and P=0.016, respectively). CONCLUSIONS Our findings indicate CDT is an effective therapy for preventing VTE in MM patients treated with thalidomide-based regimens, and is well tolerated in long-term use.
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Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Salvia miltiorrhiza , Tromboembolia Venosa/prevenção & controle , Adulto , Idoso , Anticoagulantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia , Estudos Retrospectivos , Fatores de Risco , Comprimidos , Talidomida/efeitos adversos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/induzido quimicamente , Varfarina/administração & dosagemRESUMO
Under evolutionary pressure from chemotherapy, cancer cells develop resistance characteristics such as a low redox state, which eventually leads to treatment failures. An attractive option for combatting resistance is producing a high concentration of produced free radicals in situ. Here, we report the production and use of dispersible hollow carbon nanospheres (HCSs) as a novel platform for delivering the drug doxorubicine (DOX) and generating additional cellular reactive oxygen species using near-infrared laser irradiation. These irradiated HCSs catalyzed sufficiently persistent free radicals to produce a large number of heat shock factor-1 protein homotrimers, thereby suppressing the activation and function of resistance-related genes. Laser irradiation also promoted the release of DOX from lysosomal DOX@HCSs into the cytoplasm so that it could enter cell nuclei. As a result, DOX@HCSs reduced the resistance of human breast cancer cells (MCF-7/ADR) to DOX through the synergy among photothermal effects, increased generation of free radicals, and chemotherapy with the aid of laser irradiation. HCSs can provide a unique and versatile platform for combatting chemotherapy-resistant cancer cells. These findings provide new clinical strategies and insights for the treatment of resistant cancers.
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Carbono/química , Doxorrubicina/química , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos , Raios Infravermelhos , Nanosferas , Espécies Reativas de Oxigênio/metabolismo , Transporte Biológico , Doxorrubicina/farmacologia , Portadores de Fármacos/metabolismo , Humanos , Lasers , Células MCF-7 , Nanosferas/metabolismoRESUMO
Colloidal molecules constructed from polymers and nanoparticles (NPs) have recently emerged as a novel class of building blocks for assembling functional hybrid materials. Particularly, self-assembly of amphiphilic block copolymer (BCP)-tethered NPs (BNPs) has shown great promise in the nanoscale design of functional hybrid materials. On the one hand, structurally the BNPs can be considered as molecular equivalents that are capable of self-assembly at multiple hierarchical levels. On the other hand, the assembly of BNPs shows significant differences from molecular assembly due to their large dimension, complex geometry, and multi-scale interactions involved in the assembly process. The manipulation of BCPs localized near the surface of the NPs offers an effective tool for engineering the interactions between NPs and hence the complexity of NP assembly. In this Feature Article, recent progresses on the self-assembly of BNPs into functional materials are summarized. First, major strategies for assembling amphiphilic BNPs are highlighted. Secondly, the application of hybrid nanostructures (e.g., vesicles) assembled from BNPs in the field of biomedical imaging and delivery is discussed. Finally, current challenges and perspectives at this frontier are outlined.