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1.
Artigo em Inglês | MEDLINE | ID: mdl-31230526

RESUMO

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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31099294

RESUMO

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.

3.
J Nanobiotechnology ; 17(1): 54, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992018

RESUMO

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.


Assuntos
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/farmacologia
4.
ACS Appl Mater Interfaces ; 11(5): 4858-4866, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30628779

RESUMO

Molybdenum disulfide (MoS2) nanosheets have received considerable interest due to their superior physicochemical performances to graphene nanosheets. As the lateral size and layer thickness decrease, the formed MoS2 quantum dots (QDs) show more promise as photocatalysts, endowing them with potential antimicrobial properties under environmental conditions. However, studies on the antibacterial photodynamic therapy of MoS2 QDs have rarely been reported. Here, we show that MoS2 QDs more effectively promote the creation and separation of electron-hole pair than MoS2 nanosheets, resulting in the formation of multiple reactive oxygen species (ROS) under simulated solar light irradiation. As a result, photoexcited MoS2 QDs show remarkably enhanced antibacterial activity, and the ROS-mediated oxidative stress plays a dominant role in the antibacterial mechanism. The in vivo experiments showed that MoS2 QDs are efficacious in wound healing under simulated solar light irradiation and exert protective effects on normal tissues, suggesting good biocompatibility properties. Our findings provide a full description of the photochemical behavior of MoS2 QDs and the resulting antibacterial activity, which might advance the development of MoS2-based nanomaterials as photodynamic antibacterial agents under environmental conditions.


Assuntos
Antibacterianos , Dissulfetos , Molibdênio , Pontos Quânticos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/química , Dissulfetos/farmacologia , Dissulfetos/toxicidade , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Molibdênio/química , Molibdênio/farmacologia , Molibdênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Processos Fotoquímicos , Pontos Quânticos/química , Pontos Quânticos/efeitos da radiação , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio , Infecção dos Ferimentos
5.
Nat Commun ; 10(1): 219, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644406

RESUMO

The oriented attachment of small nanoparticles (NPs) is recognized as an important mechanism involved in the growth of inorganic nanocrystals. However, non-oriented attachment of dissimilar NPs has been rarely observed in dispersion. This communication reports a welding phenomenon occurred directly between as-synthesized dispersions of single-component Au and chalcogenide NPs, which leads to the formation of asymmetric Au-chalcogenide hybrid NPs (HNPs). The welding of dissimilar NPs in dispersion is mainly driven by the ligand desorption-induced conformal contact between NPs and the diffusion of Au into chalcogenide NPs. The welding process can occur between NPs with distinct shapes or different capping agents or in different solvent media. A two-step assembly-welding mechanism is proposed for this process, based on our in situ electron spin resonance measurements and ab initio molecular dynamics simulation. The understanding of NP welding in dispersion may lead to the development of unconventional synthetic tools for the fabrication of hybrid nanostructures with diverse applications.

6.
J Nanobiotechnology ; 16(1): 86, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30384844

RESUMO

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.

7.
Phys Chem Chem Phys ; 20(23): 16117-16125, 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29855003

RESUMO

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.

8.
Nanoscale ; 10(23): 11176-11185, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29873378

RESUMO

Nitric oxide (NO) is an endogenous bioregulator with established roles in diverse fields. The difficulty in the modulation of NO release is still a significant obstacle to achieving successful clinical applications. We report herein our initial work using electron spin resonance (ESR) spectroscopy to detect NO generated from S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) donors catalyzed by platinum nanoparticles (Pt NPs, 3 nm) under physiological conditions. With ESR spectroscopy coupled with spin trapping and spin labeling techniques, we identified that Pt NPs can significantly promote the generation of NO from SNAP and GSNO under physiological conditions. A classic NO colorimetric detection kit was also employed to verify that Pt NPs truly triggered the release of NO from its donors. Pt NPs can act as promising delivery vehicles for on-demand NO delivery based on time and dosage. These results, along with the detection of the resulting disulfide product, were confirmed with mass spectrometry. In addition, cellular experiments provided a convincing demonstration that the triggered release of NO from its donors by Pt NPs is efficient in killing human cancer cells in vitro. The catalytic mechanism was elucidated by X-ray photo-electron spectroscopy (XPS) and ultra-high performance liquid chromatography/high-resolution mass spectrometry (UHPLC-HRMS), which suggested that Pt-S bond formation occurs in the solution of Pt NPs and NO donors. Identification of Pt NPs capable of generating NO from S-nitrosothiols (RSNOs) is an important step in harnessing NO for investigations into its clinical applications and therapies.

9.
Biomacromolecules ; 19(8): 3502-3514, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-29928797

RESUMO

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.

10.
Artigo em Inglês | MEDLINE | ID: mdl-29667503

RESUMO

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.

11.
Nanomedicine (Lond) ; 13(7): 733-747, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29542368

RESUMO

AIM: To develop the potential application of carbon nanomaterials as antioxidants calls for better understanding of how the specific structure affects their antioxidant activity. MATERIALS & METHODS: Several typical carbon nanomaterials, including graphene quantum dots and fullerene derivatives were characterized and their radical scavenging activities were evaluated; in addition, the in vitro and in vivo radioprotection experiments were performed. RESULTS: These carbon nanomaterials can efficiently scavenge free radicals in a structure-dependent manner. In vitro assays demonstrate that administration of these carbon nanomaterials markedly increases the surviving fraction of cells exposed to ionizing radiation. Moreover, in vivo experiments confirm that their administration can also increase the survival rates of mice exposed to radiation. CONCLUSION: All results confirm that large, buckyball-shaped fullerenes show the strongest antioxidant properties and the best radioprotective efficiency. Our work will be useful in guiding the design and optimization of nanomaterials for potential antioxidant and radioprotection bio-applications.

12.
ACS Appl Mater Interfaces ; 10(10): 8443-8450, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29481051

RESUMO

While the antibacterial properties of silver nanoparticles (AgNPs) have been demonstrated across a spectrum of bacterial pathogens, the effects of AgNPs on the beneficial bacteria are less clear. To address this issue, we compared the antibacterial activity of AgNPs against two beneficial lactobacilli ( Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus casei) and two common opportunistic pathogens ( Escherichia coli and Staphylococcus aureus). Our results demonstrate that those lactobacilli are highly susceptible to AgNPs, while the opportunistic pathogens are not. Acidic environment caused by the lactobacilli is associated with the bactericidal effects of AgNPs. Our mechanistic study suggests that the acidic growth environment of lactobacilli promotes AgNP dissolution and hydroxyl radical (•OH) overproduction. Furthermore, increases in silver ions (Ag+) and •OH deplete the glutathione pool inside the cell, which is associated with the increase in cellular reactive oxygen species (ROS). High levels of ROS may further induce DNA damage and lead to cell death. When E. coli and S. aureus are placed in a similar acidic environment, they also become more susceptible to AgNPs. This study provides a mechanistic description of a pH-Ag+-•OH bactericidal pathway and will contribute to the responsible development of products containing AgNPs.

13.
Colloids Surf B Biointerfaces ; 163: 379-384, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29353215

RESUMO

Herein we reported Prussian blue nanoparticles (PBNPs) possess ascorbic acid oxidase (AAO)- and ascorbic acid peroxidase (APOD)-like activities, which suppressed the formation of harmful H2O2 and finally inhibited the anti-cancer efficiency of ascorbic acid (AA). This newly revealed correlation between iron and AA could provide new insight for the studies of nanozymes and free radical biology.


Assuntos
Ascorbato Oxidase/metabolismo , Ascorbato Peroxidases/metabolismo , Ácido Ascórbico/química , Ferrocianetos/química , Ferro/química , Nanopartículas/química , Catálise , Humanos , Células MCF-7 , Nanopartículas/ultraestrutura , Oxirredução
14.
Artigo em Inglês | MEDLINE | ID: mdl-29115913

RESUMO

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 (•OH), superoxide radical (O2•-), singlet oxygen (1O2), 2,2'-azino-bis(3-ethylbenzenothiazoline- 6-sulfonic acid ion (ABTS•+), and 1,1-diphenyl-2-picrylhydrazyl radical (•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.


Assuntos
Depuradores 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/química
15.
J Agric Food Chem ; 65(45): 9893-9901, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29058433

RESUMO

Although nanosized ingredients, including TiO2 nanoparticles (NPs), can be found in a wide range of consumer products, little is known about the effects these particles have on other active compounds in product matrices. These NPs can interact with reactive oxygen species (ROS), potentially disrupting or canceling the benefits expected from antioxidants. We used electron spin resonance spectrometry to assess changes in the antioxidant capacities of six dietary antioxidants (ascorbic acid, α-tocopherol, glutathione, cysteine, epicatechin, and epicatechin gallate) during exposure to P25 TiO2 and/or simulated sunlight. Specifically, we determined the ability of these antioxidants to scavenge 1-diphenyl-2-picryl-hydrazyl radical, superoxide radical, and hydroxyl radical. Exposure to simulated sunlight alone did not lead to noticeable changes in radical-scavenging abilities; however, in combination with P25 TiO2 NPs, the scavenging abilities of most antioxidants were weakened. We found glutathione to be the most resistant to treatment with sunlight and NPs among these six antioxidants.


Assuntos
Depuradores de Radicais Livres/química , Radicais Livres/química , Nanopartículas/química , Titânio/química , Depuradores de Radicais Livres/efeitos da radiação , Nanopartículas/efeitos da radiação , Luz Solar , Titânio/efeitos da radiação
16.
Biomacromolecules ; 18(12): 4084-4098, 2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29032671

RESUMO

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.


Assuntos
Radicais Livres/química , Melaninas/química , Espécies Reativas de Oxigênio/química , Análise Espectral/métodos , Animais , Fungos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Oxirredução , Sepia
17.
Environ Sci Technol ; 51(17): 10154-10161, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28771330

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Grafite/farmacologia , Antibacterianos/química , Transporte de Elétrons , Elétrons , Grafite/química , Luz , Óxidos
18.
Artigo em Inglês | MEDLINE | ID: mdl-28532274

RESUMO

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.


Assuntos
Compostos Férricos , Nanoestruturas , Nitrofenóis/química , Chumbo/química , Peroxidase , Peroxidases
19.
Chin Med J (Engl) ; 130(8): 964-971, 2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28397727

RESUMO

BACKGROUND: Th9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment. METHODS: Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture. RESULTS: Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = -2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = -8.005, P < 0.001; day 15: t = -11.857, P < 0.001; day 20: t = -5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = -5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = -4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 µg/ml: t = -0.894, P = 0.397; 10 µg/ml: t = -3.348, P = 0.019; 20 µg/ml: t = -7.639, P < 0.001). CONCLUSIONS: This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.


Assuntos
Anticorpos/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/metabolismo , Interleucina-9/antagonistas & inibidores , Interleucina-9/metabolismo , Mastócitos/metabolismo , Animais , Sistema Nervoso Central/metabolismo , Feminino , Imuno-Histoquímica , Interleucina-9/imunologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Small ; 13(10)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28009471

RESUMO

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.


Assuntos
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-Dawley
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