Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Nanomedicine ; 21: 102037, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31220596

RESUMO

Engineered nanomaterials (ENMs) as adjuvants can potentiate the adaptive immune responses to antigens by activating immune cells in three dimensional (3D) matrixes of tissues. However, few reports explored the interactions of nano-adjuvants and immune cells at 3D nano-bio interfaces. Herein we designed an alginate-calcium microsphere of macrophage cells to explore the interactions. By an extensive comparison of ENM-induced cytokines in 2D and 3D cultured cells, IL-1ß released in 3D microspheres was found to be a predictive biomarker to assess ENM-induced immune responses in vivo. Among nine representative ENMs, La2O3 boosts the highest adaptive humoral immune response, even stronger than clinically used Alum adjuvant. It could be attributed to the biotransformation of La2O3 from spherical particles into urchin-like LaPO4, resulting in strong biopersistence and NLRP3 inflammasome activation. These findings could be potentially used for the high throughput screening of nano-adjuvants from increasingly invented ENMs to speed up their clinical uses.

2.
BMC Cardiovasc Disord ; 18(1): 217, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30497387

RESUMO

BACKGROUND & AIMS: Ticagrelor has been acknowledged as a new oral antagonist of P2Y12-adenosine diphosphate receptor, as a strategy with more rapid onset as well as more significant platelet inhibition function in acute coronary syndrome (ACS) patients. The clinical benefit of ticagrelor compared with clopidogrel remains controversial. The current meta-analysis was conducted to better evaluate the role of ticagrelor in comparison of clopidogrel in treating ACS patients. METHODS: The publications involving the safety as well as the efficacy of clopidogrel versus ticagrelor were screened and identified updated to June 2018. After rigorous review, eligible randomized controlled trials (RCTs) were extracted and propensity score matching (PSM) analysis was conducted. To analyze the summary odds ratios (ORs) of the endpoints of interest, we applied Meta-analysis Revman 5.3 software. RESULTS: There were a total of 10 studies that met our inclusion criteria, of which the risk of bleeding rate (P = 0.43), MI (P = 0.14), and stroke (P = 0.70) had no association with significant differences between patients receiving ticagrelor or clopidogrel. Nonetheless, higher rate of dyspnea was observed in ticagrelor group (OR = 1.87, 95% CI: 1.70-2.05, P<0.00001 = . CONCLUSIONS: Our present findings suggest similar efficacy and safety profiles for clopidogrel and ticagrelor Ticagrelor should be considered as a valuable option to reduce the risk of bleeding, MI and stroke, whereas potentially increases the incidence of dyspnea. Given the metabolic process, ticagrelor may be a valid and even more potent antiplatelet drug than clopidogrel, as an alternative strategy in treating patients with clopidogrel intolerance or resistance.

3.
Nat Commun ; 9(1): 4416, 2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30356046

RESUMO

Increasing concerns over the possible risks of nanotechnology necessitates breakthroughs in structure-activity relationship (SAR) analyses of engineered nanomaterials (ENMs) at nano-bio interfaces. However, current nano-SARs are often based on univariate assessments and fail to provide tiered views on ENM-induced bio-effects. Here we report a multi-hierarchical nano-SAR assessment for a representative ENM, Fe2O3, by metabolomics and proteomics analyses. The established nano-SAR profile allows the visualizing of the contributions of seven basic properties of Fe2O3 to its diverse bio-effects. For instance, although surface reactivity is responsible for Fe2O3-induced cell migration, the inflammatory effects of Fe2O3 are determined by aspect ratio (nanorods) or surface reactivity (nanoplates). These nano-SARs are examined in THP-1 cells and animal lungs, which allow us to decipher the detailed mechanisms including NLRP3 inflammasome pathway and monocyte chemoattractant protein-1-dependent signaling. This study provides more insights for nano-SARs, and may facilitate the tailored design of ENMs to render them desired bio-effects.

4.
Front Chem ; 6: 192, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29915782

RESUMO

The photocatalytic activity of TiO2 based photocatalysts can be improved by structural modification and elemental doping. In this study, through rational design, one type of carbon and nitrogen co-doped TiO2 (C, N-TiO2) photocatalyst with mesoporous structure was synthesized with improved photocatalytic activity in degrading 4-nitrophenol under simulated sunlight irradiation. The photocatalytic degradation efficiency of the C, N-TiO2 was much higher than the anatase TiO2 (A-TiO2) based on absorbance and HPLC analyses. Moreover, using zebrafish embryos, we showed that the intermediate degradation compounds generated by photocatalytic degradation of 4-nitrophenol had higher toxicity than the parent compound. A repeated degradation process was necessary to render complete degradation and non-toxicity to the zebrafish embryos. Our results demonstrated the importance of evaluating the photocatalytic degradation efficiency in conjunction with the toxicity assessment of the degradation compounds.

5.
Nanotoxicology ; 12(6): 586-601, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29732938

RESUMO

Bismuth is widely used in metallurgy, cosmetic industry, and medical diagnosis and recently, bismuth nanoparticles (NPs) (BiNP) have been made and proved to be excellent CT imaging agents. Previously, we have synthesized bovine serum albumin based BiNP for imaging purpose but we found a temporary kidney injury by BiNP. Due to the reported adverse events of bismuth on human health, we extended our studies on the mechanisms for BiNP induced nephrotoxicity. Blood biochemical analysis indicated the increase in creatinine (CREA) and blood urea nitrogen (BUN), and intraluminal cast formation with cell apoptosis/necrosis was evident in proximal convoluted tubules (PCTs) of mice. BiNP induced acute kidney injury (AKI) was associated with an increase in LC3II, while the autophagic flux indicator p62 remained unchanged. Chloroquine and rapamycin were used to evaluate the role of autophagy in AKI caused by BiNP. Results showed that BiNP induced AKI was further attenuated by rapamycin, while AKI became severe when chloroquine was applied. In vitro studies further proved BiNP induced autophagy in human embryonic kidney cells 293, presented as autophagic vacuole (AV) formation along with increased levels of autophagy-related proteins including LC3II, Beclin1, and Atg12. Specifically, reactive oxygen species (ROS) generated by BiNP could be the major inducer of autophagy, because ROS blockage attenuated autophagy. Autophagy induced by BiNP was primarily regulated by AMPK/mTOR signal pathway and partially regulated by Akt/mTOR. Our study provides fundamental theory to better understand bismuth induced nephrotoxicity for better clinical application of bismuth related compounds.

6.
Small ; 14(23): e1703915, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29733549

RESUMO

Carbon nanotubes (CNTs) exhibit a number of physicochemical properties that contribute to adverse biological outcomes. However, it is difficult to define the independent contribution of individual properties without purified materials. A library of highly purified single-walled carbon nanotubes (SWCNTs) of different lengths is prepared from the same base material by density gradient ultracentrifugation, designated as short (318 nm), medium (789 nm), and long (1215 nm) SWCNTs. In vitro screening shows length-dependent interleukin-1ß (IL-1ß) production, in order of long > medium > short. However, there are no differences in transforming growth factor-ß1 production in BEAS-2B cells. Oropharyngeal aspiration shows that all the SWCNTs induce profibrogenic effects in mouse lung at 21 d postexposure, but there are no differences between tube lengths. In contrast, these SWCNTs demonstrate length-dependent antibacterial effects on Escherichia coli, with the long SWCNT exerting stronger effects than the medium or short tubes. These effects are reduced by Pluronic F108 coating or supplementing with glucose. The data show length-dependent effects on proinflammatory response in macrophage cell line and antibacterial effects, but not on collagen deposition in the lung. These data demonstrate that over the length scale tested, the biological response to highly purified SWCNTs is dependent on the complexity of the nano/bio interface.

7.
Toxicol Appl Pharmacol ; 348: 54-66, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29678448

RESUMO

Considerable effort has been made to develop nanocarriers for controlled drug delivery over the last decade, while it remains unclear how the strength of adverse drug effect will be altered when a drug is loaded on the nanocarrier. Drug-induced phospholipidosis (DIP) is characterized with excessive accumulation of phospholipids in cells and is common for cationic amphiphilic drugs (CAD). Previously, we have reported that PEGylated graphene oxide (PEG-GO) loaded with several CAD can potentiate DIP. In current study, we extended our study on newly identified phospholipidosis (PLD) inducers that had been identified from the Library of Pharmacologically Active Compounds (LOPAC), to investigate if PEO-GO loaded with these CAD can alter DIP. Twenty-two CAD were respectively loaded on PEG-GO and incubated with RAW264.7, a macrophage cell line. The results showed that when a CAD was loaded on PEG-GO, its strength of PLD induction can be enhanced, unchanged or attenuated. PEG-GO loaded with Ifenprodil exhibited the highest PEG-GO potentiation effect compared to Ifenprodil treatment alone in RAW264.7 cells, and this effect was confirmed in human hepatocellular carcinoma HepG2, another cell line model for PLD induction. Primary hepatocyte culture and spheroids mimicking in vivo conditions were used to further validate nanocarrier potentiation on DIP by Ifenprodil. Stronger phospholipid accumulation was found in PEG-GO/Ifenprodil treated hepatocytes or spheroids than Ifenprodil treatment alone. Therefore, evidences were provided by us that nanocarriers may increase the adverse drug effects and guidance by regulatory agencies need to be drafted for the safe use of nanotechnology in drug delivery.


Assuntos
Portadores de Fármacos/toxicidade , Grafite/toxicidade , Hepatócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Microscopia de Fluorescência , Nanopartículas/toxicidade , Fosfolipídeos/metabolismo , Piperidinas/toxicidade , Animais , Relação Dose-Resposta a Droga , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/ultraestrutura , Humanos , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Cultura Primária de Células , Células RAW 264.7 , Medição de Risco , Dióxido de Silício/toxicidade , Esferoides Celulares
8.
Oncol Lett ; 15(2): 2091-2096, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434910

RESUMO

The aim of the present study was to investigate the significance and values of 3.0T diffusion weighted imaging (DWI) to differentially diagnose benign and malignant space-occupying liver lesions. A total of 91 patients with liver space-occupying lesions (145 lesions) were admitted into Zhongnan Hospital of Wuhan University (Wuhan, China) from November 2015 to May 2016. Routine scanning, DWI and high-resolution T2-weighted imaging using spin-echo echo-planar imaging were performed on all patients, to compare the apparent diffusion coefficient (ADC) values of three regions of interest in lesions with normal liver tissue. The ADC values of malignant liver lesions compared with benign liver cysts demonstrated a statistically significant difference in low b-value (P<0.05) and there was also a significant difference between malignant lesion and hepatic cyst, hepatic hemangioma or hepatic abscess in middle b-value (P<0.05). The measured ADC value may be more conducive to identify the nature of the liver space-occupying lesions; as the ADC values of malignant liver lesion, liver cyst, and liver abscesses demonstrated a statistical significance in high b-value (P<0.05). The mean ADC values between malignant liver tumors compared with benign lesions indicated a statistically significant difference. In the present study, liver space-occupying lesions demonstrated different DWI features and ADC ranges, and 3.0T DWI may be a potential means to accurately determine the nature of lesions, identifying benign and malignant space-occupying lesions.

9.
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.

10.
ACS Nano ; 12(2): 1390-1402, 2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29328670

RESUMO

While two-dimensional graphene oxide (GO) is used increasingly in biomedical applications, there is uncertainty on how specific physicochemical properties relate to biocompatibility in mammalian systems. Although properties such as lateral size and the colloidal properties of the nanosheets are important, the specific material properties that we address here is the oxidation state and reactive surface groups on the planar surface. In this study, we used a GO library, comprising pristine, reduced (rGO), and hydrated GO (hGO), in which quantitative assessment of the hydroxyl, carboxyl, epoxy, and carbon radical contents was used to study the impact on epithelial cells and macrophages, as well as in the murine lung. Strikingly, we observed that hGO, which exhibits the highest carbon radical density, was responsible for the generation of cell death in THP-1 and BEAS-2B cells as a consequence of lipid peroxidation of the surface membrane, membrane lysis, and cell death. In contrast, pristine GO had lesser effects, while rGO showed extensive cellular uptake with minimal effects on viability. In order to see how these in vitro effects relate to adverse outcomes in the lung, mice were exposed to GOs by oropharyngeal aspiration. Animal sacrifice after 40 h demonstrated that hGO was more prone than other materials to generate acute lung inflammation, accompanied by the highest lipid peroxidation in alveolar macrophages, cytokine production (LIX, MCP-1), and LDH release in bronchoalveolar lavage fluid. Pristine GO showed less toxicity, whereas rGO had minimal effects. We demonstrate that the surface oxidation state and carbon radical content play major roles in the induction of toxicity by GO in mammalian cells and the lung.

11.
Environ Sci Technol ; 51(23): 13938-13948, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29121463

RESUMO

Rare earthelement nanomaterials (REE NPs) hold considerable promise, with high availability and potential applications as superconductors, imaging agents, glass additives, fertilizers additives and feed additives. These results in potential REE NP exposure to humans and the environment through different routes and adverse effects induced by biological application of these materials are becoming an increasing concern. This study investigates the cytotoxicity of REE NPs: nLa2O3, nEu2O3, nDy2O3 and nYb2O3 from 2.5 to 80 µg/mL, in macrophages. A significant difference was observed in the extent of cytotoxicity induced in macrophages by differential REE NPs. The high-atomic number materials (i.e., nYb2O3) tending to be no toxic whereas low-atomic number materials (nLa2O3 and nEu2O3 and nDy2O3) induced 75.1%, 53.6% and 20.7% dead cells. With nLa2O3 as the representative material, we demonstrated that nLa2O3 induced cellular membrane permeabilization, through the sequestration of phosphates from membrane. The further mechanistic investigation established that membrane damage induced intracellular calcium increased to 3.0- to 7.3-fold compared to control cells. This caused the sustained overload of mitochondrial calcium by approximately 2.4-fold, which regulated cell necrosis. In addition, the injury of cellular membrane led to the release of cathepsins into cytosol which also contributed to cell death. This detailed investigation of signaling pathways driving REE NP-induced toxicity to macrophages is essential for better understanding of their potential health risks to humans and the environment.


Assuntos
Macrófagos , Metais Terras Raras/toxicidade , Nanopartículas , Morte Celular , Humanos , Nanopartículas Metálicas , Mitocôndrias , Espécies Reativas de Oxigênio
13.
Part Fibre Toxicol ; 14(1): 13, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28431555

RESUMO

BACKGROUND: The wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties. RESULTS: THP-1 and BEAS-2B cells were exposed to 0-200 µg/mL MOx for 24 h, we found some toxic MOx including CoO, CuO, Ni2O3 and Co3O4, could induce reactive oxygen species (ROS) generation and cell death due to the toxic ion shedding and/or oxidative stress generation from the active surface of MOx internalized into lysosomes. We thus hypothesized that surface passivation could reduce or eliminate the toxicity of MOx. We experimented with a series of surface coating molecules and discovered that ethylenediamine tetra (methylene phosphonic acid) (EDTMP) could form stable hexadentate coordination with MOx. The coating layer can effectively reduce the surface activity of MOx with 85-99% decrease of oxidative potential, and 65-98% decrease of ion shedding. The EDTMP coated MOx show negligible ROS generation and cell death in THP-1 and BEAS-2B cells. The protective effect of EDTMP coating was further validated in mouse lungs exposed to 2 mg/kg MOx by oropharyngeal aspiration. After 40 h exposure, EDTMP coated MOx show significant decreases of neutrophil counts, lactate dehydrogenase (LDH) release, MCP-1, LIX and IL-6 in bronchoalveolar lavage fluid (BALF), compared to uncoated particles. The haematoxylin and eosin (H&E) staining results of lung tissue also show EDTMP coating could significantly reduce the pulmonary inflammation of MOx. CONCLUSIONS: The surface reactivity of MOx including ion shedding and oxidative potential is the dominated physicochemical property that is responsible for the cytotoxicity induced by MOx. EDTMP coating could passivate the surface of MOx, reduce their cytotoxicity and pulmonary hazard effects. This coating would be an effective safe design approach for a broad spectrum of toxic MOx, which will facilitate the safe use of MOx in commercial nanoproducts.


Assuntos
Materiais Revestidos Biocompatíveis/química , Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Metais Pesados/toxicidade , Organofosfonatos/química , Animais , Líquido da Lavagem Broncoalveolar/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Exposição por Inalação , Pulmão/metabolismo , Pulmão/patologia , Masculino , Nanopartículas Metálicas/química , Metais Pesados/química , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Óxidos/toxicidade , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
14.
ACS Nano ; 11(2): 1869-1883, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28177603

RESUMO

We have recently shown that the toxicological potential of GaAs and InAs particulates in cells is size- and dissolution-dependent, tending to be more pronounced for nano- vs micron-sized particles. Whether the size-dependent dissolution and shedding of ionic III-V materials also apply to pulmonary exposure is unclear. While it has been demonstrated that micron-sized III-V particles, such as GaAs and InAs, are capable of inducing hazardous pulmonary effects in an occupational setting as well as in animal studies, the effect of submicron particles (e.g., the removal of asperities during processing of semiconductor wafers) is unclear. We used cytokine profiling to compare the pro-inflammatory effects of micron- and nanoscale GaAs and InAs particulates in cells as well as the murine lung 40 h and 21 days after oropharyngeal aspiration. Use of cytokine array technology in macrophage and epithelial cell cultures demonstrated a proportionally higher increase in the levels of matrix metalloproteinase inducer (EMMPRIN), macrophage migration inhibitory factor (MIF), and interleukin 1ß (IL-1ß) by nanosized (n) GaAs and n-InAs as well as As(III). n-GaAs and n-InAs also triggered higher neutrophil counts in the bronchoalveolar lavage fluid (BALF) of mice than micronscale particles 40 h post-aspiration, along with increased production of EMMPRIN and MIF. In contrast, in animals sacrificed 21 days after exposure, only n-InAs induced fibrotic lung changes as determined by increased lung collagen as well as increased levels of TGF-ß1 and PDGF-AA in the BALF. A similar trend was seen for EMMPRIN and matrix metallopeptidase (MMP-9) levels in the BALF. Nano- and micron-GaAs had negligible subacute effects. Importantly, the difference between the 40 h and 21 days data appears to be biopersistence of n-InAs, as demonstrated by ICP-OES analysis of lung tissue. Interestingly, an ionic form of In, InCl3, also showed pro-fibrogenic effects due to the formation of insoluble In(OH)3 nanostructures. All considered, these data indicate that while nanoscale particles exhibit increased pro-inflammatory effects in the lung, most effects are transient, except for n-InAs and insoluble InCl3 species that are biopersistent and trigger pro-fibrotic effects. These results are of potential importance for the understanding the occupational health effects of III-V particulates.

15.
Small ; 13(15)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28195425

RESUMO

Although numerous toxicological studies have been performed on carbon nanotubes (CNTs), a few studies have investigated their secondary and indirect effects beyond the primary target tissues/organs. Here, a cascade of events are investigated: the initiating event and the subsequent key events necessary for the development of phenotypes, namely CNT-induced pro-inflammatory effects on iron homeostasis and red blood cell formation, which are linked to anemia of inflammation (AI). A panel of CNTs are prepared including pristine multiwall CNTs (P-MWCNTs), aminated MWCNTs (MWCNTs-NH2 ), polyethylene glycol MWCNTs (MWCNTs-PEG), polyethyleneimine MWCNTs (MWCNTs-PEI), and carboxylated MWCNTs (MWCNTs-COOH). It has been demonstrated that all CNT materials provoke inflammatory cytokine interleukin-6 (IL-6) production and stimulate hepcidin induction, associated with disordered iron homeostasis, irrespective of exposure routes including intratracheal, intravenous, and intraperitoneal administration. Meanwhile, PEG and COOH modifications can ameliorate the activation of IL-6-hepcidin signaling. Long-term exposure of MWCNTs results in AI and extramedullary erythropoiesis. Thus, an adverse outcome pathway is identified: MWCNT exposure leads to inflammation, hepatic hepcidin induction, and disordered iron metabolism. Together, the combined data depict the hazardous secondary toxicity of CNTs in incurring anemia through inflammatory pathway. This study will also open a new avenue for future investigations on CNT-induced indirect and secondary adverse effects.

16.
ACS Nano ; 11(1): 501-515, 2017 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-28026936

RESUMO

The safe implementation of nanotechnology requires nanomaterial hazard assessment in accordance with the material physicochemical properties that trigger the injury response at the nano/bio interface. Since CuO nanoparticles (NPs) are widely used industrially and their dissolution properties play a major role in hazard potential, we hypothesized that tighter bonding of Cu to Fe by particle doping could constitute a safer-by-design approach through decreased dissolution. Accordingly, we designed a combinatorial library in which CuO was doped with 1-10% Fe in a flame spray pyrolysis reactor. The morphology and structural properties were determined by XRD, BET, Raman spectroscopy, HRTEM, EFTEM, and EELS, which demonstrated a significant reduction in the apical Cu-O bond length while simultaneously increasing the planar bond length (Jahn-Teller distortion). Hazard screening was performed in tissue culture cell lines and zebrafish embryos to discern the change in the hazardous effects of doped vs nondoped particles. This demonstrated that with increased levels of doping there was a progressive decrease in cytotoxicity in BEAS-2B and THP-1 cells, as well as an incremental decrease in the rate of hatching interference in zebrafish embryos. The dissolution profiles were determined and the surface reactions taking place in Holtfreter's solution were validated using cyclic voltammetry measurements to demonstrate that the Cu+/Cu2+ and Fe2+/Fe3+ redox species play a major role in the dissolution process of pure and Fe-doped CuO. Altogether, a safe-by-design strategy was implemented for the toxic CuO particles via Fe doping and has been demonstrated for their safe use in the environment.

17.
ACS Nano ; 10(12): 10966-10980, 2016 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-28024366

RESUMO

While the antibacterial properties of graphene oxide (GO) have been demonstrated across a spectrum of bacteria, the critical role of functional groups is unclear. To address this important issue, we utilized reduction and hydration methods to establish a GO library with different oxidation, hydroxyl, and carbon radical (•C) levels that can be used to study the impact on antibacterial activity. Using antibiotic-resistant bacteria as a test platform, we found that the •C density is most proximately associated with bacterial killing. Accordingly, hydrated GO (hGO), with the highest •C density, had the strongest antibacterial effects through membrane binding and induction of lipid peroxidation. To explore its potential applications, we demonstrated that coating of catheter and glass surfaces with hGO is capable of killing drug-resistant bacteria. In summary, •C is the principle surface moiety that can be utilized for clinical applications of GO-based antibacterial coatings.


Assuntos
Antibacterianos , Carbono , Grafite , Bactérias , Óxidos
18.
Sci Rep ; 6: 36490, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27819279

RESUMO

Blood plasma is the most popularly used sample matrix for metabolite profiling studies, which aim to achieve global metabolite profiling and biomarker discovery. However, most of the current studies on plasma metabolite profiling focused on either the polar metabolites or lipids. In this study, a comprehensive analysis approach based on HILIC-FTMS was developed to concurrently examine polar metabolites and lipids. The HILIC-FTMS method was developed using mixed standards of polar metabolites and lipids, the separation efficiency of which is better in HILIC mode than in C5 and C18 reversed phase (RP) chromatography. This method exhibits good reproducibility in retention times (CVs < 3.43%) and high mass accuracy (<3.5 ppm). In addition, we found MeOH/ACN/Acetone (1:1:1, v/v/v) as extraction cocktail could achieve desirable gathering of demanded extracts from plasma samples. We further integrated the MeOH/ACN/Acetone extraction with the HILIC-FTMS method for metabolite profiling and smoking-related biomarker discovery in human plasma samples. Heavy smokers could be successfully distinguished from non smokers by univariate and multivariate statistical analysis of the profiling data, and 62 biomarkers for cigarette smoke were found. These results indicate that our concurrent analysis approach could be potentially used for clinical biomarker discovery, metabolite-based diagnosis, etc.


Assuntos
Lipídeos/sangue , Plasma/química , Plasma/metabolismo , Adolescente , Adulto , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Espectrometria de Massas/métodos , Metabolômica/métodos , Reprodutibilidade dos Testes , Adulto Jovem
19.
Nanoscale ; 8(42): 18070-18086, 2016 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-27714147

RESUMO

Carbon nanotubes (CNTs) have promising applications in a wide range of biomedical fields, including imaging, drug/gene delivery and other therapeutics; however, the biosafety concerns of CNTs should be addressed. To date, many reports have documented the toxicological effects on the cells, tissue or organs that are in direct contact with the tubes; however, there is limited evidence to unravel the secondary toxicity upon CNT treatment. Moreover, more effort is needed to gain a definitive understanding of the adverse outcome pathway (AOP) for CNTs, and a pragmatic framework for risk assessment has not been established yet. In the current study, we aimed to decipher the secondary toxicity to joints under CNT exposure. We demonstrated that carboxylated multi-wall CNTs (MWCNTs-COOH) significantly provoked systemic pro-inflammatory responses, leading to synovial inflammation within knee joints, as evidenced by the infiltration of pro-inflammatory cells in the synovium and meniscus. Mechanistic studies showed that MWCNTs-COOH stimulated pro-inflammatory effects by activating macrophages, and the secreted pro-inflammatory cytokines primed the synoviocytes and chondrocytes, resulting in enhanced production of a large array of enzymes involved in articular cartilage degeneration, including matrix metalloproteinase (MMP) members and cyclooxygenase (COX) members, and increased enzymatic activity of MMPs was demonstrated. Blockade of the cytokines by antibodies significantly attenuated the production of these enzymes. Our current study thus suggests that there is a novel secondary toxicity of CNTs, namely a new AOP to understand the indirect effects of carbon nanotubes: synovial inflammation due to the alteration of the priming state of synoviocytes and chondrocytes under CNT-induced systemic inflammatory conditions.


Assuntos
Citocinas/imunologia , Inflamação/imunologia , Macrófagos/imunologia , Nanotubos de Carbono , Membrana Sinovial/citologia , Animais , Humanos , Ativação de Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Membrana Sinovial/imunologia , Células THP-1
20.
ACS Nano ; 10(8): 8054-66, 2016 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-27483033

RESUMO

Contrary to the notion that the use of fumed silica in consumer products can "generally (be) regarded as safe" (GRAS), the high surface reactivity of pyrogenic silica differs from other forms of synthetic amorphous silica (SAS), including the capacity to induce membrane damage and acute proinflammatory changes in the murine lung. In addition, the chain-like structure and reactive surface silanols also allow fumed silica to activate the NLRP3 inflammasome, leading to IL-1ß production. This pathway is known to be associated with subchronic inflammation and profibrogenic effects in the lung by α-quartz and carbon nanotubes. However, different from the latter materials, bolus dose instillation of 21 mg/kg fumed silica did not induce sustained IL-1ß production or subchronic pulmonary effects. In contrast, the NLRP3 inflammasome pathway was continuously activated by repetitive-dose administration of 3 × 7 mg/kg fumed silica, 1 week apart. We also found that while single-dose exposure failed to induce profibrotic effects in the lung, repetitive dosing can trigger increased collagen production, even at 3 × 3 mg/kg. The change between bolus and repetitive dosing was due to a change in lung clearance, with recurrent dosing leading to fumed silica biopersistence, sustained macrophage recruitment, and activation of the NLRP3 pathway. These subchronic proinflammatory effects disappeared when less surface-reactive titanium-doped fumed silica was used for recurrent administration. All considered, these data indicate that while fumed silica may be regarded as safe for some applications, we should reconsider the GRAS label during repetitive or chronic inhalation exposure conditions.


Assuntos
Inflamassomos , Pulmão/química , Nanotubos de Carbono , Dióxido de Silício/química , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA