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2.
Environ Microbiol Rep ; 12(2): 160-172, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31858707

RESUMO

Rhizomicrobiome, the communities of microorganisms surrounding the root of the plant, plays a vital role in promoting plant growth and health. The composition of rhizomicrobiome is dynamic both temporally and spatially, and is influenced greatly by the plant host and environmental factors. One of the key influencing factors is rhizodeposits, composed of root-released tissue cells, exudates, lysates, volatile compounds, etc. Rhizodeposits are rich in carbon and nitrogen elements, and able to select and fuel the growth of rhizomicrobiome. In this minireview, we overview the generation, composition and dynamics of rhizodeposits, and discuss recent work describing the general and specific impacts of rhizodeposits on rhizomicrobiome. We focus further on root exudates, the most dynamic component of rhizodeposits, and review recent progresses about the influence of specific root exudates in promoting bacterial root colonization, inducing biofilm development, acting as plant defence and shaping the rhizomicrobiome.

3.
J Cancer ; 10(27): 6915-6924, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839827

RESUMO

Objective: Since the introduction in 2004, global usage of e-cigarettes (ECs) has risen exponentially. However, the risks of ECs on oral health are uncertain. The purpose of this study is to understand if EC aerosol exposure impacts the gene pathways of normal human oral keratinocytes (NHOKs), particularly the unfolded protein response (UPR) pathway. Materials and methods: EC aerosols were generated reproducibly with a home-made puffing device and impinged into the culture medium for NHOKs. DNA microarrays were used to profile the gene expression changes in NHOKs treated with EC aerosols, and the Ingenuity Pathway Analysis (IPA) was used to reveal signaling pathways altered by the EC aerosols. Quantitative PCR was used to validate the expression changes of significantly altered genes. Results: DNA microarray profiling followed by IPA revealed a number of signaling pathways, such as UPR, cell cycle regulation, TGF-ß signaling, NRF2-mediated oxidative stress response, PI3K/AKT signaling, NF-κB signaling, and HGF signaling, activated by EC aerosols in NHOKs. The UPR pathway genes, C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), X box binding protein 1 (XBP1), and inositol-requiring enzyme 1 alpha (IRE1α) were all significantly up-regulated in EC aerosol-treated NHOKs whereas immunoglobulin heavy-chain binding protein (BIP) and PRKR-like ER kinase (PERK) were slightly up-regulated. qPCR analysis results were found to be well correlated with those from the DNA microarray analysis. The most significantly changed genes in EC aerosol-treated NHOKs versus untreated NHOKs were CHOP, ATF4, XBP1, IRE1α and BIP. Meanwhile, Western blot analysis confirmed that CHOP, GRP78 (BIP), ATF4, IRE1α and XBP1s (spliced XBP1) were significantly up-regulated in NHOKs treated with EC aerosols. Conclusion: Our results indicate that EC aerosols up-regulate the UPR pathway genes in NHOKs, and the induction of UPR response is mediated by the PERK - EIF2α - ATF4 and IRE1α - XBP1 pathways.

4.
ACS Nano ; 13(11): 13065-13082, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31682760

RESUMO

The widespread use of metal oxide nanoparticles (MOx NPs) poses a risk of exposure that may lead to adverse health effects on humans. Even though a number of toxicological methodologies are available for assessing nanotoxicity, the effect of MOx NPs on cell metabolism in vitro and in vivo remains largely unknown, especially under the exposure to low-dose or supposedly low-toxicity MOx NPs. In this study, liquid chromatography-mass spectrometry (LC-MS) based metabolomics was used to reveal significantly altered metabolites and metabolic pathways in human bronchial epithelial cells exposed to four different types of MOx NPs (ZnO, SiO2, TiO2, and CeO2) at both high (25 µg/mL) and low (12.5 µg/mL) doses. We demonstrated that high-dose ZnO NPs caused severe cytotoxicity with altered metabolism of amino acids, nucleotides, nucleosides, tricarboxylic acid cycle, lipids, inflammation/redox, and fatty acid oxidation, as well as the elevation of toxic and DNA damage related metabolites. Fewer metabolomic alterations were induced by low-dose ZnO NPs. However, most metabolites significantly altered by high-dose ZnO NPs were also slightly changed by low-dose ZnO NPs. On the other hand, the cells exposed to SiO2, TiO2, and CeO2 NPs at either high or low dose displayed low cytotoxicity with similar metabolomic alterations, although each type of NPs induced distinct changes of certain metabolites. These three NPs significantly affected the metabolic pathways of sphingosine-1-phosphate, fatty acid oxidation, folate cycle, inflammation/redox, and lipid metabolism. In addition, dose-dependent effects were observed for a number of metabolites significantly altered by respective MOx NPs. Representative metabolites of the significantly altered metabolic pathways were successfully validated in vitro using enzymatic assays. More importantly, these representative metabolites were further validated in a mouse model after lung exposure to respective NPs, indicating that in vitro metabolomic findings may be used to effectively predict the toxicological effects in vivo. Despite functional assay results demonstrating that the changes in cellular functions were largely reflected by the metabolomic alterations, LC-MS-based metabolomics was sensitive enough to detect the subtle metabolomic changes when functional cellular assays showed no significant difference. Collectively, our studies have unveiled potential metabolic mechanisms of MOx NP-induced nanotoxicity in lung epithelial cells and demonstrated the sensitivity and feasibility of using metabolomic signatures to understand and predict nanotoxicity in vivo.

5.
Langmuir ; 35(45): 14688-14695, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31635450

RESUMO

Physicochemical properties of nanomaterials play important roles in determining their toxicological profiles during nano-biointeraction. Among them, surface modification is one of the most effective manners to tune the cytotoxicity induced by nanomaterials. However, currently, there is no consistency in surface modification including moiety types and quantities considering the conflicting toxicological profiles of particles across different studies. In this study, in order to systematically investigate how the moiety density affects cytotoxicity of NPs, we chose three different types of functional groups, that is, -NH2, -COOH, and -PEG, and further controlled their densities on modified Stöber silica nanoparticles (NPs). We demonstrated that densities of functional groups could significantly affect the cytotoxicities of Stöber silica NPs. Regardless of the types of functional groups, high grafting densities could ameliorate the cytotoxicities induced by Stöber silica NPs in macrophages, for example, J774A.1 and N9 cells. When equal amounts of functional groups were present, the cell viability increased in the order of -COOH < -NH2 < -PEG. Furthermore, it was shown that surface modification could significantly affect the quantities of the surface silanol, which is the determining factor that affects their cytotoxicity. These results show that it is critical to control the surface moiety both quantitatively and qualitatively, which can tune the interaction outcomes at the nano-bio interface. The results found in this article provide useful guidance to adjust nanomaterial cytotoxicity for safer biomedical applications.

6.
Org Lett ; 21(21): 8582-8586, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618034

RESUMO

A chiral N-heterocyclic-carbene-catalyzed cascade asymmetric desymmetrization reaction of cyclopentenediones with enals has been successfully initiated, followed with tandem aldol annulation, aromatization, as well as sequential methylation. The reactions proceeded well under mild reaction conditions, with broad substrate scope and good functional group tolerance, providing a rapid access to highly functionalized chiral 2,2-disubstituted 1,3-indandione derivatives containing an all-carbon quaternary stereogenic center in moderate to good yields with high enantioselectivities.

7.
Nanoscale ; 11(27): 12965-12972, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31259344

RESUMO

With the wide application of Stöber silica nanoparticles and their ability to access the brain, it is crucial to evaluate their neurotoxicity. In this study, we used three in vitro model cells, i.e., N9, bEnd.3 and HT22 cells, representing microglia, microendothelial cells and neurons, respectively, to assess the neurotoxicity of Stöber silica nanoparticles with different sizes. We found that Stöber silica nanoparticles almost had no effect on the viability of bEnd.3 and HT22 cells. In contrast, they induced size-dependent toxicity in N9 cells, which represent the residential macrophages of the central nervous system. Further mechanistic study demonstrated that the toxicity in N9 cells was related to their surface silanol display. In addition, we demonstrated that Stöber silica nanoparticles induced the production of mitochondrial ROS, release of IL-1ß, cleavage of GSDMD, and occurrence of pyroptosis in N9 cells. Features of pyroptosis were also observed in primary microglia and macrophage J774A.1. In conclusion, these findings were helpful for the safety consideration of Stöber silica nanoparticles considering their wide applications in our daily life.


Assuntos
Microglia/metabolismo , Mitocôndrias/metabolismo , Nanopartículas/efeitos adversos , Piroptose/efeitos dos fármacos , Dióxido de Silício/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Microglia/patologia , Mitocôndrias/patologia , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Dióxido de Silício/farmacologia
8.
Int J Nanomedicine ; 14: 4167-4186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239675

RESUMO

Engineered nanomaterials (ENMs) have been widely used in various fields due to their novel physicochemical properties. However, the use of ENMs has led to an increased exposure in humans, and the safety of ENMs has attracted much attention. It is universally acknowledged that ENMs could enter the human body via different routes, eg, inhalation, skin contact, and intravenous injection. Studies have proven that ENMs can cross or bypass the blood-brain barrier and then access the central nervous system and cause neurotoxicity. Until now, diverse in vivo and in vitro models have been developed to evaluate the neurotoxicity of ENMs, and oxidative stress, inflammation, DNA damage, and cell death have been identified as being involved. However, due to various physicochemical properties of ENMs and diverse study models in existing studies, it remains challenging to establish the structure-activity relationship of nanomaterials in neurotoxicity. In this paper, we aimed to review current studies on ENM-induced neurotoxicity, with an emphasis on the molecular and cellular mechanisms involved. We hope to provide a rational material design strategy for ENMs when they are applied in biomedical or other engineering applications.


Assuntos
Nanoestruturas/toxicidade , Nanotecnologia , Neurotoxinas/toxicidade , Morte Celular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Dano ao DNA , Humanos , Nanoestruturas/química
9.
Chem Soc Rev ; 48(16): 4387-4400, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31237282

RESUMO

Bioinspired nanostructures can be the ideal functional smart materials to bridge the fundamental biology, biomedicine and nanobiotechnology fields. Among them, short peptides are among the most preferred building blocks as they can self-assemble to form versatile supramolecular architectures displaying unique physical and chemical properties, including intriguing optical features. Herein, we discuss the progress made over the past few decades in the design and characterization of optical short peptide nanomaterials, focusing on their intrinsic photoluminescent and waveguiding performances, along with the diverse modulation strategies. We review the complicated optical properties and the advanced applications of photoactive short peptide self-assemblies, including photocatalysis, as well as photothermal and photodynamic therapy. The diverse advantages of photoactive short peptide self-assemblies, such as eco-friendliness, morphological and functional flexibility, and ease of preparation and modification, endow them with the capability to potentially serve as next-generation, bio-organic optical materials, allowing the bridging of the optics world and the nanobiotechnology field.


Assuntos
Nanoestruturas/química , Peptídeos/química , Catálise , Glucose/análise , Humanos , Hidrogéis/química , Luz , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Porfirinas/química , Porfirinas/uso terapêutico
10.
Nano Lett ; 19(7): 4478-4489, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31244230

RESUMO

Silver nanoparticles (Ag NPs) have promising plasmonic properties, however, they are rarely used in biomedical applications because of their potent toxicity. Herein, an electron compensation effect from Au to Ag was applied to design safe Au@Ag core-shell NPs. The Ag shell thickness was precisely regulated to enable the most efficient electron enrichment in Ag shell of Au@Ag2.4 NPs, preventing Ag oxidation and subsequent Ag+ ion release. X-ray photoelectron spectroscopy and X-ray absorption near-edge structure analysis revealed the electron transfer process from Au core to Ag shell, and inductively coupled plasma optical emission spectroscopy analysis confirmed the low Ag+ ion release from Au@Ag2.4 NPs. Bare Au@Ag2.4 NPs showed much lower toxicological responses than Ag NPs in BEAS-2B and Raw 264.7 cells and acute lung inflammation mouse models, and PEGylation of Au@Ag2.4 NPs could further improve their safety to L02 and HEK293T cells as well as mice through intravenous injection. Further, diethylthiatri carbocyanine iodide attached pAu@Ag2.4 NPs exhibited intense surface-enhanced Raman scattering signals and were used for Raman imaging of MCF7 cells and Raman biosensing in MCF7 tumor-bearing mice. This electron compensation effect opens up new opportunity for broadening biomedical application of Ag-based NPs.

11.
Vaccine ; 37(24): 3167-3178, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31047671

RESUMO

In conjugate, inactivated, recombinant, and toxoid vaccines, adjuvants are extensively and essentially used for enhanced and long-lasting protective immune responses. Depending on the type of diseases and immune responses required, adjuvants with different design strategies are developed. With aluminum salt-based adjuvants as the most used ones in commercial vaccines, other limited adjuvants, e.g., AS01, AS03, AS04, CpG ODN, and MF59, are used in FDA-approved vaccines for human use. In this paper, we review the uses of different adjuvants in vaccines including the ones used in FDA-approved vaccines and vaccines under clinical investigations. We discuss how adjuvants with different formulations could affect the magnitude and quality of adaptive immune response for optimized protection against specific pathogens. We emphasize the molecular mechanisms of various adjuvants, with the aim to establish structure-activity relationships (SARs) for designing more effective and safer adjuvants for both preventative and therapeutic vaccines.

12.
Water Res ; 151: 215-225, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30597444

RESUMO

Microplastics (<5 mm) are increasingly detected in aquatic environment, and the high levels of brominated flame retardants (BFRs) contained in them can potentially impact water quality. This study characterized the release kinetics of polybrominated diphenyl ethers (PBDEs) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) from millimeter-sized microplastic pellets in water at environmentally relevant temperatures. Leaching rates of BFRs from the microplastic pellets made of acrylonitrile butadiene styrene (ABS) were found to be controlled by their diffusion within the plastic matrix, and their diffusion coefficients (D) in the plastic matrices ranged from 10-28.30 to 10-20.84 m2 s-1. The apparent activation energies of the BFRs' diffusion coefficients were estimated to be in the range of 64.1-131.8 kJ mol-1 based on their temperature dependence and the Arrhenius equation. The diffusion coefficients of the BFRs decrease with their molecular diameters, while the activation energies for diffusion increase with the molecular diameters, which are indicative of significant steric hindrance for BFR diffusion within the plastic matrices. A semi-empirical linear relationship was observed between Log10D and the glass transition temperature (Tg) of plastics, which allows prediction of the diffusion coefficients of BFRs in other types of microplastics commonly found in marine environment. The half-lives of BFR leaching (i.e., 50% depletion) from the microplastic pellets would range from tens of thousands to hundreds of billions of years at ambient temperatures if their physical and chemical structures could remain intact. Although the release fluxes of BFRs from microplastics are extremely low under the model conditions, a range of physical and chemical processes in the natural environment and the digestive systems of organisms that ingested them could potentially accelerate their leaching by causing breakdown and swelling of the plastic matrices.


Assuntos
Retardadores de Chama , Hidrocarbonetos Bromados , Difusão , Éteres Difenil Halogenados , Cinética , Plásticos
13.
Angew Chem Int Ed Engl ; 58(3): 796-800, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30474178

RESUMO

Prototypes of natural biosystems provide opportunities for artificial biomimetic systems to break the limits of natural reactions and achieve output control. However, mimicking unique natural structures and ingenious functions remains a challenge. Now, multiple biochemical reactions were integrated into artificially designed compartments via molecular assembly. First, multicompartmental silica nanoparticles with hierarchical structures that mimic the chloroplasts were obtained by a templated synthesis. Then, photoacid generators and ATPase-liposomes were assembled inside and outside of silica compartments, respectively. Upon light illumination, protons produced by a photoacid generator in the confined space can drive the liposome-embedded enzyme ATPase towards ATP synthesis, which mimics the photophosphorylation process in vitro. The method enables fabrication of bioinspired nanoreactors for photobiocatalysis and provides insight for understanding sophisticated biochemical reactions.

14.
Angew Chem Int Ed Engl ; 58(4): 1110-1114, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30517771

RESUMO

A proton gradient across a lipid membrane is required for the production of biochemical fuel. Much effort has been devoted to reactions involving proton production in biomimetic assembled architectures under mild conditions. Herein, we explored thiol-based self-assembled monolayer chemistry on a naked gold surface for the production of biochemical fuel. Protons are generated when alkanethiols self-assemble on a gold surface, and the proton yield can be tuned by the choice of thiol and by variation of the procedure used for the deposition of gold. Consequently, the proton gradient across a lipid membrane above the gold surface can be modulated to vary the production rate of biochemical fuel performed by lipid-embedded motor proteins. Our work presents evidence that a simple and efficient abiotic chemical reaction in a well-defined biohybrid system can convert unnatural chemicals, namely alkanethiols, into bioenergy molecules, a finding that has a great potential in biofuel-driven catalysis and devices.

15.
ACS Appl Mater Interfaces ; 11(1): 31-36, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30574778

RESUMO

Herein, we report on the unidirectional branched assembly of diphenylalanine dipeptide through a one-step rapid evaporation process. Large numbers of crystalline tubular branches with smooth surfaces are developed from a hexagonal solid microrod mimicking a "Christmas tree". Density functional theory suggests the formation of tubular diphenylalanine aggregates with cis isomers. The diphenylalanine branched assembly shows good optical waveguide properties that can transmit light homogeneously along the crystal fibers as well as harvest light from the tips of branches to the microrod terminals. These findings hold importance in the development of bioinspired optical fibers for information transmission in a microscale.

16.
J Chromatogr A ; 1570: 1-9, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30153981

RESUMO

This article reported a new strategy for resin activation with divinyl sulfone using catalytic oxa-Michael addition in a controllable manner. By screening a variety of organocatalysts, PPh3 and DMAP stand out with high catalytic efficiency in aprotic solutions. X-ray photoelectron spectroscopy (XPS) analysis indicates high reaction efficiency and less side reactions than traditional aqueous reactions, resulting in high activation density. A maximum activation density of 157.5 ±â€¯1.2 µmol/g resin was achieved in 12 h using PPh3 as catalyst, which is 1.5 times higher than the traditional aqueous reactions. Followed by conjugation with a chromatographic ligand, i.e., 4-mercaptoethyl pyridine (MEP), the resin is capable of antibody purification. Using IgG and BSA as model proteins, adsorption isotherms and dynamic binding behavior of the resin samples were investigated. A higher affinity and dynamic binding capacity of IgG was observed on resins with higher ligand density. Finally, the resin samples were applied to the purification of a therapeutic monoclonal antibody from cell culture supernatant. The recovery of the resin samples with high ligand density are 70% higher than those of the commercial resin (MEP HyperCel). Moreover, our method achieves a controllable chromatographic ligand density by varying reaction times, which is useful to clarify the density-affinity relationship and improve process-scale antibody purification.


Assuntos
Antiasmáticos/isolamento & purificação , Cromatografia de Afinidade/métodos , Omalizumab/isolamento & purificação , Piridinas/química , Resinas Vegetais/química , Sulfonas/química , Adsorção , Animais , Células CHO , Catálise , Cricetulus , Ligantes
17.
Biotechnol J ; 13(9): e1700588, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30039929

RESUMO

Mycobacterium smegmatis is an important model strain of Mycobacterium for scientific study because it is non-pathogenic and grows rapidly. However, research is limited by the low efficiency and time-consuming nature of existing genome editing tools. Although the Streptococcus pyogenes CRISPR-Cas9 system is widely used in bacterial genome editing, it cannot be introduced into M. smegmatis because of its toxicity. The authors test 14 different Cas effector proteins in M. smegmatis. Cas9 (TdCas9_m) from Treponema denticola, Cas9 (NmCas9) from Neisseria meningitidis, and Corynebacterium glutamicum codon-optimized Cpf1 (FnCpf1_cg) from Francisella tularensis do not affect cell growth. The numbers of transformant plasmids expressing TdCas9_m, NmCas9, or FnCpf1_cg, and guide RNAs (gRNA) targeting ku(MSMEG_5580), ligD(MSMEG_6301), pta(MSMEG_0783), or ackA(MSMEG_0784) decreases by about 10-, 10-, or 100-fold, respectively, compared with plasmids expressing only the Cas effector proteins. Non-homologous end joining (NHEJ) is detected only in the CRISPR-FnCpf1_cg system. The one-plasmid-based, CRISPR-FnCpf1-assisted NHEJ system enables N iterative rounds of genome editing in 7N + 2 days, with an editing efficiency up to 70%; thus, this system should greatly reduce the necessary genome manipulation time for M. smegmatis.


Assuntos
Reparo do DNA por Junção de Extremidades , Edição de Genes/métodos , Mycobacterium smegmatis/genética , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Corynebacterium glutamicum/genética , Genoma Bacteriano
18.
Adv Healthc Mater ; 7(12): e1701357, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29688635

RESUMO

Photodynamic therapy (PDT) still faces two main problems on cancer therapy. One is how to improve PDT efficiency against hypoxic environment of tumors. The other one is how to overcome the limit of short wavelength light to increase PDT treatment depth. In this work, an intraparticle fluorescence resonance energy transfer (FRET) platform is designed to address these problems together. The nanoparticles are doped with multicomponents, such as catalase, two-photon dyes, and traditional photosensitizers, with a simple "one-pot" and green method. On the one hand, catalase can catalyze intracellular H2 O2 into O2 and promote PDT efficiency. One the other hand, photosensitizers can be excited indirectly by two-photon lasers through an intraparticle FRET mechanism, which results in deeper tissue penetration for PDT. These properties are verified through the material induced cytotoxicity in light or in dark and in vivo blocking blood-vessel experiment.


Assuntos
Transferência Ressonante de Energia de Fluorescência/métodos , Nanopartículas , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Linhagem Celular Tumoral , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia
19.
ACS Nano ; 12(4): 3836-3852, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29543433

RESUMO

The liver and the mononuclear phagocyte system are a frequent target for engineered nanomaterials, either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. We not only observed differences between KCs and hepatocytes, but also differences in the toxicological profiles of transition-metal oxides (TMOs, e. g., Co3O4) versus rare-earth oxide (REO) NPs ( e. g., Gd2O3). While pro-oxidative TMOs induced the activation of caspases 3 and 7, resulting in apoptotic cell death in both cell types, REOs induced lysosomal damage, NLRP3 inflammasome activation, caspase 1 activation, and pyroptosis in KCs. Pyroptosis was accompanied by cell swelling, membrane blebbing, IL-1ß release, and increased membrane permeability, which could be reversed by knockdown of the pore forming protein, gasdermin D. Though similar features were not seen in hepatocytes, the investigation of the cytotoxic effects of REO NPs could also be seen to affect macrophage cell lines such as J774A.1 and RAW 264.7 cells as well as bone marrow-derived macrophages. These phagocytic cell types also demonstrated features of pyroptosis and increased IL-1ß production. Collectively, these findings demonstrate important mechanistic considerations that can be used for safety evaluation of metal oxides, including commercial products that are developed from these materials.


Assuntos
Apoptose/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas/química , Óxidos/farmacologia , Elementos de Transição/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/metabolismo , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxidos/química , Células RAW 264.7 , Elementos de Transição/química
20.
Talanta ; 182: 600-605, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29501199

RESUMO

Alanine aminotransferase (ALT) plays significant role in biological and clinical research. In this study, a unique ALT enzyme reactor based on multifunctional polymer@magnetic nanoparticles has been constructed for the first time and the enzymolysis efficiency has been evaluated by chiral ligand exchange capillary electrophoresis technique. Poly(N-acryloxysuccinimide) has been synthesized by reversible addition-fragmentation chain transfer polymerization method and immobilized on the magnetic nanoparticles via the succinimide group in the polymer. Interestingly, the enzyme also could easily react with the succinimide group, which enables of ALT covalent bonding onto the polymer. The enzyme amount immobilized and the immobilization time have been investigated. Comparing with free ALT in solution (Vmax of free enzyme = 0.6 mM min-1), the resultant enzyme reactor has exhibited good reusability and stability, and displayed about five times enhanced enzymolysis efficiency with L-alanine as the substrate (Vmax of enzyme reactor = 3.4 mM min-1). Furthermore, the prepared enzyme reactor has been applied in ALT inhibitors screening. The enzyme reactors based on the multifunctional polymer@magnetic nanoparticles have depicted great potential in anti-liver drugs development, liver diseases study and ALT related biological process inspect.


Assuntos
Alanina Transaminase/química , Alanina/química , Reatores Biológicos , Enzimas Imobilizadas/química , Nanopartículas de Magnetita/química , Acrilatos/química , Alanina Transaminase/antagonistas & inibidores , Biocatálise , Eletroforese Capilar/métodos , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Enzimas Imobilizadas/antagonistas & inibidores , Reutilização de Equipamento , Ensaios de Triagem em Larga Escala , Humanos , Cinética , Nanopartículas de Magnetita/ultraestrutura , Polimerização , Succinimidas/química
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