RESUMEN
Endocrine disruptors such as bisphenol A (BPA) adversely affect the environment and human health. Laccases are used for the efficient biodegradation of various persistent organic pollutants in an environmentally safe manner. However, the direct application of free laccases is generally hindered by short enzyme lifetimes, non-reusability, and the high cost of a single use. In this study, laccases were immobilized on a novel magnetic three-dimensional poly(ethylene glycol) diacrylate (PEGDA)-chitosan (CS) inverse opal hydrogel (LAC@MPEGDA@CS@IOH). The immobilized laccase showed significant improvement in the BPA degradation performance and superior storage stability compared with the free laccase. 91.1% of 100 mg/L BPA was removed by the LAC@MPEGDA@CS@IOH in 3 hr, whereas only 50.6% of BPA was removed by the same amount of the free laccase. Compared with the laccase, the outstanding BPA degradation efficiency of the LAC@MPEGDA@CS@IOH was maintained over a wider range of pH values and temperatures. Moreover, its relative activity of was maintained at 70.4% after 10 cycles, and the system performed well in actual water matrices. This efficient method for preparing immobilized laccases is simple and green, and it can be used to further develop ecofriendly biocatalysts to remove organic pollutants from wastewater.
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Compuestos de Bencidrilo , Enzimas Inmovilizadas , Lacasa , Fenoles , Polietilenglicoles , Contaminantes Químicos del Agua , Lacasa/química , Lacasa/metabolismo , Fenoles/química , Contaminantes Químicos del Agua/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Polietilenglicoles/química , Quitosano/química , Hidrogeles/química , Biodegradación Ambiental , Disruptores Endocrinos/químicaRESUMEN
Cuproptosis, dependent on Cu overload, presents novel opportunities for cancer therapy. Cu-based nanomaterials have shown excellent advantages for the intracellular delivery of Cu. However, the biological process of Cu nanomaterials transporting Cu ions into cancer cells remains unclear. In this study, we tracked the Cu ion release process of copper nanowires (CuNWs) and copper nanoparticles (CuNPs) at the single-cell level. CuNWs with 5-µm length and CuNPs were found to be completely internalized by cancer cells. Interestingly, CuNWs escaped from the endolysosomal system, whereas CuNPs were mainly trapped in the lysosomes. This specific intracellular distribution of CuNWs led to cytoplasmic Cu ion overload, directly damaging mitochondria and inducing dihydrolipoamide S-acetyltransferase (DLAT) protein aggregation. Through these excessive Cu ions, CuNWs triggered more efficient cuproptosis than CuNPs to further increase cell death. Thus, CuNWs are more effective in delivering Cu ions than CuNPs, providing a novel perspective for designing cuproptosis-based functional nanomaterials for cancer therapy.
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The response sensitivity to toxic substances is the most concerned performance of animal model in chemical risk assessment. Casper (mitfaw2/w2;mpv17a9/a9), a transparent zebrafish mutant, is a useful in vivo model for toxicological assessment. However, the ability of casper to respond to the toxicity of exogenous chemicals is unknown. In this study, zebrafish embryos were exposed to five environmental chemicals, chlorpyrifos, lindane, α-endosulfan, bisphenol A, tetrabromobisphenol A (TBBPA), and an antiepileptic drug valproic acid. The half-lethal concentration (LC50) values of these chemicals in casper embryos were 62-87 % of that in the wild-type. After TBBPA exposure, the occurrence of developmental defects in the posterior blood island of casper embryos was increased by 67-77 % in relative to the wild-type, and the half-maximal effective concentration (EC50) in casper was 73 % of that in the wild-type. Moreover, the casper genetic background significantly increased the hyperlocomotion caused by chlorpyrifos and lindane exposure compared with the wild-type. These results demonstrated that casper had greater susceptibility to toxicity than wild-type zebrafish in acute toxicity, developmental toxicity and neurobehavioral toxicity assessments. Our data will inform future toxicological studies in casper and accelerate the development of efficient approaches and strategies for toxicity assessment via the use of casper.
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Pez Cebra , Animales , Embrión no Mamífero/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Cloropirifos/toxicidad , Pruebas de Toxicidad , Bifenilos Polibrominados/toxicidadRESUMEN
There is growing concern about the distribution of nanoplastics (NPs) in the central nervous system (CNS), whereas intrusion is poorly understood. In this study, fluorescent-labeled polystyrene NPs (PS-NPs) were microinjected into different areas of zebrafish embryo to mimic different routes of exposure. PS-NPs were observed in the brain, eyes, and spinal cord through gametal exposure. It indicated that maternally derived PS-NPs were specially distributed in the CNS of zebrafish during early development. Importantly, these NPs were stranded in the CNS but not transferred to other organs during development. Furthermore, using neuron GFP-labeled transgenic zebrafish, colocalization between NPs and the neuron cells revealed that NPs were mostly enriched in the CNS surrounded but not the neurons. Even so, the intrusion of NPs into the CNS induced the significant upregulation of some neurotransmitter receptors, leading to an inhibited effect on the movement of zebrafish larvae. This work provides insights into understanding the intrusion and distribution of NPs in the CNS and the subsequent potential adverse effects.
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Sistema Nervioso Central , Poliestirenos , Pez Cebra , Animales , Pez Cebra/embriología , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/efectos de los fármacos , Poliestirenos/química , Nanopartículas/química , Nanopartículas/metabolismo , Animales Modificados Genéticamente , Microplásticos/toxicidadRESUMEN
Halobenzoquinones (HBQs), an emerging unregulated category of disinfection byproduct (DBP) in drinking water, have aroused an increasing concern over their potential health risks. However, the chronic toxicity of HBQs at environmentally relevant concentrations remains largely unknown. Here, the occurrence and concentrations of 13 HBQs in drinking water from a northern megacity in China were examined using ultrahigh performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-MS/MS). Four HBQs, including 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), 2,3,6-trichloro-1,4-benzoquinone (TriCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ), were detected beyond 50% occurrence frequency and at median concentrations from 4 to 50 ng/L. The chronic toxicity of these four HBQs to normal human colon and liver cells (FHC and THLE-2) was investigated at these concentrations. After 90 days of exposure, 2,5-DBBQ and 2,6-DCBQ induced the highest levels of oxidative stress and deoxyribonucleic acid (DNA) damage in colon and liver cells, respectively. Moreover, 2,5-DBBQ and 2,6-DCBQ were also found to induce epithelial-mesenchymal transition (EMT) in normal human liver cells via the extracellular signal regulated kinase (ERK) signaling pathway. Importantly, heating to 100 °C (boiling) was found to efficiently reduce the levels of these four HBQs in drinking water. These results suggested that environmentally relevant concentrations of HBQs could induce cytotoxicity and genotoxicity in normal human cells, and boiling is a highly efficient way of detoxification for HBQs.
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Benzoquinonas , Agua Potable , Contaminantes Químicos del Agua , Agua Potable/química , Humanos , Benzoquinonas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Espectrometría de Masas en Tándem , ChinaRESUMEN
Recently intensified oil exploitation has resulted in the discharge of large amounts of wastewater containing high concentrations of organic matter and nutrients into the receiving aquatic and soil environments; however, the effects of oilfield-produced water on the soil microbiota are poorly understood. In this study, we conducted a comprehensive analysis to reveal the composition and diversity of the microbial community at horizontal and vertical scales in a typical arid soil receiving oilfield-produced water in Northwest China. Oilfield-produced water caused an increase in microbial diversity at the horizontal scale, and the communities in the topsoil were more variable than those in the subsoil. Additionally, the microbial taxonomic composition differed significantly between the near- and far-producing water soils, with Proteobacteria and Halobacterota dominating the water-affected and reference soil communities, respectively. Soil property analysis revealed that pH, salt, and total organic content influenced the bacterial communities. Furthermore, the oil-produced water promoted the complexity and modularity of distance-associated microbial networks, indicating positive interactions for soil ecosystem function, but not for irrigation or livestock watering. This is the first detailed examination of the microbial communities in soil receiving oilfield-produced water, providing new insights for understanding the microbial spatial distributions in receiving arid soils.
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Microbiota , Suelo , Suelo/química , Agua , Yacimiento de Petróleo y Gas , Bacterias , Microbiología del SueloRESUMEN
Microplastics (MPs) are ubiquitous in environmental compartments and consumer products. Although liver is frequently reported to be a target organ of MP accumulation in mammals, few studies have focused on MP hepatoxicity in humans. In this study, we used normal human liver cells, THLE-2, to assess the acute and chronic toxicity of polystyrene (PS) MPs with sizes of 0.1 and 1 µm. The results showed that after 48 h of exposure, both kinds of PS MPs could enter THLE-2 cells and cause no obviously acute cytotoxicity at <20 µg/mL. In contrast, metabolomic analysis revealed that 90 days of PS MPs exposure at environmentally relevant dose (0.2 µg/mL) could significantly alter the metabolic profiles of the cells, especially the nanosized MPs. KEGG pathway analysis showed that the ATP-binding cassette (ABC) transporter pathway was the most significantly changed pathway. Cell functional tests confirmed that chronic PS MP treatment could inhibit the activity of the ABC efflux transporter and further increase the cytotoxicity of arsenic, indicating that the PS MPs had a chemosensitizing effect. These findings underline the chronic risk of MPs to human liver.
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Poliestirenos , Contaminantes Químicos del Agua , Animales , Humanos , Poliestirenos/toxicidad , Poliestirenos/metabolismo , Microplásticos/toxicidad , Microplásticos/metabolismo , Plásticos/toxicidad , Transportadoras de Casetes de Unión a ATP , Hígado/metabolismo , Contaminantes Químicos del Agua/toxicidad , Mamíferos/metabolismoRESUMEN
Bisphenol A (BPA) and its analogs are endocrine-disrupting chemicals that are frequently detected in environmental and human samples. However, the effective removal of BPA and its analogs has not yet been extensively studied. Herein, we introduce a novel enzyme reactor for the degradation of BPA and its analogs in water. The influence of pore size on the degradation efficiency of immobilized laccase in the spatial nanopores of hydrogel was investigated using BPA as a representative compound. This showed that nanopores enhance the activity of immobilized laccases in a pore size-dependent manner and increase their stability. Compared with the same amount of free laccase, the 50 mg/L BPA degradation performance of laccase immobilized in 76 nm nanopores increased to 300 %. Taking advantage of magnetic separation, this immobilized laccase can be reused, and its degradation capacity was maintained at over 73.7 % after ten reactions. Moreover, the degradation of seven BPA analogs was 1.03-5.88 times higher using laccase immobilized in nanopores compared with free laccase. Also, the biocatalyst could efficiently degrade BPA analogs in real water matrix. This study opens up a new avenue for the removal of BPA and its analogs by immobilizing laccase in nanopores, overcoming the key limitations introduced by the short enzyme life span and non-reusability.
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Surface modifications are generally used to functionalize QDots to improve their properties for practical applications, but the relationship between QDot modification and biological activity is not well understood. Using an early staged zebrafish model, we investigated the biodistribution and toxicity of CdSe/ZnS QDots with four types of modifications, including anionic poly(ethylene glycol)-carboxyl ((PEG)n-COOH), anionic mercaptopropionic acid (MPA), zwitterionic glutathione (GSH), and cationic cysteamine (CA). None of the QDots showed obvious toxicity to zebrafish embryos prior to hatching because the zebrafish chorion is an effective barrier that protects against QDot exposure. The QDots were mainly absorbed on the epidermis of the target organs after hatching and were primarily deposited in the mouth and gastrointestinal tract when the zebrafish started feeding. CA-QDots possessed the highest adsorption capacity; however, (PEG)n-COOH-QDots showed the most severe toxicity to zebrafish, as determined by mortality, hatching rate, heartbeat, and malformation assessments. It shows that the toxicity of the QDots is mainly attributed to ROS generation rather than Cd2+ release. This study provides a comprehensive understanding of the environmental and ecological risks of nanoparticles in relation to their surface modification.
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Nanopartículas , Puntos Cuánticos , Animales , Puntos Cuánticos/toxicidad , Pez Cebra , Distribución Tisular , PolietilenglicolesRESUMEN
It is challenging to achieve high selectivity over Pt-metal-oxide catalysts widely used in many selective oxidation reactions because Pt is prone to over-oxidize substrates. Herein, our sound strategy for enhancing the selectivity is to saturate the under-coordinated single Pt atoms with Cl- ligands. In this system, the weak electronic metal-support interactions between Pt atoms and reduced TiO2 cause electron extraction from Pt to Cl- ligands, resulting in strong Pt-Cl bonds. Therefore, the two-coordinate single Pt atoms adopt a four-coordinate configuration and thus inactivated, thereby inhibiting the over-oxidation of toluene over Pt sites. The selectivity for the primary C-H bond oxidation products of toluene was increased from 50.1 to 100%. Meanwhile, the abundant active Ti3+ sites were stabilized in reduced TiO2 by Pt atoms, leading to a rising yield of the primary C-H oxidation products of 249.8 mmol gcat-1. The reported strategy holds great promise for selective oxidation with enhanced selectivity.
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Bacterial infections have become a great threat to public health in recent years. A primary lysozyme is a natural antimicrobial protein; however, its widespread application is limited by its instability. Here, we present a poly (N-isopropylacrylamide) hydrogel inverse opal particle (PHIOP) as a microcarrier of lysozyme to prolong and enhance the efficiency against bacteria. This PHIOP-based lysozyme (PHIOP-Lys) formulation is temperature-responsive and exhibits long-term sustained release of lysozyme for up to 16 days. It shows a potent antibacterial effect toward both Escherichia coli and Staphylococcus aureus, which is even higher than that of free lysozyme in solution at the same concentration. PHIOPs-Lys were demonstrated to effectively inhibit bacterial infections and enhance wound healing in a full-thickness skin wound rat model. This study provides a novel pathway for prolonging the enzymatic activity and antibacterial effects of lysozyme.
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Antiinfecciosos , Muramidasa , Ratas , Animales , Muramidasa/farmacología , Preparaciones de Acción Retardada/farmacología , Antibacterianos/farmacología , Escherichia coliRESUMEN
Metal sulfides are regarded as efficient scavengers for heavy metals. However, the heavy metal adsorption capacity of metal sulfides is far from its theoretical values due to the insufficient exposure of adsorption sites. Surface modification of metal sulfides is considered one of the most effective strategies for improving heavy metal removal performance. Here, microalgae-derived carbon quantum dots (CQDs) were used as a green modifier for mediating nano-MnS/FeS formation to enhance Cd2+ removal. With the addition of 1 wt% CQDs, the Cd2+ adsorption capacity of 1 %CQDs-MnS reached 481 mg/g at 25 °C and 648.6 mg/g at 45 °C, which surpassed most of the previously reported metal sulfides. Furthermore, the CQDs-modified MnS displayed a better Cd2+ removal capacity than the commercial modifier sodium alginate. The mechanism analysis suggested that decreasing the particle size to expose more adsorption sites and providing additional chelating sites derived from the CQDs are two main reasons why CQDs enhance the Cd2+ adsorption capacity of metal sulfides. This study presents an exceptional cadmium nano-adsorbent of 1 %CQDs-MnS and provides a new perspective on the enhancement of heavy metal removal by using CQDs as a promising and universal green modifier that mediates the formation of metal sulfides.
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Metales Pesados , Microalgas , Puntos Cuánticos , Cadmio , Carbono , Adsorción , Alginatos , SulfurosRESUMEN
Bisphenols, parabens, and their metabolites are a group of chemical compounds with a wide range of polarities but similar chemical structures, which presents a challenge for the simultaneous determination of these compounds in complex biological samples. In this study, a rapid and sensitive method for simultaneous quantification of free bisphenol A (BPA), conjugated BPA, bisphenols, and parabens analogs was developed using solid-phase extraction (SPE) tandem liquid-liquid extraction (LLE). We compared the effects of different types of SPE cartridges, diluents, and LLE solvents on the analyte recovery. Utilizing the direct and indirect determination methods (enzyme hydrolysis), we confirmed the accuracy of the direct method for measuring BPA glucuronide and BPA disulfate. The method enabled the analysis of 24 endocrine-disrupting chemicals (EDCs) in one injection through UHPLC-MSMS measurements, with satisfactory recovery (mean: 91.8-98.6% for urine, 80.2%-96.8% for serum) and precision (RSD <15%). The LOD and LOQ values were 0.003 and 0.01 ng/mL for serum, and 0.002 and 0.006 ng/mL for urine samples, respectively. For real sample analysis, the median concentration of analytes in serum and urine samples ranged from 0.04 ng/mL (BPS) to 56.4 ng/mL (4-HB) and 0.11 ng/mL (BPA) to 136 ng/mL (4-HB), respectively. This method provides a new strategy to simultaneously identify compounds with a wide range of polarities from complicated biological matrices.
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Disruptores Endocrinos , Compuestos de Bencidrilo/análisis , Disruptores Endocrinos/análisis , Humanos , Parabenos/análisis , Extracción en Fase Sólida/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
Silver nanoparticles (AgNPs) have been widely used in biomedical and consumer products. It remains challenging to distinguish the toxicity of AgNPs derived from the particle form or the released silver ions (Ag+). In this study, the toxic effects of two citrate-coated AgNPs (20 and 100 nm) and Ag+ were investigated in hepatoblastoma cells (HepG2 cells). The suppression tests showed that AgNPs and Ag+ induced cell apoptosis via different pathways, which led us to speculate on the AgNP-induced mitochondrial damage. Then, the mitochondrial damages induced by AgNPs and Ag+ were compared under the same intracellular Ag+ concentration, showing that the mitochondrial damage might be mainly attributed to Ag nanoparticles but not to Ag+. The interaction between AgNPs and mitochondria was analyzed using a scattered light imaging method combined with light intensity profiles and transmission electron microscopy. The colocalization of AgNPs and mitochondria was observed in both NP20- and NP100-treated HepG2 cells, indicating a potential direct interaction between AgNPs and mitochondria. These results together showed that AgNPs induced apoptosis in HepG2 cells through the particle-specific effects on mitochondria.
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Nanopartículas del Metal , Plata , Apoptosis , Células Hep G2 , Humanos , Nanopartículas del Metal/toxicidad , Mitocondrias , Plata/toxicidadRESUMEN
Accurate quantification of number concentration of nanoparticles (NPs) is critical for their biomedical and catalytic applications. We developed a novel NP analysis platform based on coupled gel immobilization and a three-dimensional (3D) scattered light imaging (SLI) platform. This imaging-based technique enables high-throughput analysis of silver nanoparticles (AgNPs) at single-particle level without the need for particle labeling or modification. This is a well-established quantitative characterization technique that can simultaneously measure the number concentration and size distribution of AgNPs. It also demonstrates the visualization and quantification of the size and 3D morphology of AgNP agglomerates in solution.
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Imagenología Tridimensional , Nanopartículas del Metal/química , Imagen Óptica , Plata/química , Geles/química , Tamaño de la PartículaRESUMEN
Nanomaterials are widely used in a variety of industrial, biological, and medical applications. Therefore, high concerns about their possible impact on human and environmental health have been raised. Here, we describe a high-throughput single-cell imaging method to reveal the crosstalk among quantum dot (QDot)-induced ROS generation, apoptosis, and changes in nucleus size in macrophages. In triple marker combinations, we assessed the correlations of three QDot-induced cellular responses via divided subsets based on single-cell analysis. In contrast to the results obtained from the cell population, we demonstrated that the change in nucleus size was positively correlated with ROS generation. We found that QDot exposure induced ROS generation, which led to cell apoptosis, followed by a change in nucleus size. In general, these observations on crosstalk of cellular responses provide detailed insights into the heterogeneity of nanoparticle exposure.
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Nanopartículas , Puntos Cuánticos , Apoptosis , Humanos , Nanopartículas/toxicidad , Puntos Cuánticos/toxicidad , Análisis de la Célula IndividualRESUMEN
Tetrabromobisphenol A (TBBPA) is a widely used flame retardant, but the adverse outcomes induced by TBBPA has not been fully elucidated. In this study, TBBPA was detected in 54.9% of 102 female Chinese volunteers with an average serum concentration of 0.34 ng/mL. To investigate whether TBBPA induces adverse outcomes at environmentally relevant exposure doses, the mice were exposed to TBBPA for 14 and 28 days. The internal doses of TBBPA in mice serum were nearly the internal doses in volunteers. TBBPA significantly increased the secretion of some pro-inflammatory cytokines and suppressed immune responses in mice under such serum concentrations after 14- and 28-days exposure. Interestingly, uterine edema was observed in TBBPA-treated mice. In primary uterine cells model, the results showed TBBPA exposure suppressed THRß expression, leading to the activation of the inflammatory PI3K/NF-κB signaling pathway. Our findings indicated that the uterus is the susceptible target organ of TBBPA and TBBPA exposure might increase risk of uterine cancer through deregulating inflammation pathways.
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Retardadores de Llama , Bifenilos Polibrominados , Animales , Femenino , Retardadores de Llama/toxicidad , Inflamación/inducido químicamente , Ratones , Bifenilos Polibrominados/toxicidad , ÚteroRESUMEN
Tetrachlorobisphenol A (TCBPA) can promote intracellular reactive oxygen species (ROS) accumulation. However, limited attention has been given to mechanisms underlying TCBPA exposure-associated ROS accumulation. Here, such mechanisms were explored in the simple eukaryotic model organism Saccharomyces cerevisiae exposed to multiple concentrations of TCBPA. Addition of diphenyleneiodonium, a specific inhibitor of NADPH oxidase, blocked TCBPA treatment-associated intracellular ROS accumulation. NADPH oxidase can be activated by calcineurin, mitogen-activated protein kinase (MAPK), and tyrosine kinase. Therefore, corresponding specific inhibition respectively on these three kinases was performed and results suggested that the Ca2+ signaling pathway, MAPK pathway, and tyrosine kinase pathway all contributed to the TCBPA exposure-associated intracellular ROS accumulation. In addition, TCBPA exposure-associated up-regulation of genes involved in ROS production and down-regulation of catalase promoted ROS accumulation in S. cerevisiae. To sum up, our current results provide insights into the understanding of TCBPA exposure-associated ROS accumulation.
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Clorofenoles/toxicidad , Retardadores de Llama/toxicidad , Saccharomyces cerevisiae/efectos de los fármacos , Calcio/metabolismo , Catalasa/genética , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , NADPH Oxidasas/antagonistas & inhibidores , Compuestos Onio/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa-1/genéticaRESUMEN
Dressings coated with silver nanoparticle (AgNP) are widely used in the management of acute and chronic wounds. However, whether AgNP exerts toxicity on wound healing remains ambiguous. To demonstrate the effects of AgNP on wound healing, we precisely quantified the recovery speed of wound by taking advantage of the fin regeneration of zebrafish. This method also enabled assessment of the adverse effect of AgNP on various steps of wound healing in vivo. We revealed that AgNP treatment at the concentration of 2 µg/ml impaired fin regeneration when exposure was performed at the phases of epithelialization and the beginning of blastema formation. Cell proliferation of regenerative blastema was significantly decreased after AgNP exposure. But the canonical signals including Wingless/Integrated (Wnt), Notch and Fibroblast growth factor (Fgf) which play important roles in cell proliferation during fin regeneration were not modulated at 36 hours post amputation (hpa). Further study showed that AgNP impaired fin regeneration through declining amputation-induced ROS as early as epithelialized phase at 18 hpa, rather than inducing ROS generation. AgNP exposure also promoted recruitment of neutrophils in the early phase of wound healing, which suggests that this event dampened amputation-induced ROS. Overall, this study suggested that application of AgNP-coated dressings should be carefully considered at the beginning stage of wound healing.
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Nanopartículas del Metal , Pez Cebra , Aletas de Animales , Animales , Proliferación Celular , Regeneración , Plata , Cicatrización de HeridasRESUMEN
Safety concerns have been raised with regard to silver nanowires (AgNWs) because of their extensive applications. Recently, ultralong AgNWs have shown physical properties superior to those of short AgNWs. However, little is known about their toxicity and potential risks. In this study, we demonstrated a series of ultralong AgNWs-induced biological effects in human lung cancer epithelial cells (A549). Ultralong AgNWs treatments induced ROS generation, mitochondria-mediated apoptosis, and self-protective autophagy at nonlethal concentrations. In contrast to some previous reports, apoptosis was found not to correlate with the reduction of intracellular ROS. Measuring the processing of ROS generation, apoptosis and autophagy, we demonstrated that ROS not only enhance mitochondrial damage, but also raise protective autophagic flux in ultralong AgNW-treated cells. Moreover, ultralong AgNWs were found to be internalized into the cytoplasm of the epithelial cells. This study not only investigates ultralong AgNWs-induced cytotoxicity but also pinpoints ROS as a key signal in mechanisms of their toxicity.