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1.
Cancer Cell Int ; 24(1): 59, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321552

RESUMEN

Peroxiredoxin 3 (PRDX3), a mitochondrial hydrogen peroxide scavenger, is known to be upregulated during tumorigenesis and cancer progression. In this study, we provide evidence for the first time that PRDX3 could regulate cellular signaling pathways associated with Matrix Metalloproteinase-1 (MMP-1) expression and activity in breast cancer progression. We show that shRNA-mediated gene silencing of PRDX3 inhibits cell migration and invasion in two triple-negative breast cancer cell lines. Reciprocal experiments show that PRDX3 overexpression promotes invasion and migration of the cancer cells, processes which are important in the metastatic cascade. Notably, this phenomenon may be attributed to the activation of MMP-1, which is observed to be upregulated by PRDX3 in the breast cancer cells. Moreover, immunohistochemical staining of breast cancer tissues revealed a positive correlation between PRDX3 and MMP-1 expression in both epithelial and stromal parts of the tissues. Further pathway reporter array and luciferase assay demonstrated that activation of ERK signaling is responsible for the transcriptional activation of MMP-1 in PRDX3-overexpressed cells. These findings suggest that PRDX3 could mediate cancer spread via ERK-mediated activation of MMP-1. Targeted inhibition of ERK signaling may be able to inhibit tumor metastasis in triple-negative breast cancer.

2.
Breast Cancer Res Treat ; 186(3): 655-665, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33625616

RESUMEN

PURPOSE: Breast cancer is the most common type of cancer affecting women worldwide. Phosphoglycerate dehydrogenase (PHGDH) is an oxidoreductase in the serine biosynthesis pathway. Although it has been reported to affect growth of various tumors, its role in breast cancer is largely unknown. This study aimed to analyze the expression of PHGDH in breast cancer tissue samples and to determine if PHGDH regulates breast cancer cell proliferation. METHODS: Tissue microarrays consisting of 305 cases of breast invasive ductal carcinoma were used for immunohistochemical evaluation of PHGDH expression. The role of PHGDH in breast cancer was investigated in vitro by knocking down its expression and determining the effect on cell proliferation and cell cycling, and in ovo by using a chorioallantoic membrane (CAM) assay. RESULTS: Immunohistochemical examination showed that PHGDH is mainly localized in the cytoplasm of breast cancer cells and significantly associated with higher cancer grade, larger tumor size, increased PCNA expression, and lymph node positivity. Analysis of the GOBO dataset of 737 patients demonstrated that increased PHGDH expression was associated with poorer overall survival. Knockdown of PHGDH expression in breast cancer cells in vitro resulted in a decrease in cell proliferation, reduction in cells entering the S phase of the cell cycle, and downregulation of various cell cycle regulatory genes. The volume of breast tumor in an in ovo CAM assay was found to be smaller when PHGDH was silenced. CONCLUSION: The findings suggest that PHGDH has a regulatory role in breast cancer cell proliferation and may be a potential prognostic marker and therapeutic target in breast cancer.


Asunto(s)
Neoplasias de la Mama , Fosfoglicerato-Deshidrogenasa , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Fosfoglicerato-Deshidrogenasa/genética , Pronóstico , Serina
3.
Ecotoxicol Environ Saf ; 208: 111702, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396033

RESUMEN

Cellular models exhibiting human physiological features of pseudostratified columnar epithelia, provide a more realistic approach for elucidating detailed mechanisms underlying PM2.5-induced pulmonary toxicity. In this study, we characterized the barrier and mucociliary functions of differentiated human small airway epithelial cells (SAECs), cultured at the air-liquid interface (ALI). Due to the presence of mucociliary protection, particle internalization was reduced, with a concomitant decrease in cytotoxicity in differentiated S-ALI cells, as compared to conventional submerged SAEC cultures. After 24-hour exposure to PM2.5 surrogates, 117 up-regulated genes and 156 down-regulated genes were detected in S-ALI cells, through transcriptomic analysis using the Affymetrix Clariom™ S Human Array. Transcription-level changes in >60 signaling pathways, were revealed by functional annotation of the 273 differentially expressed genes, using the PANTHER Gene List Analysis. These pathways are involved in multiple cellular processes, that include inflammation and apoptosis. Exposure to urban PM2.5 led to complex responses in airway epithelia, including a net induction of downstream pro-inflammatory and pro-apoptotic responses. Collectively, this study highlights the importance of using the more advanced ALI model rather than the undifferentiated submerged model, to avoid over-assessment of inhaled particle toxicity in human. The results of our study also suggest that reduction of ambient PM2.5 concentrations would have a protective effect on respiratory health in humans.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Células Epiteliales/efectos de los fármacos , Material Particulado/toxicidad , Transcriptoma/efectos de los fármacos , Contaminantes Atmosféricos/química , Apoptosis/efectos de los fármacos , Células Cultivadas , Células Epiteliales/metabolismo , Células Epiteliales/patología , Perfilación de la Expresión Génica , Humanos , Tamaño de la Partícula , Material Particulado/química , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética
4.
Ecotoxicol Environ Saf ; 202: 110932, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32800216

RESUMEN

Adverse health effects arising from exposure to fine particulates have become a major concern. Angiogenesis is a vital physiological process for the growth and development of cells and structures in the human body, whereby excessive or insufficient vessel growth could contribute to pathogenesis of diseases. We therefore evaluated indirect effects of carbon black (CB) and inhalable airborne particles on the angiogenic ability of unexposed Human Umbilical Vein Endothelial Cells (HUVECs) by co-culturing HUVECs with pre-exposed Small Airway Epithelial Cells (SAECs). As endothelial cells are major components of blood vessels and potential targets of fine particles, we investigated if lung epithelial cells exposed to ambient PM2.5 surrogates could induce bystander effects on neighboring unexposed endothelial cells in an alveolar-capillary co-culture lung model. Epithelial exposure to CB at a non-toxic dose of 25 µg/mL reduced endothelial tube formation and cell adhesion in co-cultured HUVECs, and decreased expression of angiogenic genes in SAECs. Similarly, exposure of differentiated SAECs to PM2.5 surrogates reduced cell reproductive ability, adhesion and tube formation of neighboring HUVECs. This indicates epithelial exposure to CB and urban PM2.5 surrogates both compromised the angiogenic ability of endothelial cells through bystander effects, thereby potentially perturbing the ventilation-perfusion ratio and affecting lung function.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Material Particulado/toxicidad , Pruebas de Toxicidad , Técnicas de Cocultivo , Células Epiteliales , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Pulmón/metabolismo , Neovascularización Patológica , Hollín
5.
Anal Chem ; 90(10): 6193-6198, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29608843

RESUMEN

Cell surface receptors play an important role in mediating cell communication and are used as disease biomarkers and therapeutic targets. We present a one-pot molecular toolbox, which we term the split proximity circuit (SPC), for the autonomous detection and visualization of cell surface receptor clusters. Detection was powered by antibody recognition and a series of autonomous DNA hybridization to achieve localized, enzyme-free signal amplification. The system under study was the human epidermal growth factor receptor (HER) family, that is, HER2:HER2 homodimer and HER2:HER3 heterodimer, both in cell lysate and in situ on fixed whole cells. The detection and imaging of receptors were carried out using standard microplate scans and confocal microscopy, respectively. The circuit operated specifically with minimal leakages and successfully captured the receptor expression profiles on three cell types without any intermediate washing steps.


Asunto(s)
ADN/química , Receptor ErbB-2/análisis , Receptor ErbB-3/análisis , Ensayo de Inmunoadsorción Enzimática , Humanos , Microscopía Confocal , Células Tumorales Cultivadas
6.
Metabolomics ; 14(9): 118, 2018 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-30830374

RESUMEN

INTRODUCTION: Histologically lung cancer is classified into four major types: adenocarcinoma (Ad), squamous cell carcinoma (SqCC), large cell carcinoma (LCC), and small cell lung cancer (SCLC). Presently, our understanding of cellular metabolism among them is still not clear. OBJECTIVES: The goal of this study was to assess the cellular metabolic profiles across these four types of lung cancer using an untargeted metabolomics approach. METHODS: Six lung cancer cell lines, viz., Ad (A549 and HCC827), SqCC (NCl-H226 and NCl-H520), LCC (NCl-H460), and SCLC (NCl-H526), were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry, with normal human small airway epithelial cells (SAEC) as the control group. The principal component analysis (PCA) was performed to identify the metabolic signatures that had characteristic alterations in each histological type. Further, a metabolite set enrichment analysis was performed for pathway analysis. RESULTS: Compared to the SAEC, 31, 27, 34, 34, 32, and 39 differential metabolites mainly in relation to nucleotides, amino acid, and fatty acid metabolism were identified in A549, HCC827, NCl-H226, NCl-H520, NCl-H460, and NCl-H526 cells, respectively. The metabolic signatures allowed the six cancerous cell lines to be clearly separated in a PCA score plot. CONCLUSION: The metabolic signatures are unique to each histological type, and appeared to be related to their cell-of-origin and mutation status. The changes are useful for assessing the metabolic characteristics of lung cancer, and offer potential for the establishment of novel diagnostic tools for different origin and oncogenic mutation of lung cancer.


Asunto(s)
Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Metabolómica , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Cromatografía Liquida , Humanos , Espectrometría de Masas , Carcinoma Pulmonar de Células Pequeñas/patología , Células Tumorales Cultivadas
7.
Sci Total Environ ; 876: 162704, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-36907397

RESUMEN

The widespread COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) necessitated measures aimed at preventing the spread of SARS-CoV-2. To mitigate the risk of fomite-mediated transmission, environmental cleaning and disinfection regimes have been widely implemented. However, conventional cleaning approaches such as surface wipe downs can be laborious and more efficient and effective disinfecting technologies are needed. Gaseous ozone disinfection is one technology which has been shown to be effective in laboratory studies. Here, we evaluated its efficacy and feasibility in a public bus setting, using murine hepatitis virus (a related betacoronavirus surrogate) and the bacteria Staphylococcus aureus as test organisms. An optimal gaseous ozone regime resulted in a 3.65-log reduction of murine hepatitis virus and a 4.73-log reduction of S. aureus, and decontamination efficacy correlated with exposure duration and relative humidity in the application space. These findings demonstrated gaseous ozone disinfection in field settings which can be suitably translated to public and private fleets that share analogous characteristics.


Asunto(s)
Antiinfecciosos , COVID-19 , Ozono , Ratones , Animales , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Descontaminación/métodos , Staphylococcus aureus , Pandemias/prevención & control , Desinfección/métodos
8.
Acta Pharmacol Sin ; 32(8): 983-90, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21743485

RESUMEN

The rapid advancement of nanotechnology in recent years has fuelled a burgeoning interest in the field of nanoparticle research, in particular, its application in the medical arena. A constantly expanding knowledge based on a better understanding of the properties of gold nanoparticles (AuNPs) coupled with relentless experimentation means that the frontiers of nanotechnology are constantly being challenged. At present, there seems to be heightened interest in the application of AuNPs to the management of cancer, encompassing diagnosis, monitoring and treatment of the disease. These efforts are undertaken in the hope of revolutionizing current methods of treatment and treatment strategies for a multifactorial disease such as cancer. This review will focus on the current applications of AuNPs in cancer management.


Asunto(s)
Oro/administración & dosificación , Nanopartículas del Metal/administración & dosificación , Neoplasias/tratamiento farmacológico , Animales , Oro/química , Humanos , Nanotecnología/métodos , Neoplasias/diagnóstico
9.
J Am Chem Soc ; 132(42): 14803-11, 2010 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-20882976

RESUMEN

In the present study, quantum dot (QD) capped magnetite nanorings (NRs) with a high luminescence and magnetic vortex core have been successfully developed as a new class of magnetic-fluorescent nanoprobe. Through electrostatic interaction, cationic polyethylenimine (PEI) capped QD have been firmly graft into negatively charged magnetite NRs modified with citric acid on the surface. The obtained biocompatible multicolor QD capped magnetite NRs exhibit a much stronger magnetic resonance (MR) T2* effect where the r2* relaxivity and r2*/r1 ratio are 4 times and 110 times respectively larger than those of a commercial superparamagnetic iron oxide. The multiphoton fluorescence imaging and cell uptake of QD capped magnetite NRs are also demonstrated using MGH bladder cancer cells. In particular, these QD capped magnetite NRs can escape from endosomes and be released into the cytoplasm. The obtained results from these exploratory experiments suggest that the cell-penetrating QD capped magnetite NRs could be an excellent dual-modality nanoprobe for intracellular imaging and therapeutic applications. This work has shown great potential of the magnetic vortex core based multifunctional nanoparticle as a high performance nanoprobe for biomedical applications.


Asunto(s)
Óxido Ferrosoférrico , Imagen por Resonancia Magnética/métodos , Nanoestructuras , Puntos Cuánticos , Espectrometría de Fluorescencia/métodos , Humanos , Microscopía Electrónica de Transmisión , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/patología
10.
J Vis Exp ; (151)2019 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-31609321

RESUMEN

Zinc oxide nanoparticles (ZnO NPs) have a wide range of applications, but the number of reports on ZnO NP-associated toxicity has grown rapidly in recent years. However, studies that elucidate the underlying mechanisms for ZnO NP-induced toxicity are scanty. We determined the toxicity profiles of ZnO NPs using both in vitro and in vivo experimental models. A significant decrease in cell viability was observed in ZnO NP-exposed MRC5 lung fibroblasts, showing that ZnO NPs exert cytotoxic effects. Similarly, interestingly, gut exposed to ZnO NPs exhibited a dramatic increase in reactive oxygen species levels (ROS) in the fruit fly Drosophila. More in-depth studies are required to establish a risk assessment for the increased usage of ZnO NPs by consumers.


Asunto(s)
Pulmón/efectos de los fármacos , Pulmón/metabolismo , Nanopartículas del Metal/toxicidad , Nanopartículas/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Óxido de Zinc/toxicidad , Animales , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Drosophila melanogaster , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Humanos , Pulmón/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología
11.
Nanotoxicology ; 13(4): 429-446, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30451554

RESUMEN

Nanomaterials (NMs) are widely used in consumer and industrial products, as well as in the field of nanomedicine. Despite their wide array of applications, NMs are regarded as foreign entities by the body and thus induce various immune reactions. In mammals, NMs trigger differential recognition by immune cells such as macrophages, causing perturbation of the immune system. Studies on the pattern recognition of NMs have revealed that the Toll-like receptor signaling pathway plays an essential role in NM-induced innate immunity. However, effects caused by physicochemical properties of NMs on immune response and how NMs are recognized by immune cells are not fully understood. Furthermore, the complexity of the mammalian immune system and interspecies variation are still being debated, and the discordant results warrant the need to address these issues. Drosophila melanogaster has gained popularity as a model to study nanotoxicity. Drosophila innate immunity has extensively been studied, providing insights into our understanding of key signaling cascades involved, and importantly it has conserved immune-related genes and mechanogenetic pathways that represents a useful basis for studying its biological response at molecular level to environmental contaminants such as NMs. Moreover, various genetic tools and reagents enable to elucidate the molecular mechanisms underlying the internalization of NMs by immune cells. Furthermore, numerous forward and reverse genetic approaches can be employed to dissect complex biological processes, such as identifying signal transduction pathways and their core components involved in NM-induced immune responses. This review presents an overview of Drosophila innate immunity, as well as summarizes the impact of NM exposure on immune response in Drosophila. We also highlight the recent advancement of suitable methodologies and tools regarding the use of Drosophila as a model for studying the immune-related toxicity of NMs, taking into account the limitations associated with studying NM-induced toxicity in the mammalian system.


Asunto(s)
Drosophila melanogaster/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos , Nanoestructuras/toxicidad , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/inmunología , Inmunidad Innata/genética , Transducción de Señal
12.
Nanotoxicology ; 13(8): 1117-1132, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31272252

RESUMEN

Engineered nanomaterials are of public health concern. Recently, there has been an increasing attention on the toxicity of nanoplastics and nanoZnO because of their increasing utilization and presence in the environment. However, knowledge of their toxicological behavior and metabolic interactions with the cellular machinery that determine their potential health effects are extremely limited. In this study, the cellular uptake, cytotoxic effects, and metabolic responses of bronchus epithelial (BEAS-2B) cells exposed to nanopolystyrene (nanoPS) and a widely used metallic nanoparticle, nanoZnO, were investigated using a tandem mass spectrometry-based metabolomics approach. The results revealed that even with low cytotoxicity, these nanoparticles (NPs) affected cell metabolism. NanoPS exposure showed autophagic- and endoplasmic reticulum (ER) stress-related metabolic changes such as increased in amino acids and tricarboxylic acid cycle (TCA) intermediate metabolites, a process known to play a critical role in regulating cell resistance to cytotoxic effects. Both metabolomics profiling and ER-stress pathway, together with quantitative real-time RT-polymerase chain reaction (qRT-PCR) analyses, demonstrated that autophagy was reciprocally regulated to couple metabolic and transcriptional reprograming. In contrast, nanoZnO-induced ROS-mediated cell death was associated with mitochondrial dysfunction and interference in regulating energy metabolism. Collectively, these two types of NPs were observed to cause perturbations albeit differential in cellular metabolism associated with their cytotoxic effects. Our findings provided an in depth understanding of metabolic changes influenced by two different types of NPs, with contrasting molecular mechanisms for the adverse effects observed.


Asunto(s)
Células Epiteliales/efectos de los fármacos , Pulmón/citología , Metabolómica/métodos , Nanopartículas/toxicidad , Óxido de Zinc/toxicidad , Aminoácidos , Transporte Biológico , Línea Celular , Metabolismo Energético/efectos de los fármacos , Humanos , Metaboloma/efectos de los fármacos , Nanopartículas/química , Óxido de Zinc/química
13.
Curr Med Chem ; 25(12): 1409-1419, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28393698

RESUMEN

BACKGROUND: As nanomaterials possess attractive physicochemical properties, immense research efforts have been channeled towards their development for biological and biomedical applications. In particular, zinc nanomaterials (nZnOs) have shown great potential for use in in the medical and pharmaceutical fields, and as tools for novel antimicrobial treatment, thereby capitalizing on their unique antimicrobial effects. METHODS: We conducted a literature search using databases to retrieve the relevant articles related to the synthesis, properties and current applications of nZnOs in the diagnosis and treatment of diseases. A total of 86 publications were selected for inclusion in this review. RESULTS: Besides studies on the properties and the methodology for the synthesis of nZnOs, many studies have focused on the application of nZnOs as delivery agents, biosensors and antimicrobial agents, as well as in bioimaging. CONCLUSION: This review gives an overview of the current development of nZnOs for their potential use as theranostic agents. However, more comprehensive studies are needed to better assess the valuable contributions and the safety of nZnOs in nanomedicine.


Asunto(s)
Nanomedicina/métodos , Nanoestructuras/uso terapéutico , Óxido de Zinc/uso terapéutico , Animales , Humanos , Nanoestructuras/química , Óxido de Zinc/síntesis química , Óxido de Zinc/química
14.
Chem Biol Interact ; 289: 81-89, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29705079

RESUMEN

Gold nanoparticles (AuNPs) have emerging applications in biomedicine and the industry. Exposure to AuNPs has previously been shown to alter the transcriptional activity of nuclear factor kappa B (NF-kB), which is known to mediate physiological and pathological processes. This study seeks to provide mechanistic insights into AuNP-induced NF-kB activation in Small Airway Epithelial Cells (SAECs) in vitro. Increased NF-kB transcriptional activity (quantified by the luciferase reporter assay) was observed in AuNP-treated SAECs. Transcriptomic analysis revealed differential expression of 42 genes, which regulate functional processes that include cellular response to stimulus, chemicals and stress as well as immune response. Notably, the gene expression of serum amyloid A1 (SAA1), an acute phase protein and Toll-like receptor 2 (TLR2) were found to be up-regulated. As TLR2 is known to be a functional receptor of SAA1, a co-immunoprecipitation assay was performed. SAA1 was observed to be co-immunoprecipitated with the TLR2 protein and this protein-protein interaction was further supported by in silico computer based protein modeling. The present study suggests that AuNPs may potentially induce SAA1-TLR2-mediated NF-kB transcription factor activation in lung epithelial cells, highlighting that nano-bio interactions could result in biological effects that may affect cells.


Asunto(s)
Oro/química , Pulmón/metabolismo , Nanopartículas del Metal/química , FN-kappa B/metabolismo , Proteína Amiloide A Sérica/metabolismo , Transducción de Señal , Receptor Toll-Like 2/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/ultraestructura , Perfilación de la Expresión Génica , Humanos , Nanopartículas del Metal/ultraestructura , Modelos Biológicos , Unión Proteica
15.
Int J Nanomedicine ; 12: 1621-1637, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28280330

RESUMEN

BACKGROUND: Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. METHODS: In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. RESULTS: For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. CONCLUSION: The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would be needed to verify the safety issues related to increased usage of ZnO NPs by consumers.


Asunto(s)
Daño del ADN , Drosophila melanogaster/citología , Drosophila melanogaster/efectos de los fármacos , Fibroblastos/patología , Pulmón/patología , Nanopartículas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Óxido de Zinc/toxicidad , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Humanos , Larva/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Nanopartículas/ultraestructura , Especies Reactivas de Oxígeno/metabolismo
16.
ACS Nano ; 11(4): 3614-3631, 2017 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-28371584

RESUMEN

Large-scale synthesis of monodisperse ultrasmall metal ferrite nanoparticles as well as understanding the correlations between chemical composition and MR signal enhancement is critical for developing next-generation, ultrasensitive T1 magnetic resonance imaging (MRI) nanoprobes. Herein, taking ultrasmall MnFe2O4 nanoparticles (UMFNPs) as a model system, we report a general dynamic simultaneous thermal decomposition (DSTD) strategy for controllable synthesis of monodisperse ultrasmall metal ferrite nanoparticles with sizes smaller than 4 nm. The comparison study revealed that the DSTD using the iron-eruciate paired with a metal-oleate precursor enabled a nucleation-doping process, which is crucial for particle size and distribution control of ultrasmall metal ferrite nanoparticles. The principle of DSTD synthesis has been further confirmed by synthesizing NiFe2O4 and CoFe2O4 nanoparticles with well-controlled sizes of ∼3 nm. More significantly, the success in DSTD synthesis allows us to tune both MR and biochemical properties of magnetic iron oxide nanoprobes by adjusting their chemical composition. Beneficial from the Mn2+ dopant, the synthesized UMFNPs exhibited the highest r1 relaxivity (up to 8.43 mM-1 s-1) among the ferrite nanoparticles with similar sizes reported so far and demonstrated a multifunctional T1 MR nanoprobe for in vivo high-resolution blood pool and liver-specific MRI simultaneously. Our study provides a general strategy to synthesize ultrasmall multicomponent magnetic nanoparticles, which offers possibilities for the chemical design of a highly sensitive ultrasmall magnetic nanoparticle based T1 MRI probe for various clinical diagnosis applications.


Asunto(s)
Medios de Contraste/química , Compuestos Férricos/síntesis química , Imagen por Resonancia Magnética , Compuestos de Manganeso/síntesis química , Simulación de Dinámica Molecular , Nanopartículas/química , Temperatura , Animales , Supervivencia Celular/efectos de los fármacos , Femenino , Compuestos Férricos/química , Compuestos Férricos/farmacología , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie
17.
ACS Biomater Sci Eng ; 2(11): 1959-1967, 2016 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-33440531

RESUMEN

Potential adverse effects of gold nanoparticles (AuNPs) are gaining attention due to their wide industrial, consumer, and biomedical applications. This may give rise to possible health risks from direct exposure to the NPs. Excessive inflammatory response is known to be one of the main effects induced by NPs. In this study, inflammatory and miRNA expression changes in lung tissues were evaluated in rats following intravenous administration of AuNPs. AuNPs (20 nm) at a mass concentration of 256 µg/mL were intravenously injected into 6-8 week old male Wistar rats at single doses of 0.025, 0.05, 0.1, and 0.2 mg/kg and sacrificed at 1 week, 1 month, and 2 months, respectively. The biodistribution of AuNPs in the lungs of the rats was determined by inductively coupled plasma mass spectrometry. There were no apparent changes observed in the body weight of the experimental rats. Histopathological examination revealed the presence of infiltrating lymphocytes in lung interstitial tissues and enhanced IL-1α immunostaining in the lung tissues. Out of 84 rat microRNAs (miRNAs) analyzed, the expression of three miRNAs in rat lungs were dysregulated by more than 2-fold in the 0.1 and 0.2 mg/kg AuNP-treated rats 1 week after exposure. In particular, miR-327 was significantly down-regulated in both groups of treated rats. Taken together, it would seem that miRNAs may regulate inflammatory changes in the lungs after exposure to AuNPs in vivo.

18.
Adv Healthc Mater ; 5(16): 2092-104, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27297640

RESUMEN

Uniform wüstite Fe0.6 Mn0.4 O nanoflowers have been successfully developed as an innovative theranostic agent with T1 -T2 dual-mode magnetic resonance imaging (MRI), for diagnostic applications and therapeutic interventions via magnetic hyperthermia. Unlike their antiferromagnetic bulk counterpart, the obtained Fe0.6 Mn0.4 O nanoflowers show unique room-temperature ferromagnetic behavior, probably due to the presence of an exchange coupling effect. Combined with the flower-like morphology, ferromagnetic Fe0.6 Mn0.4 O nanoflowers are demonstrated to possess dual-modal MRI sensitivity, with longitudinal relaxivity r1 and transverse relaxivity r2 as high as 4.9 and 61.2 mm(-1) s(-1) [Fe]+[Mn], respectively. Further in vivo MRI carried out on the mouse orthotopic glioma model revealed gliomas are clearly delineated in both T1 - and T2 -weighted MR images, after administration of the Fe0.6 Mn0.4 O nanoflowers. In addition, the Fe0.6 Mn0.4 O nanoflowers also exhibit excellent magnetic induction heating effects. Both in vitro and in vivo magnetic hyperthermia experimentation has demonstrated that magnetic hyperthermia by using the innovative Fe0.6 Mn0.4 O nanoflowers can induce MCF-7 breast cancer cell apoptosis and a complete tumor regression without appreciable side effects. The results have demonstrated that the innovative Fe0.6 Mn0.4 O nanoflowers can be a new magnetic theranostic platform for in vivo T1 -T2 dual-mode MRI and magnetic thermotherapy, thereby achieving a one-stop diagnosis cum effective therapeutic modality in cancer management.


Asunto(s)
Neoplasias de la Mama , Medios de Contraste , Compuestos Férricos , Hipertermia Inducida/métodos , Imagen por Resonancia Magnética , Imanes/química , Compuestos de Manganeso , Nanopartículas , Óxidos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Medios de Contraste/síntesis química , Medios de Contraste/química , Medios de Contraste/farmacología , Femenino , Compuestos Férricos/síntesis química , Compuestos Férricos/química , Compuestos Férricos/farmacología , Humanos , Células MCF-7 , Compuestos de Manganeso/síntesis química , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Nanopartículas/química , Nanopartículas/uso terapéutico , Óxidos/síntesis química , Óxidos/química , Óxidos/farmacología , Nanomedicina Teranóstica/métodos
19.
Epigenomics ; 7(3): 395-411, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26077428

RESUMEN

With the growing advent of nanotechnology in medicine (therapeutic, diagnostic and imaging applications), cosmetics, electronics, clothing and food industries, exposure to nanomaterials (NMs) is on the rise and therefore exploring their toxic biological effects have gained great significance. In vitro and in vivo studies over the last decade have revealed that NMs have the potential to cause cytotoxicity and genotoxicity although some contradictory reports exist. However, there are only few studies which have explored the epigenetic mechanisms (changes to DNA methylation, histone modification and miRNA expression) of NM-induced toxicity, and there is a scarcity of information and many questions in this area remain unexplored and unaddressed. This review comprehensively describes the epigenetic mechanisms involved in the induction of toxicity of engineered NMs, and provides comparisons between similar effects observed upon exposure to small or nanometer-sized particles. Lastly, gaps in existing literature and scope for future studies that improve our understanding of NM-induced epigenetic toxicity are discussed.


Asunto(s)
Epigénesis Genética/efectos de los fármacos , Nanopartículas/toxicidad , Metilación de ADN/efectos de los fármacos , Histonas/metabolismo , Nanopartículas del Metal/toxicidad , MicroARNs/metabolismo
20.
Anat Rec (Hoboken) ; 298(2): 418-27, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25243822

RESUMEN

Gold nanoparticles (AuNPs) have potential biomedical and scientific applications. In this study, we evaluated the uptake and internalization of FBS-coated 20 nm AuNPs into lung fibroblasts and liver cells by different microscopy techniques. AuNP aggregates were observed inside MRC5 lung fibroblasts and Chang liver cells under light microscopy, especially after enhancement with automegallography. Clusters of AuNPs were observed to be adsorbed on the cell surface by scanning electron microscopy. Ultrathin sections showed that AuNPs were mainly enclosed within cytoplasmic vesicles when viewed under transmission electron microscopy. We also investigated the mechanism of uptake for AuNPs, using endocytosis inhibitors and quantification of Au with inductively coupled plasma mass spectrometry. Cells treated with concanavalin A and chlorpromazine showed significant decrease of Au uptake in MRC5 lung fibroblasts and Chang liver cells, respectively, implying that the uptake of AuNPs was facilitated by clathrin-mediated endocytosis. It would therefore appear that uptake of 20 nm AuNPs in both cell types with different tissues of origin, was dependent upon clathrin-mediated endocytosis.


Asunto(s)
Clatrina/metabolismo , Endocitosis/fisiología , Fibroblastos/metabolismo , Oro/metabolismo , Nanopartículas del Metal , Línea Celular , Supervivencia Celular , Clatrina/análisis , Fibroblastos/química , Oro/análisis , Humanos , Nanopartículas del Metal/análisis
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