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1.
Food Chem Toxicol ; 164: 113018, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35430334

RESUMO

Activated microglia play an active role in the pathogenesis of PD and paraquat (PQ) induces PD. The study was to understand the time relationship between microglial activation and dopaminergic neuron loss in the substantia nigra (SN) of PQ-induced PD mice. Male C57BL/6 mice were injected intraperitoneally with PQ, twice a week for six weeks. Some mice underwent behavioral assessments each week and were sacrificed for SN tissues, in which histopathological analysis, dopaminergic neuron loss, microglial activation and phenotypic characteristics were evaluated. The results showed that motor retardation, coordination disorders and limb stiffness occurred four weeks after PQ exposure, as well as the degeneration and loss of dopaminergic neurons in the SN. Activated microglia and increased CD68 expression appeared two weeks after PQ exposure in time-dependent manners. Increased CD86 and decreased CD206 expression were observed four weeks after PQ exposure, accompanied by increased TNF-α and IL-6 levels and decreased IL-10 and TGF-ß levels. These results indicate that PQ can activate microglia in vivo, and microglial activation precedes neuronal loss in the SN. Activated microglia are characterized by mixed M1/M2 polarization in the early stage and M1 polarization in the late stage of PQ-induced PD development.

2.
Ecotoxicol Environ Saf ; 230: 113105, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34954678

RESUMO

Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.

3.
Comput Biol Chem ; 89: 107397, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33035753

RESUMO

Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Osteoartrite/tratamento farmacológico , Artrite Reumatoide/genética , Diferenciação Celular/efeitos dos fármacos , Bases de Dados de Produtos Farmacêuticos/estatística & dados numéricos , Medicamentos de Ervas Chinesas/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Osteoartrite/genética , Osteoclastos/citologia , Farmacologia/métodos , Mapas de Interação de Proteínas
5.
Environ Int ; 135: 105369, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31841803

RESUMO

Effluents from wastewater treatment plants (WWTPs) may contain various pollutants with potential toxic effects. Ozonation is widely applied to purify wastewater, which may influence the toxicity and water quality indices simultaneously. The main goal of this study was to reveal influence of ozonation on toxicity of WWTP effluents and to find the surrogates for toxicity changes. Cytotoxicity and DNA double-strand break (DSB) effect of WWTP effluents were measured based on Chinese hamster ovary (CHO) cells. Changes of water quality parameters and molecular weight distribution of WWTP effluents were also measured. The organic extracts in WWTP effluents were shown to decrease the cell viability. Besides, an increased level of DNA DSBs was found in cells when exposed to the organic extracts. Ozonation significantly eliminated cytotoxicity and DNA DSB-based genotoxicity of WWTP effluents, with removal rates of 53-66% and 51-76% for cytotoxicity and genotoxicity, respectively, with 10 mg/L ozone dose. Although the DOC contents in WWTP effluents were hardly removed by ozonation, the chromophores and fluorophores were significantly eliminated. Organic matter in WWTP effluents mainly consists of fractions with molecular weight (MW) < 500 Da. Ozonation generally decreased the fluorescence intensity and UV254 values of all the MW fractions, but increased the DOC contents of the 100-500 Da fraction. During ozonation, the removal rates of UV254 and SUVA254 were significantly correlated to the removal rates of both cytotoxicity and genotoxicity. UV254 might be an ideal surrogate for cytotoxicity and genotoxicity reduction during wastewater ozonation.


Assuntos
Quebras de DNA de Cadeia Dupla , Animais , Células CHO , Cricetinae , Cricetulus , Ozônio , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Purificação da Água
6.
Front Oncol ; 9: 710, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417875

RESUMO

Purpose: The expression and role of sperm protein antigen 17 (SPA17), which has been confirmed to be immunogenic, in breast cancer remain unclear. We examined the expression of SPA17 in breast cancer and assessed its effect on patient prognosis and its function in breast cancer development. Methods: SPA17 expression was evaluated by immunohistochemistry and Q-RT-PCR in 120 breast tissue samples. Correlation of SPA17 expression with the patients' clinicopathological parameters and overall survival was assessed. The function of SPA17 was also explored. Results: By reviewing Gene Expression Omnibus datasets, we found that SPA17 expression in ductal breast carcinoma in situ (log2[fold change] = 1.14, p-value = 0.004) and invasive ductal breast cancer (log2[fold change] = 1.03, p-value = 0.016) tissues was 2.20 and 2.05 times higher, respectively, than that in normal breast tissues. Our result also showed that 27% (27/100) of breast cancer samples expressed SPA17 but none of the normal breast (0/20) samples did. Lymph node metastasis (p < 0.001) and molecular subtyping (p = 0.002) were independent factors associated with SPA17 expression. Most importantly, SPA17 expression resulted in poor prognosis. In addition, cell function assay validated that SPA17 increased the migration (p < 0.001) and invasion (p = 0.007) of breast cancer cells, but not affected the proliferation of breast cancer cells. Conclusion: Our results demonstrated the vital role of SPA17 in the development and metastasis of breast cancer and that SPA17 may be a new therapeutic target in improving breast cancer prognosis.

7.
Water Res ; 162: 43-52, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254885

RESUMO

Ozonation is widely used in wastewater treatment but the associated byproduct formation is a concern. When ozonation is used in the presence of bromide, bromate is generally considered as a major byproduct, and few studies have examined the toxicity of organic byproducts. This study was designed to investigate the cytotoxicity, genotoxicity and DNA/RNA oxidative damage to Chinese hamster ovary (CHO) cells of organic extracts from ozonated wastewater in the absence or presence of bromide. Ozonation effectively detoxified secondary effluents containing no bromide. However, ozonation significantly increased the cytotoxicity and genotoxicity of the effluents spiked with a bromide concentration as low as 100 µg/L, compared with the bromide-free effluent. When the bromide concentration in the effluent was increased to 2000 µg/L, ozonation resulted in 1.4-1.5 times the cytotoxicity and 1.5-5.0 times the genotoxicity of the non-ozonated secondary effluent. Besides, the oxidative stress (including reactive oxygen species and reactive nitrogen species) and DNA/RNA oxidative damage also became more severe and a high level of 8-hydroxy-(deoxy)guanosine was detected in the CHO cell nucleus in the presence of bromide. Cytotoxicity and genotoxicity were found to increase with the formation of total organic bromine (TOBr). When the CHO cells were exposed to both the organic byproducts and bromate formed from wastewater containing 500 and 2000 µg/L bromide, bromate significantly increased oxidative stress and DNA/RNA oxidative damage at relatively high concentration factors, suggesting both organic byproduct and bromate can contribute to toxicity increase. During ozonation of the effluent containing bromide, particular attention should be paid to the organic byproducts such as TOBr.


Assuntos
Ozônio , Poluentes Químicos da Água , Purificação da Água , Animais , Bromatos , Brometos , Células CHO , Cricetinae , Cricetulus , Águas Residuárias
8.
Artigo em Inglês | MEDLINE | ID: mdl-29636786

RESUMO

Objective: To compare the expressions of miRNAs (microRNAs) in serum exosomes and in hippocampus and to provide insights into the miRNA-mediated relationship between peripheral and central nervous systems in the presence of methamphetamine. Methods: Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine were replicated. The expressions of miRNAs in serum exosomes and hippocampus were determined by gene-chip sequencing. We then predicted the potential target genes of selected, differentially expressed (DE) miRNAs and then carried out functional analysis of these target genes. We also verified our results by RT-qPCR. Results: Methamphetamine reward could greatly increase the activity time and distance in the intrinsically nonpreferred side of the behavioral apparatus compared with control rats (P < 0.01). Rhynchophylline treatment significantly counteracted these changes (P < 0.01). Methamphetamine-induced CPP upregulated 23 miRNAs (log2 fold change [FC] > 1, P < 0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate these miRNAs (log2 FC < -1, P < 0.01). Analysis of hippocampal miRNAs profiles found 22 DE miRNAs (log2 FC > 1 or <-1, P < 0.01). When methamphetamine induced CPP, 11 of those miRNAs were upregulated, whereas rhynchophylline treatment could downregulate these miRNAs. The other 11 miRNAs behaved in the opposite way. We selected six DE miRNAs from each of serum exosomes and hippocampus for target gene prediction and functional analysis. We found that, in both, the DE miRNAs and their target genes may be related to neuronal information transmission and synaptic transmission. Conclusions: Rhynchophylline blocked the alteration of behavior and the expression of some DE miRNAs induced by methamphetamine. The biological functions of these DE miRNAs target genes are correlated between serum exosomes and hippocampus. As to these biological processes and pathways which are involved in the development of addiction at multiple stages, we speculate that these DE miRNAs in serum exosomes and hippocampus are closely related to methamphetamine addiction.

9.
ARS med. (Santiago, En línea) ; 43(2): 17-24, 2018. Tab
Artigo em Espanhol | LILACS | ID: biblio-1022835

RESUMO

Establecer un score genético utilizando los polimorfismos de nucleótido único (SNPs) del gen que codifica para Ribonucleasa L (RNASEL)y regiones cromosómicas 8q24 y 17q12-24 en combinación con el antígeno específico de la próstata (PSA) para predecir la agresividad del cáncer de próstata (CaP). Pacientes y métodos: hombres con CaP tratados con prostatectomía radical. Se analizaron variables clínicas y patológicas: edad al diagnóstico, PSA al diagnóstico, el volumen tumoral (TV) y extensión extracapsular (ECE) según el TNM (tumour, node and metastasis) (ECE ≥T3) y score de Gleason. Desarrollamos un modelo de puntaje genético usando regresión logística multivariable. Resultados: se incluyeron 86 pacientes sometidos a prostatectomía radical. Edad promedio fue de 62 ± 7,5 años. El promedio de PSA fue de 11,3 ± 10,6 ng/mL. Treinta y un pacientes (36 por ciento) tuvieron ECE. La mediana del TV fue de 3,8 cc. Un PSA ≥ 10 ng/mL se asoció con una mayor tasa de ECE (p <0,05) y TV más alto (p = 0,032). En el análisis univariable, los pacientes con > 1 SNP tienen mayor riesgo de ECE que los pacientes con ≤ 1 SNP (42 por ciento vs. 10,5 por ciento, p = 0,01), y los pacientes con ≥ 3 SNP tienen más TV que los pacientes con <3 SNP (60 por ciento vs. 32 por ciento, p = 0,015). Se crearon dos modelos de riesgo usando el número de SNP y PSA ≥ o <10 ng/mL para predecir ECE (sensibilidad 67 por ciento y especificidad 84 por ciento) y TV (sensibilidad 59 por ciento y especificidad 70 por ciento). Conclusiones: El score genético presentado en este estudio es una herramienta novedosa para predecir indicadores de agresividad del CaP, como ECE y TV.(AU)


To establish a genetic score using SNPs (from RNAsel and chromosomal regions 8q24 and 17q12-24) in combination with Prostate Specific Antigen (PSA) at diagnosis to predict aggressiveness of PCa (tumor volume (TV) and extracapsular extension (ECE)). Patients and methods: Men with PCa diagnosed by needle biopsy and treated with radical prostatectomy (RP). Clinical and pathological variables such as age at diagnosis, PSA at diagnosis, TV, extension of tumor according TNM (ECE ≥T3) and Gleason score where analyzed. We developed a genetic score model using Multivariate Logistic Regression. Results: We included 86 patients who underwent RP. Mean age 62 ± 7.5 years. Mean PSA was 11.3 ± 10.6 ng/mL. Thirty-one patients (36 percent) had ECE. Median TV was 3.8 cc. PSA ≥ 10 ng/mL was associated with increased rate of ECE (p <0.05) and higher TV (p = 0.032). In univariate analysis, patients with more than 1 SNP had a greater risk of ECE than patients with ≤ 1 SNP (42 percent vs. 10.5 percent, p = 0.01), and patients with ≥ 3 risk SNPs had more TV than patients with <3 SNPs risk (60 percent vs. 32 percent, p = 0.015). Two models of risk using the number of SNPs and PSA ≥ or <10 ng/mL to predict ECE (sensitivity 67 percent and specificity 84 percent) and TV (sensitivity 59 percent and specificity 70 percent) were created. Conclusions: Genetic score usingdescribed SNPs and preoperative PSA can predict aggressiveness of PCa, which would be useful to define a management with more information at diagnosis especially in localized cancers.(AU)


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Neoplasias da Próstata , Gradação de Tumores , Antígeno Prostático Específico , Polimorfismo de Nucleotídeo Único
10.
Medicine (Baltimore) ; 96(34): e7787, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28834882

RESUMO

Reducing the false negative rate of sentinel lymph node biopsy (SLNB) for breast cancer patients has always been a focus of clinical research. We aimed to map the sentinel lymph nodes (SLNs) in detail, and analyze the factors related to SLNs located at locations that are often ignored by surgeons, to reduce the rate of false negatives from SLNB. A retrospective analysis involving 545 breast cancer patients who underwent SLNB in west China hospital between August 2010 and February 2016 was performed. Blue dye, radioisotope, or combined methods were used for tracing SLNs. Using blue dye, radioisotope, and a combination of blue dye and radioisotope successfully traced SLNs in 479, 507, and 525 patients, the detection rate was 88.2%, 93.9%, and 97.4%, respectively. Among the 1559 detected SLNs, 139 (9.6%) were located at the latissimus dorsi lateral margin, and 108 (6.9%) were located at level 2. Subcutaneous injection of radioisotope (P = .004) and intradermal injection of blue dye (P = .002) were independent factors associated with SLNs distributed at level 2 and the latissimus dorsi lateral margin, respectively. It was noteworthy that 2 of 7 patients had skipping metastasis in level 2, so subcutaneous injection of the isotope is strongly recommended for tracing SLNs distributed in level 2 because of the possibility of skipping metastasis. Though intradermal injection of blue dye was superior methods for tracing SLNs located at the latissimus dorsi lateral margin, we surprisingly found those patients with metastasis to the latissimus dorsi lateral margin nodes also could have metastasis to level 1 (expect for the latissimus dorsi lateral margin) nodes, it seemed that maybe there is no need to excise SLNs at the latissimus dorsi lateral margin in SLNB, whether such nodes should be regarded as useful for SLNB still needs to be determined by further large, multicenter clinical studies.


Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/normas , Linfonodo Sentinela/patologia , Reações Falso-Negativas , Feminino , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Estudos Retrospectivos
11.
J Environ Sci (China) ; 58: 51-63, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28774626

RESUMO

Chlorination is essential to the safety of reclaimed water; however, this process leads to concern regarding the formation of disinfection byproducts (DBPs) and toxicity. This study reviewed the formation and control strategies for DBPs and toxicity in reclaimed water during chlorination. Both regulated and emerging DBPs have been frequently detected in reclaimed water during chlorination at a higher level than those in drinking water, indicating they pose a greater risk to humans. Luminescent bacteria and Daphnia magna acute toxicity, anti-estrogenic activity and cytotoxicity generally increased after chlorination because of the formation of DBPs. Genotoxicity by umu-test and estrogenic activity were decreased after chlorination because of destruction of toxic chemicals. During chlorination, water quality significantly impacted changes in toxicity. Ammonium tended to attenuate toxicity changes by reacting with chlorine to form chloramine, while bromide tended to aggravate toxicity changes by forming hypobromous acid. During pretreatment by ozonation and coagulation, disinfection byproduct formation potential (DBPFP) and toxicity formation potential (TFP) occasionally increase, which is accompanied by DOC removal; thus, the decrease of DOC was limited to indicate the decrease of DBPFP and TFP. It is more important to eliminate the key fraction of precursors such as hydrophobic acid and hydrophilic neutrals. During chlorination, toxicities can increase with the increasing chlorine dose and contact time. To control the excessive toxicity formation, a relatively low chlorine dose and short contact time were required. Quenching chlorine residual with reductive reagents also effectively abated the formation of toxic compounds.


Assuntos
Desinfetantes/análise , Purificação da Água/métodos , Animais , Desinfetantes/toxicidade , Desinfecção/métodos , Halogenação , Humanos , Poluentes Químicos da Água
12.
Oncotarget ; 8(26): 42455-42465, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28418916

RESUMO

Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast carcinoma. It is presumed to be more aggressive than invasive ductal carcinoma (IDC), though it is uncertain whether the prognoses of IMPC and IDC differ. In this retrospective study, we compared the clinicopathologic characteristics and survival between 170 female patients with IMPC (pure or mixed with IDC) and 728 with pure IDC. The IMPC patients had higher clinical stages and histologic grades, higher incidences of lymphovascular invasion and axillary lymph node extracapsular extension, and a higher degree of lymph node involvement than IDC patients. Moreover, IMPC was associated with increases in estrogen receptor (ER) and progesterone receptor (PR) positivity and HER-2 overexpression. Although locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) were poorer in IMPC patients than IDC patients, overall survival and distant metastasis survival did not differ between the two groups. Multivariate analysis revealed that IMPC was an independent prognostic factor for LRRFS in breast cancer, and IMPC patients had poorer clinicopathologic characteristics and poorer RFS and LRRFS than IDC patients. We therefore suggest that to improve treatment decisions, patients with breast carcinoma be tested for the presence of this specific subtype.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Papilar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Papilar/mortalidade , Carcinoma Papilar/terapia , Terapia Combinada , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(4): 889-93, 2015 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-26197569

RESUMO

Abstract In the present paper, we reported the luminescence properties of BiOCl:Dy(3+) and BiOCl:Dy(3+), Li+ phosphor synthesized by conventional solid state method. X-ray diffraction (XRD) and excitation and emission spectroscopy were used to characterize the samples. Results show that pure tetragonal BiOCl:Dy(3+) crystals can be synthesized successfully at 500 °C, and Li+ ion dopant improves the crystallinity of samples furtherly. Under near UV light excitation, the samples,give the characteristic luminescence of Dy(3+) ions located at 478 (blue) and 574 nm (yellow), which show a low yellow-to-blue intensity ratio (Y/B) of Dy(3+) emission and white light emission. Moreover, codoping of Li+ ion can realize the enhancement of emission intensity and the adjustment of emission color. The characteristics of BiOCl:Dy(3+) phosphor, low temperature preparation, good near ultraviolet excitation and white light emission make it to a promising near-ultraviolet WLED phosphor.

14.
J Pharm Anal ; 4(5): 345-350, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29403899

RESUMO

A gas chromatography mass spectrometry (GC-MS) method has been developed and fully validated for the simultaneous determination of natural borneol (NB) and its metabolite, camphor, in rat plasma. Following a single liquid-liquid extraction, the analytes were separated using an HP-5MS capillary column (0.25 mm×30 m×0.25 µm) and analyzed by MS in the selected ion monitoring mode. Selected ion monitor (m/z) of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats.

15.
Asian Pac J Cancer Prev ; 14(8): 4635-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24083716

RESUMO

Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase Π (GST-Π) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-κB and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Western Blotting , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Glutationa/metabolismo , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Vimblastina/farmacologia , Vinorelbina
16.
J Agric Food Chem ; 61(32): 7855-62, 2013 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-23889173

RESUMO

The use of nanomaterials in consumer products is rapidly expanding. In most studies, nanomaterials are examined as isolated ingredients. However, consumer products such as foods, cosmetics, and dietary supplements are complex chemical matrixes. Therefore, interactions between nanomaterials and other components of the product must be investigated to ensure the product's performance and safety. Silver nanomaterials are increasingly being used in food packaging as antimicrobial agents. Thiol-containing compounds, such as reduced glutathione (GSH), cysteine, and dihydrolipoic acid, are used as antioxidants in many consumer products. In the current study, we have investigated the interaction between silver nanomaterials and thiol-containing antioxidants. The selected Ag nanomaterials were Ag coated with citrate, Ag coated with poly(vinylpyrrolidone), and Au nanorods coated with Ag in a core/shell structure. We observed direct quenching of the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) by all three Ag nanomaterials to varying degrees. The Ag nanomaterials also reduced the quenching of DPPH by GSH to varying degrees. In addition, we determined that the mixture of GSH and Au@Ag nanorods held at 37 °C was less effective at quenching azo radical than at ambient temperature. Furthermore, we determined that Au@Ag nanorods significantly reduced the ability of GSH and cysteine to quench hydroxyl and superoxide radicals. The work presented here demonstrates the importance of examining the chemical interactions between nanomaterials used in products and physiologically important antioxidants.


Assuntos
Antioxidantes/química , Nanoestruturas/química , Prata/química , Compostos de Sulfidrila/química
17.
Nanoscale ; 5(4): 1583-91, 2013 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-23329011

RESUMO

Au@Pt nanorods were prepared by growing platinum nanodots on gold nanorods. Using electron spin resonance (ESR), we determined that the mechanisms for oxidation of ascorbic acid (AA) by Au@Pt nanorods and ascorbic acid oxidase (AAO) were kinetically similar and yielded similar products. In addition we observed that Au@Pt nanorods were stable with respect to temperature and pH. Using UV-VIS spectroscopy, the apparent kinetics of enzyme-mimetic activity of Au@Pt nanorods were studied and compared with the activity of AAO. With the help of ESR, we found that Au@Pt nanorods did not scavenge hydroxyl radicals but inhibited the antioxidant ability of AA for scavenging hydroxyl radicals produced by photoirradiating solutions containing titanium dioxide and zinc oxide. Moreover, the Au@Pt nanorods reduced the ability of AA to scavenge DPPH radicals and superoxide radicals. These results demonstrate that Au@Pt nanorods can reduce the antioxidant activity of AA. Therefore, it is necessary to consider the effects of using Pt nanoparticles together with other reducing agents or antioxidants such as AA due to the oxidase-like property of Au@Pt nanorods.


Assuntos
Antioxidantes/química , Ácido Ascórbico/química , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Platina/química , Ativação Enzimática , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Oxirredutases/química , Tamanho da Partícula , Propriedades de Superfície
18.
Biomaterials ; 34(3): 765-73, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23103160

RESUMO

Gold nanoparticles have received a great deal of interest due to their unique optical and catalytic properties and biomedical applications. Developing applications as well as assessing associated risks requires an understanding of the interactions between Au nanoparticles (NPs) and biologically active substances. In this paper, electron spin resonance spectroscopy (ESR) was used to investigate the catalytic activity of Au NPs in biologically relevant reactions. We report here that Au NPs can catalyze the rapid decomposition of hydrogen peroxide. Decomposition of hydrogen peroxide is accompanied by the formation of hydroxyl radicals at lower pH and oxygen at higher pH. In addition, we found that, mimicking SOD, Au NPs efficiently catalyze the decomposition of superoxide. These results demonstrate that Au NPs can act as SOD and catalase mimetics. Since reactive oxygen species are biologically relevant products being continuously generated in cells, these results obtained under conditions resembling different biological microenvironments may provide insights for evaluating risks associated with Au NPs.


Assuntos
Ouro/metabolismo , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Nanopartículas/química , Superóxidos/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Catalase/metabolismo , Catálise , Ouro/química , Humanos , Nanopartículas/ultraestrutura , Oxirredução , Superóxido Dismutase/metabolismo
19.
Am J Chin Med ; 40(6): 1271-88, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23227797

RESUMO

Kava is one of the most widely sold herbal dietary supplements in the United States. It has been reported that, besides exhibiting hepatotoxicity, kava also possesses photosensitivity and induces dermopathy in humans. In this study, we determined that UVA irradiation of kava in the presence of a lipid, methyl linoleate, generated lipid peroxidation which was mediated by singlet oxygen generated during photoirradiation. The six major kavalactones(yangonin, 7,8-dihydrokawa in, kawain, 7,8-dihydromethysticin, methysticin, and 5,6-dehydrokawain) were also studied in parallel; only 5,6-dehydrokawain and yangonin-induced a low level of lipid peroxidation. UVA irradiation of kava in human HaCaT skin keratinocytes induced cytotoxicity which was mediated by oxidative stress, led to DNA strand cleavage, and produced 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct. Study by the electron spin resonance (ESR) method revealed that UVA irradiation of kava produced singlet oxygen and carbon-centered radicals. The overall results suggest that kava is photocytotoxic and photogenotoxic, both mediated by free radicals generated during photoirradiation.


Assuntos
Dano ao DNA , Kava/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Espectroscopia de Ressonância de Spin Eletrônica , Imunofluorescência , Humanos , Imuno-Histoquímica
20.
Adv Mater ; 24(39): 5391-7, 2012 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-22927326

RESUMO

Graphene oxide shows stress-induced toxicity properties in vivo under different pathophysiological conditions. A dual-path chemical mechanism, involving the overproduction of hydroxyl radicals and the formation of oxidizing cytochrome c intermediates, is responsible for the toxicity properties.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Grafite/química , Grafite/toxicidade , Nanoestruturas/toxicidade , Estresse Oxidativo , Óxidos/química , Animais , Caenorhabditis elegans/metabolismo , Óxidos N-Cíclicos/química , Óxidos/toxicidade , Polietilenoglicóis/química , Polilisina/química
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