Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
Nat Commun ; 13(1): 136, 2022 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-35013263

RESUMEN

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial ß-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.


Asunto(s)
Proteínas Bacterianas/antagonistas & inhibidores , Carcinógenos/antagonistas & inhibidores , Colitis/prevención & control , Neoplasias Colorrectales/prevención & control , Glucuronidasa/antagonistas & inhibidores , Inhibidores de Glicósido Hidrolasas/farmacología , Triclosán/antagonistas & inhibidores , Animales , Antiinfecciosos Locales/química , Antiinfecciosos Locales/metabolismo , Antiinfecciosos Locales/toxicidad , Anticarcinógenos/química , Anticarcinógenos/farmacología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sitios de Unión , Biotransformación , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Carcinógenos/química , Carcinógenos/metabolismo , Carcinógenos/toxicidad , Colitis/inducido químicamente , Colitis/enzimología , Colitis/microbiología , Colon/efectos de los fármacos , Colon/microbiología , Colon/patología , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Expresión Génica , Glucuronidasa/química , Glucuronidasa/genética , Glucuronidasa/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Humanos , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Triclosán/química , Triclosán/metabolismo , Triclosán/toxicidad
2.
Food Chem Toxicol ; 148: 111943, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33359324

RESUMEN

Previous studies have revealed that Selenium-enriched rice protein hydrolysates (SPHs) could alleviate Pb2+-induced apoptosis in RAW264.7 macrophages. The purpose of the current study was to detect the effect of different selenium (Se) species on immunotoxicity of the Pb2+-induced RAW264.7 macrophages and explore the potential immunomodulatory mechanism. Herein, SPHs, an isolated SPHs fraction (SPHs-2), selenomethionine (SeMet), selenite (SeIV) were used to investigate their inhibitory effect and the impacts on the expression of cytokines and related protein kinases in immunomodulatory pathways. The results showed that, compared with Pb2+-only group, Se-containing components significantly enhanced the cell viability and effectively decrease nitric oxide (NO) content in Pb2+-induced RAW264.7 cells. Furthermore, compared with other Se species, SPHs-2 markedly decreased the secretion levels of pro-inflammatory cytokines TNF-α, NF-κB, IL-1ß, MyD88, IL-6 and IL-8. Western blot results demonstrated that SPHs-2 effectively downregulated the expressions of IκB, IKKα, p38, and Erk1/2, and also successfully blocked the phosphorylation of these protein kinases. Our findings suggested that SPHs-2 effectively attenuate inflammatory response and inhibit the immunotoxicity of Pb2+ on RAW264.7 macrophages via regulating NF-κB/MAPK signaling pathways.


Asunto(s)
Plomo/toxicidad , Macrófagos/efectos de los fármacos , Compuestos de Organoselenio/farmacología , Hidrolisados de Proteína/farmacología , Ácido Selenioso/farmacología , Selenometionina/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Óxido Nítrico/metabolismo , Oryza/química , Células RAW 264.7
3.
Small ; 16(36): e2001858, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32519440

RESUMEN

The recent ban of titanium dioxide (TiO2 ) as a food additive (E171) in France intensified the controversy on safety of foodborne-TiO2 nanoparticles (NPs). This study determines the biological effects of TiO2 NPs and TiO2 (E171) in obese and non-obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO2 (E171, 112 nm) and TiO2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short-chain fatty acids. Both TiO2 (E171) and TiO2 NPs increase abundance of pro-inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO2 NPs cause stronger colonic inflammation than TiO2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non-obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.


Asunto(s)
Colon , Disbiosis , Microbioma Gastrointestinal , Nanopartículas del Metal , Proteoma , Titanio , Animales , Colon/efectos de los fármacos , Disbiosis/inducido químicamente , Contaminación de Alimentos , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación/inducido químicamente , Nanopartículas del Metal/toxicidad , Ratones , Ratones Obesos , Proteoma/efectos de los fármacos , Proteómica , Titanio/toxicidad
4.
J Sci Food Agric ; 99(15): 6731-6740, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31350863

RESUMEN

BACKGROUND: Common oil-in-water plant-based emulsions are allergenic and unstable to environmental stress, leading to increased consumer concerns about the food industry. To solve the problem of safety and instability, we investigated the influence of environmental stress on the stability of emulsions containing various rice protein hydrolysates, and compared the performance to whey protein, a common food emulsifier. RESULTS: Rice protein hydrolysates were obtained by enzymatic hydrolysis with different proteases (neutrase, trypsin and alcalase). We evaluated the stability of emulsions produced with different hydrolysates according to storage, pH, ionic strength and thermal processing. Trypsin hydrolysates formed emulsion as stable as emulsion containing whey protein against a range of environmental stress containing pH (pH 6 to 7), salt (< 150 mmol L-1 NaCl) and temperature (30-90 °C). Moreover, a higher partition coefficient of protein in emulsion showed that the trypsin hydrolysates were easy to adsorb at the oil-water droplet interface, indicating its higher stability. CONCLUSION: The results obtained in the present study suggest that trypsin hydrolysates could be utilized as natural emulsifiers to stabilize emulsion instead of traditional animal-based emulsifiers, opening many opportunities with respect to hypoallergenic emulsion systems in the food industry. © 2019 Society of Chemical Industry.


Asunto(s)
Metaloendopeptidasas/química , Oryza/química , Hidrolisados de Proteína/química , Subtilisinas/química , Tripsina/química , Biocatálisis , Emulsiones/química , Concentración de Iones de Hidrógeno , Concentración Osmolar
5.
Food Chem ; 275: 696-702, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30724251

RESUMEN

The RAW264.7 cell model was employed to screen immunomodulatory selenium-containing peptides from selenium-enriched rice protein hydrolysates (SPHs). Moreover, the selenium-containing peptides of high-activity protein hydrolysates were purified by Sephadex G-25, and identified by reversed phase ultra performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry. The results showed that 25 peptide sequences containing selenomethionine (SeMet) information above 90% of probability confidence were found in a fraction of alcalase hydrolysates. SeMDPGQQ and TSeMMM of 100% probability confidence were speculated as two novel selenium-containing peptide sequences. The artificially synthesized peptide TSeMMM was subsequently verified by an excellent immunomodulatory activity at a concentration of 80 µg/mL. In conclusion, the immunomodulatory activity of SPHs was correlated to SeMet sequence in the structure of selenium-containing peptides, and TSeMMM with a stronger immunomodulatory activity demonstrated potential as functional food additives for improving human health.


Asunto(s)
Oryza/metabolismo , Péptidos/análisis , Hidrolisados de Proteína/química , Selenio/química , Espectrometría de Masas en Tándem , Secuencia de Aminoácidos , Animales , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Factores Inmunológicos/análisis , Factores Inmunológicos/aislamiento & purificación , Factores Inmunológicos/farmacología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metaloendopeptidasas/metabolismo , Ratones , Óxido Nítrico/metabolismo , Oryza/química , Péptidos/aislamiento & purificación , Péptidos/farmacología , Células RAW 264.7 , Selenometionina/química , Sonicación
6.
Food Funct ; 8(10): 3553-3562, 2017 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-28880032

RESUMEN

Edible mushrooms have been considered as a good source of bioactive components with various health benefits. Our previous study demonstrated the identity of a novel protein from Pleurotus eryngii, namely PEP, and its anti-inflammatory activities. Herein, we further determined the inhibitory effects of PEP against colon cancer cells. PEP suppressed the proliferation of human and murine colon cancer HCT116 and MC38 cells in a dose and time-dependent fashion, while it showed no inhibitory effect on normal human colonic myofibroblasts CCD-18Co at the same concentrations tested. Moreover, PEP induced cell cycle arrest and led to extensive cellular apoptosis in colon cancer cells, which was associated with the downregulation of cell cycle-related signaling proteins, e.g. cyclin B, cyclin E and cdc-2, and the upregulation of apoptosis-related signaling proteins, e.g. p53 and c-PARP. The results from an in vivo study showed that PEP treatment significantly suppressed tumor development of allograft colon cancer cells in mice, and this inhibition was associated with the upregulation of p21, p53, caspase-3 and cleaved caspase-3. Overall, our results provided a basis for PEP as a promising preventive agent against colon cancer.


Asunto(s)
Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/fisiopatología , Proteínas de Plantas/administración & dosificación , Pleurotus/química , Verduras/química , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA