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1.
Int J Nanomedicine ; 14: 2219-2232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30992664

RESUMO

PURPOSE: The use of bacteriophages represents a valid alternative to conventional antimicrobial treatments, overcoming the widespread bacterial antibiotic resistance phenomenon. In this work, we evaluated whether biomimetic hydroxyapatite (HA) nanocrystals are able to enhance some properties of bacteriophages. The final goal of this study was to demonstrate that biomimetic HA nanocrystals can be used for bacteriophage delivery in the context of bacterial infections, and contribute - at the same time - to enhance some of the biological properties of the same bacteriophages such as stability, preservation, antimicrobial activity, and so on. MATERIALS AND METHODS: Phage isolation and characterization were carried out by using Mitomycin C and following double-layer agar technique. The biomimetic HA water suspension was synthesized in order to obtain nanocrystals with plate-like morphology and nanometric dimensions. The interaction of phages with the HA was investigated by dynamic light scattering and Zeta potential analyses. The cytotoxicity and intracellular killing activities of the phage-HA complex were evaluated in human hepatocellular carcinoma HepG2 cells. The bacterial inhibition capacity of the complex was assessed on chicken minced meat samples infected with Salmonella Rissen. RESULTS: Our data highlighted that the biomimetic HA nanocrystal-bacteriophage complex was more stable and more effective than phages alone in all tested experimental conditions. CONCLUSION: Our results evidenced the important contribution of biomimetic HA nanocrystals: they act as an excellent carrier for bacteriophage delivery and enhance its biological characteristics. This study confirmed the significant role of the mineral HA when it is complexed with biological entities like bacteriophages, as it has been shown for molecules such as lactoferrin.


Assuntos
Materiais Biomiméticos/química , Durapatita/química , Nanopartículas/química , Fagos de Salmonella/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Galinhas , Endocitose/efeitos dos fármacos , Fluorescência , Genoma Bacteriano , Células Hep G2 , Humanos , Nanopartículas/ultraestrutura , Filogenia , Pós , Fagos de Salmonella/genética , Difração de Raios X
2.
Sci Rep ; 7(1): 13446, 2017 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-29044138

RESUMO

Clothianidin is a widely used neonicotinoid insecticide, which is a potent agonist of the nicotinic acetylcholine receptor in insects. This neurotoxic compound has a negative impact on insect immunity, as it down-regulates the activation of the transcription factor NF-κB. Given the evolutionary conserved role of NF-κB in the modulation of the immune response in the animal kingdom, here we want to assess any effect of Clothianidin on vertebrate defense barriers. In presence of this neonicotinoid insecticide, a pro-inflammatory challenge with LPS on the human monocytic cell line THP-1 results both in a reduced production of the cytokine TNF-α and in a down-regulation of a reporter gene under control of NF-κB promoter. This finding is corroborated by a significant impact of Clothianidin on the transcription levels of different immune genes, characterized by a core disruption of TRAF4 and TRAF6 that negatively influences NF-κB signaling. Moreover, exposure to Clothianidin concurrently induces a remarkable up-regulation of NGFR, which supports the occurrence of functional ties between the immune and nervous systems. These results suggest a potential risk of immunotoxicity that neonicotinoids may have on vertebrates, which needs to be carefully assessed at the organism level.


Assuntos
Guanidinas/efeitos adversos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Inseticidas/efeitos adversos , Neonicotinoides/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Tiazóis/efeitos adversos , Biomarcadores , Linhagem Celular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema Imunitário/imunologia , NF-kappa B/genética , NF-kappa B/metabolismo , Transcriptoma , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
3.
Nat Prod Res ; 31(18): 2119-2125, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28105862

RESUMO

Mushrooms produce a wide range of bioactive polysaccharides, different from each other in chemical structure and biological effects. In the last years, the idea to develop functional foods or drugs containing fungal polysaccharides is attracting great attention. Fruiting bodies of Basidiomycetes Ganoderma lucidum are commonly used in Oriental medicine to treat several disorders. G. lucidum polysaccharides - mainly ß-glucans and heteroglycans - have numerous biological properties such as antitumour and immunomodulatory activities. This report shows, by gene expression analyses and bioenergetic assays, immunomodulatory properties and capacity to improve glucose metabolism of a water-soluble heteroglycan extracted from mycelium of an Italian isolate of G. lucidum. The findings suggest the use of the heteroglycan as probiotic or ingredient in functional foods, being easy to produce and disperse in a food matrix thanks to its water-solubility. Heteroglycan could exert protective effects in pro-inflammatory conditions and benefits for people characterised by suppressed immune response.


Assuntos
Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Glucanos/farmacologia , Fatores Imunológicos/farmacologia , Reishi/química , Linhagem Celular , Citocinas/genética , Avaliação Pré-Clínica de Medicamentos/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucanos/química , Glucose/metabolismo , Humanos , Fatores Imunológicos/química , Itália , Espectroscopia de Ressonância Magnética , Medicina Tradicional do Leste Asiático , Micélio/química , Solubilidade , Água
4.
FEBS Lett ; 590(14): 2127-37, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27296467

RESUMO

The genes MyD88 and TIRAP encode the adaptor proteins MyD88 and TIRAP. TIRAP plays the crucial role of activating the MyD88-dependent pathway, which in turn controls the immune response (innate and adaptive) to Helicobacter pylori. We looked for an association of MyD88 and TIRAP with H. pylori infection. Cases and controls were genotyped at the polymorphic sites MyD88 rs6853 and TIRAP rs8177374 by real-time PCR. When the genes were analyzed separately, only TIRAP was associated with infection. When the genes were analyzed concurrently, certain combinations of MyD88 and TIRAP protected the host against H. pylori colonization more efficiently than could be done by TIRAP alone.


Assuntos
Epistasia Genética/imunologia , Infecções por Helicobacter , Helicobacter pylori/imunologia , Glicoproteínas de Membrana , Fator 88 de Diferenciação Mieloide , Polimorfismo Genético/imunologia , Receptores de Interleucina-1 , Adulto , Feminino , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/imunologia
5.
Int J Nanomedicine ; 9: 1175-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24623976

RESUMO

The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Lactoferrina/química , Lactoferrina/farmacologia , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bovinos , Linhagem Celular Tumoral , Durapatita/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Testes de Sensibilidade Microbiana , Nanocompostos/química , Nanomedicina , Nanopartículas/ultraestrutura
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