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1.
Basic Clin Pharmacol Toxicol ; 128(5): 669-676, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33523585

RESUMO

Numerous documents have been stated that tropisetron, an antagonist of the 5-HT3 receptor and α7nAChR agonist, modulates immune responses. However, the mechanistic basis for this aspect of tropisetron action is largely unknown. Here, the immuno-modulatory effects of tropisetron are investigated, focusing on the possible molecular targets and the mechanisms. Aside from the well-characterized role in immune signalling, JAK2/STAT3, TLR2 and TLR4 are signal transducers linked to both immuno-modulatory actions of acetylcholine and serotonin. Therefore, we evaluated their involvement in the immunoregulatory effects of tropisetron. To test the hypothesis, we assessed the expression of pro-/anti-inflammatory cytokines including TNF-α, IL-1ß, IL-17 and IL-10 following tropisetron treatment in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) derived from healthy subjects. Tropisetron up-regulates the transcription of TLR2, TLR4, JAK2 and STAT3 genes. Tropisetron also increases the expression of target pro-inflammatory cytokines, although considerably suppresses the pro-inflammatory cytokines (IL-1ß, IL-17 and TNF-α) levels in media. Tropisetron notably promotes both IL-10 gene expression and secretion. These findings confirm the antiphlogistic properties of tropisetron. The present data also shed light on a new aspect of tropisetron immune-modulatory action that engaged TLR2, TLR4 and JAK2/STAT3 signalling cascades.


Assuntos
Anti-Inflamatórios/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Tropizetrona/farmacologia , Células Cultivadas , Voluntários Saudáveis , Humanos , Janus Quinase 2/metabolismo , Leucócitos Mononucleares/imunologia , Lipopolissacarídeos/imunologia , Cultura Primária de Células , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo
2.
Adv Biomed Res ; 3: 151, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25221754

RESUMO

BACKGROUND: The aerobic Actinomycetes are a large group of soil-indwelling bacteria that are distributed in world-wide. These Gram-positive bacteria are most commonly associated with opportunistic infections in both immunocompromised and immunocompetent hosts. MATERIALS AND METHODS: In this study, three phenotypic and deoxyribonucleic acid (DNA) extraction methods for isolation and identification of Nocardia genus were compared. Samples were taken in five different locations of Isfahan's suburb from hospitals area, parks, agricultural lands, gardens, arid lands with different soil temperature and pH. RESULTS: In this study, showed that slip-buried-method was better than two other phenotypic methods; 14 out of 70 soil samples (20%) were positive for Nocardia spp. DNA of positive samples were extracted with three techniques and DNA extraction by microwave technique was better than others. This technique was confirmed with observation of DNA bands on 1% agarose gel. CONCLUSIONS: These bacteria are important in immune deficient patients such as cancer patients, transplant recipients, tuberculosis; acquired immunodeficiency syndrome etc., Their affluence is unsteady in different zones of the world. In this study, among the three phenotypic methods for the isolation of Nocardia slip-buried method was better than other methods. Among DNA extraction techniques, DNA extraction by microwave method would be selective method for DNA extraction of Nocardia spp. compared with others techniques.

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