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1.
Toxicology ; 506: 153872, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38924947

RESUMO

N,N-Dimethylformamide (DMF) is a well-documented occupational hazardous material, which can induce occupational liver injury. The current study was designed to investigate whether ethanol consumption can affect DMF-induced hepatotoxicity and the potential underlying mechanisms involved. We found that a single dose of ethanol (1.25, 2.5, or 5 g/kg bw by gavage) significantly repressed the increase in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and alleviated the liver histopathological changes in mice challenged with 3 g/kg DMF. In contrast, long-term moderate drinking (2.5 g/kg bw) significantly aggravated the repeated DMF (0.7 g/kg bw) exposure-induced increase in the serum ALT and AST activities. Mechanistically, acute ethanol consumption suppressed DMF-induced activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome, while long-term moderate ethanol consumption promoted hepatocyte apoptosis in the mouse liver. Notably, cytochrome P4502E1 (CYP2E1) protein level and activity in mouse livers were not significantly affected by ethanol per se in the two models. These results confirm that regular drinking can increase the risk of DMF-induced hepatotoxicity, and suggest that DMF-handling workers should avoid consuming ethanol to reduce the risk of DMF-indued liver injury.


Assuntos
Consumo de Bebidas Alcoólicas , Doença Hepática Induzida por Substâncias e Drogas , Citocromo P-450 CYP2E1 , Dimetilformamida , Etanol , Fígado , Animais , Dimetilformamida/toxicidade , Etanol/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Camundongos , Masculino , Citocromo P-450 CYP2E1/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Apoptose/efeitos dos fármacos , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Relação Dose-Resposta a Droga , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Camundongos Endogâmicos C57BL
2.
Front Microbiol ; 15: 1344162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486698

RESUMO

Objective: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). The purpose of this study was to explore the relationship between the number of natural killer (NK) cells and adaptive immune status, and disease severity in TBM patients. Methods: We conducted a retrospective study on 244 TB patients and 146 healthy control subjects in the 8th Medical Center of the PLA General Hospital from March 2018 and August 2023. Results: The absolute count of NK cells in the peripheral blood of TBM patients was significantly lower than that in normal controls (NC), latent tuberculosis infection (LTBI), and non-severe TB (NSTB) patients (p < 0.05). The proportion of TBM patients (48.7%) with a lower absolute count of NK cells than the normal reference value was significantly higher than that in NC (5.2%) and LTBI groups (4.0%) (p < 0.05), and slightly higher than that in NSTB group (36.0%) (p > 0.05). The absolute counts of lymphocyte subsets in TBM combined with other active TB group, etiology (+) group, IGRA (-) group, and antibody (+) group were lower than that in simple TBM group, etiology (-) group, IGRA (+) group, and antibody (-) group, respectively. The CD3+ T, NK, and B cells in BMRC-stage III TBM patients were significantly lower than those in stage I and stage II patients (p < 0.05). The counts of CD3+ T, CD4+ T, and B cells in the etiology (+) group were significantly lower than those in the etiology (-) group (p < 0.05). Conclusion: The absolute counts of lymphocyte subsets in the peripheral blood of TBM patients were significantly decreased, especially in NK cells. The reduction of these immune cells was closely related to the disease severity and had a certain correlation with cellular and humoral immune responses. This study helps to better understand the immune mechanism of TBM and provides reliable indicators for evaluating the immune status of TBM patients in clinical practice.

3.
J Org Chem ; 89(6): 4134-4144, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394632

RESUMO

Base-catalyzed diastereodivergent and regioselective domino processes of triketone enones with arylacetaldehydes for the synthesis of tetrahydrofuro[2,3-b]furans with four consecutive stereocenters are reported. Good yields and diastereoselectivities are obtained when DBU is employed as a catalyst; in contrast, Et3N delivers a different diastereomer in excellent diastereoselectivity. This work offers many advantages, including switchable diastereoselectivity, cheap base catalysts, and a simple operation.

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