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1.
Biology (Basel) ; 13(6)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38927262

RESUMO

Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT1R blockade has anti-inflammatory effects. The use of an AT1 receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT1 receptor gene silencing on the modulation of cytokines (e.g., IL-1ß, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. MATERIALS AND METHODS: We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT1R, NF-κB, and cytokines (IL-1ß, TNF-α, and IL-10) were measured by RT-qPCR. RESULTS: We observed that silencing of the AT1 receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1ß and TNF-α), NF-κB, and PPAR-γ. CONCLUSIONS: We conclude that AT1R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1ß via NF-κB in macrophages and having high blood pressure decrease.

2.
Hepatol Commun ; 6(8): 2000-2010, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35438253

RESUMO

Patients with pre-existing liver diseases are considered to have an increased risk of morbidity and mortality from any type of infection, including viruses. The aim of this work was to explore the implications of metabolic dysfunction-associated fatty liver disease (MAFLD) and nonalcoholic fatty liver disease (NAFLD) definitions in coronavirus disease 2019 (COVID-19) and to study the interaction between advanced fibrosis (AF) and each of these diseases in the death and intubation of patients hospitalized with COVID-19. We performed a retrospective study with 359 patients hospitalized with confirmed COVID-19 infection in a tertiary referral hospital who were admitted between April and June 2020. A multivariate Cox model was performed regarding the interaction of AF with MAFLD and NAFLD in the mortality and intubation of patients with COVID-19. The death rate was statistically significantly higher in the MAFLD group compared to the control group (55% vs. 38.3%, p = 0.02). No significant difference was seen in the death rate between the NAFLD and control group. The MAFLD (44.09% vs. 20%, p = 0.001) and NAFLD (40.51% vs. 20%, p = 0.01) groups had statistically significantly higher intubation rates than the control group. A statistically significant interaction between NAFLD and AF was associated with an increase in mortality (p = 0.01), while a statistically significant interaction between MAFLD and AF was associated with an increased risk of mortality (p = 0.006) and intubation (p = 0.049). In the case of patients hospitalized with COVID-19, our results indicate that the death rate was higher in the MAFLD group but not the NAFLD group compared to that in the control group. The intubation rates were higher in the NAFLD and MAFLD groups compared to rates in the control group, suggesting that both could be associated with COVID-19 severity. In addition, we found interactions between AF with MAFLD and NAFLD.


Assuntos
COVID-19 , Hepatopatia Gordurosa não Alcoólica , Fibrose , Humanos , Intubação Intratraqueal , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Retrospectivos , Fatores de Risco
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