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1.
Mediators Inflamm ; 2022: 4250621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664920

RESUMO

Preeclampsia (PE) is a common pregnancy-related syndrome characterized by chronic immune activation. This study is aimed at exploring the role of miR-155 in the inflammatory pathogenesis of PE. Placental tissues and peripheral blood were collected from all subjects. BSP detection analysis was performed to evaluate miR-155 methylation levels. ELISA was performed to measure the levels of inflammatory cytokines and MMP2 in serum samples and cellular supernatants. HTR-8/SVneo and JEG-3 cells were transfected with miR-155 mimic and the inhibitor to establish the overexpressed miR-155 and silenced miR-155 cell models, respectively. Treatment with 5-Aza was performed to alter the DNA methylation level of miR-155. The PE rat model was established after subcutaneous injection of NG-nitro-L-arginine methyl ester. The CCK-8 assay, TUNEL staining, and Transwell assay were performed. Reverse transcription-quantitative PCR, Western blot analysis, and immunohistochemical assay were used to analyze related gene expression levels. The luciferase reporter assay was used to investigate the direct interaction between FOXO3 and miR-155. Results showed that miR-155 was remarkably upregulated and inversely correlated with the promoter methylation level in the placental tissue from PE patients. The in vitro experiments indicated that miR-155 decreased viability, migration, and invasion, but increased apoptosis in trophoblast cells. FOXO3 was confirmed as the target of miR-155. Transfection of the miR-155 inhibitor suppressed inflammation and oxidative stress, but elevated proliferation, migration, and invasion of trophoblast cells, which were abolished by 5-Aza treatment or cotransfection with si-FOXO3. In summary, our data suggested that methylation-mediated silencing of miR-155 can inhibit the apoptosis, inflammation, and oxidative stress of trophoblast cells by upregulating FOXO3.


Assuntos
MicroRNAs , Pré-Eclâmpsia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Humanos , Inflamação/metabolismo , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Ratos , Trofoblastos/metabolismo
2.
Ginekol Pol ; 93(12): 987-992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35072242

RESUMO

OBJECTIVES: Investigating the expression levels of plasma protein Z (PZ) and protein Z-dependent protease inhibitor (ZPI) in fetal growth restriction (FGR) and to explore their diagnostic value in FGR. MATERIAL AND METHODS: In this study, the number of pregnant women with FGR, healthy pregnant women (Healthy Control, HC), and childbearing-age women without pregnancy (Blank Control, BC) is 79, 79, and 60, respectively; their plasma PZ and ZPI levels in each group are determined by ELISAs. Then, the correlations between these indices and FGR were assessed using Spearman analysis. Moreover, these indices' diagnostic values for FGR are evaluated using the receiver operating characteristics (ROC) curves. RESULTS: The plasma levels of PZ and ZPI are significantly decreased in the HC and FGR groups compared against the BC group (P < 0.001), whilst the levels of PZ and ZPI in the FGR groups are lower than those in the HC group (P < 0.01) notably. PZ plasma concentration has positive relationship with ZPI concentrations in the HC and FGR groups. The combination of PZ and ZPI, with the Area under the Curve (AUC) 0.92 (95% CI = 0.88-0.96), the sensitivity 0.82, and the specificity 0.88, outperforms everyone. CONCLUSIONS: Plasma PZ and ZPI are significantly decreased in pregnant women with FGR, which can be used for pregnant women's FGR screening.


Assuntos
Inibidores de Proteases , Serpinas , Feminino , Humanos , Gravidez , Proteínas Sanguíneas , Retardo do Crescimento Fetal/diagnóstico , Inibidores de Proteases/metabolismo
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