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OBJECTIVES: The purpose of our research was to determine the expression of Cx26 and miR-2114-3p, and their effects on proliferation, migration, and invasion in ovarian cancer and their mechanisms. MATERIALS AND METHODS: Transcriptome sequencing was performed and differentially expressed Cx26 was screened. The mRNA and protein levels of Cx26 in EOC and normal ovarian tissues were verified. The relationship between Cx26 levels and prognostics was analyzed. Cx26 Lentiviral vectors were constructed to detect its effect on ovarian cancer. WB verified that PI3K/AKT pathway was the possible signal pathway regulated by Cx26. The interaction between miR-2114-3p and Cx26 was detected by double luciferase reporter assay and qrt-PCR. CCK8, clone formation, transwell, and flow cytometry assays were conducted in cells transfected miR-2114-3p plasmids. The vivo experiment investigated the effects of Cx26 on subcutaneous tumor growth, PI3K expression, proliferation proteins Ki67 and PCNA. RESULTS: Cx26 was up-regulated in EOC tissue and cell lines, and was associated with poor prognosis of ovarian cancer, while miR-2114-3p was down-regulated in EOC cell lines. Cx26 was a direct target of miR-2114-3p. Cx26 overexpression and miR-2114-3p inhibition promoted the growth, motility, invasiveness, and S phase arrest of EOC cells. Additionally, Cx26 could activated PI3K pathway whatever in vivo and in vitro. CONCLUSIONS: Dysregulation of Cx26 is critical in EOC patients. Manipulation of this mechanism may influence the survival of EOC patients. MiR-2114-3p regulates the tumor-promoting activity of Cx26 in EOC. By inhibiting the PI3K pathway or knocking down Cx26 effectively inhibits tumor growth in EOC cells and Nude mouse model.
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MicroRNAs , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Conexina 26 , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
Objective: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, which is increasing annually. GDM can cause serious harm to both the mother and the offspring. However, the clinical indicators that predict pregnancy outcomes with GDM remain limited. Methods: This study included 3,229 pregnancies. Inflammatory markers were defective in the mother's peripheral blood. Also, the Chi-square test, logistic regression analyses and Spearman rank correlation coefficient were performed to evaluate inflammatory markers with pregnancy outcomes. The association between inflammatory markers and pregnancy outcomes was analyzed. The optimal cut-off values of inflammatory markers were calculated. Results: Finally, 3,229 women were included. 1852 (57.36%) participants suffered good pregnancy outcomes. This study revealed that the maternal age, the baseline BMI (kg/m2), the times of parity, and the level of lymphocyte, SII and SIRI significantly increased in poor pregnancy outcomes groups. Additionally, inflammatory markers, such as white blood cells (WBC), neutrophils, monocytes, platelet counts, lymphocytes, systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were related to pregnancy outcomes. Furthermore, the results revealed that the SII level had the highest odd rates (OR) [OR = 6.957; 95% CI (5.715-8.468)], followed by SIRI level [OR = 2.948; 95% CI (2.382-3.649)], the WBC counts [OR = 1.930; 95% CI (0.901-2.960)], the lymphocyte counts [OR = 1.668; 95% CI (1.412-1.970)], and baseline BMI [OR = 1.050; 95% (1.021-1.080)]. Conclusion: This study presented that the baseline SII and SIRI levels can be valuable biochemical markers to predict the pregnancy outcome with GDM with non-invasive procedures. They can help identify high-risk pregnant women with GDM early, provide a personalized intervention in time, and enhance perinatal surveillance.
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AIMS: Ferroptosis, a novel mode of cell death characterized by lipid peroxidation and oxidative stress, plays an important role in the pathogenesis of preeclampsia (PE). The aim of this study is to determine the role of Nox2 in the ferroptosis of trophoblast cells, along with the underlying mechanisms. METHODS: The mRNA and protein levels of Nox2, STAT3, and GPX4 in placental tissues and trophoblast cells were respectively detected by qRT-PCR and western blot analysis. CCK8, transwell invasion and tube formation assays were used to evaluate the function of trophoblast cells. Ferroptosis was evaluated using flow cytometry and the lipid peroxidation assay. Glycolysis and mitochondrial respiration were investigated by detecting the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) using Seahorse extracellular flux technology. The t-test or one-way ANOVA was used for statistical analysis. KEY FINDINGS: Nox2 was up-regulated while STAT3 and GPX4 were down-regulated in PE placental tissues. Nox2 knockdown inhibited ferroptosis in trophoblast cells, which was shown by enhanced proliferation and invasion, decreased ROS and lipid peroxide levels, and reduced glycolysis and mitochondrial dysfunction. Nox2 negatively correlated with MVD in PE placentas, and Nox2 knockdown restored ferroptosis-inhibited tube formation. Nox2 could interact with STAT3. Inhibiting Nox2 restored ferroptosis-induced alterations in the mRNA and protein levels of STAT3 and GPX4. SIGNIFICANCE: Nox2 may trigger ferroptosis through the STAT3/GPX4 pathway, subsequently leading to regulation of mitochondrial respiration, transition of glycolysis, and inhibition of placental angiogenesis. Therefore, targeted inhibition of Nox2 is expected to become a new therapeutic target for PE.
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Ferroptose , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Linhagem Celular , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismo , Trofoblastos/metabolismoRESUMO
Aim: This study aimed to assess the predictive and diagnostic value of the risk of ovarian malignancy algorithm (ROMA) index for epithelial ovarian cancer (EOC) recurrence. Materials & methods: The clinical features and follow-up data of 159 EOC cases were studied. The ROMA index was calculated by serum CA125 and HE4 levels with menopausal status. Recurrence-free survival was evaluated for an end point. Results: The ROMA was strongly associated with clinical characteristics. The ROMA index above the cutoff value (34.71%) was significantly associated with recurrence-free survival. The ROMA index had a significantly higher sensitivity (90.59%) than CA125 (84.71%) and HE4 (80.80%) for recurrence diagnosis, and its optimal cutoff value was 17.07%. Conclusion: The primary ROMA index is a predictive factor in EOC recurrence and has better performance in the diagnosis of EOC recurrence.