Aberrant gene expression during placental development may affect fetal growth and contribute to preeclampsia. The high‑temperature requirement A (HTRA) family of proteins are serine proteases that may serve in the quality control of misfolded or mislocalized proteins. Recently, the potential involvement of HTRA1 and HTRA4 in the normal development of the placenta and in the pathogenesis of preeclampsia has been reported. The present study collected placental tissues from patients with severe preeclampsia and gestational age‑matched control samples. The expression of HTRA1 and HTRA4 was analyzed using reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry. The human trophoblast line HTR‑8 was transfected with HTRA1 or HTRA4, and cell function was assessed. The present study also detected the expression of HTRA1 and HTRA4 in HTR‑8/SVneo transfected cells under hypoxia (1% O2) and further studied the effects of hypoxia on HTR‑8 cell migration. HTRA1 and HTRA4 were mainly localized to the cytoplasm of syncytiotrophoblasts. The expression levels of the two genes were elevated in the placental tissues of patients with severe preeclampsia. Finally, it was determined in vitro that ectopic expression of HTRA1 and HTRA4 significantly attenuated HTR‑8 cell migration, and elevated HTRA1 limited HTR‑8 cell growth. Under hypoxic conditions, the expression levels of HTRA1 and HTRA4 improved significantly. It was hypothesized that the aberrant expression of HTRA1 or HTRA4 may be involved in the onset of preeclampsia, and increased HTRA1 or HTRA4 expression may affect trophoblast functions.
Background To evaluate the impact of oral carbohydrate-rich (Ch-R) supplement taken 2 hours before an elective caesarean delivery (CD) on maternal and neonatal perioperative outcomes. Methods Ninety pregnant women undergoing elective CD were randomized into the Ch-R group, placebo group and fasting group equally. Participants’ blood was drawn at three time points, before intervention, immediately after and 1 day after the surgery to measure maternal and neonatal biochemical indices. Meanwhile women’s perioperative symptoms and signs were recorded. Results Eighty-eight pregnant women were finally included in the study. Women who had drunk Ch-R supplement had lower postoperative insulin level (β = − 3.50, 95% CI − 5.45 to − 1.56), as well as postoperative HOMA-IR index (β = − 0.74, 95% CI − 1.15 to − 0.34), compared with women who had fasted. Additionally, neonates of mothers who were allocated in the Ch-R group also had a higher glucose level, compared with neonates of mothers in the fasting group (β = 0.40, CI 0.17 to 0.62). Conclusion Oral Ch-R solution administered 2 hours before an elective CD may not only alleviate maternal postoperative insulin resistance, but also comfort women’s preoperative thirst and hunger, compared to fasting. Additionally, it may increase neonatal glucose level as well. Trial registration Chinese Clinical Trial Registry, ChiCTR2000033163. Data of Registration: 2020-5-22.
Background: Maternal gestational weight gain (GWG) influences not only on pregnancy outcome but also impacts on mothers' and children's long-term health. However, there is no consensus on recommendations of optimal GWG in Asians or the Chinese population.Methods: We performed a secondary analysis of the birth outcome of Chinese women who had joined the "Hyperglycemia and Adverse Pregnancy Outcome" study in Hong Kong and their children's cardiometabolic risk at 7-year of age. Optimal ranges of GWG were derived from models based on the probabilities of small for gestational age and large for gestational age (model 1), lean and fat infants (model 2) and the integration of model 1 and 2 (model 3), and were compared with that recommended by the Institute of Medicine (IOM) on children's cardiometabolic risk.Findings: GWG range derived from model 2 is associated with 8 cardiometabolic risk factors, while that from models 1 and 3 are associated with 1 and 7 of them respectively. Mothers whose GWG lie within the recommended range increases from 40.8% according to the IOM recommendation to 50.2% according to that derived from model 2.Interpretation: Optimal GWG derived from model 2 (i.e. 14.0-18.5 kg, 9.0-16.5 kg and 5.0-11.0 kg for underweight, normal weight and overweight Chinese women, respectively) appeared to be associated with the lowest cardiometabolic risk in the offspring.
Background Wogonin (5,7-dihydroxy-8-methoxyflavone), one of flavonoids isolated from the Scutellaria baicalensis, has been regarded as an anticancer candidate because of its maximal efficacy in cancer cells. This study aimed to explore the possible mechanism that wogonin uses to enhance the sensitivity of ovarian cancer cells to cisplatin chemotherapy. Material/Methods The growth inhibition rates of ovarian cancer cells SKOV3/DDP and C13* were assessed by Cell Counting Kit-8 (CCK-8) assay. The apoptosis was assessed under a fluorescence microscope following staining with Hoechst. We further analyzed the expression of Bcl-2, cleaved caspases-3, cleaved-PARP, and phospho-Akt by western blotting. Results In the present study, we found that wogonin reduced proliferation of ovarian cancer cells SKOV3, SKOV3/DDP, OV2008, and C13* in dose- and time-dependent manners and it sensitized cisplatin-induced cytotoxicity. Moreover, treatment with wogonin also increased cisplatin-resistant SKOV3/DDP and C13* cells to low dose cisplatin-induced cell apoptosis. Additionally, such treatment resulted in a significant decrease in phosphorylated Akt. Conclusions Wogonin could significantly increase the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin by downregulating the PI3K/Akt pathway.
BackgroundAccumulating studies have demonstrated that high-mobility group A2 (HMGA2), an oncofetal protein, plays a role in tumor development and progression. However, the molecular role of HMGA2 in ovarian carcinoma is yet to be established. MicroRNAs (miRNAs), a group of small noncoding RNAs, negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. The aim of this study was to investigate the potential involvement of a specific miRNA, miR-219-5p, in HMGA2-induced ovarian cancer.MethodsThe ovarian cancer cell line, SKOV3, was employed, and miR-219-5p and HMGA2 overexpression vectors constructed. The CCK-8 kit was used to determine cell proliferation and the Transwell® assay used to measure cell invasion and migration. RT-PCR and western blot analyses were applied to analyze the expression of miR-219-5p and HMGA2, and the luciferase reporter assay used to examine the interactions between miR-219-5p and HMGA2. Nude mice were employed to characterize in vivo tumor growth regulation.ResultsExpression of miR-219-5p led to suppression of proliferation, invasion and migration of the ovarian cancer cell line, SKOV3, by targeting HMGA2. The inhibitory effects of miR-219-5p were reversed upon overexpression of HMGA2. Data from the luciferase reporter assay showed that miR-219-5p downregulates HMGA2 via direct integration with its 3′-UTR. Consistent with in vitro findings, expression of miR-219-5p led to significant inhibition of tumor growth in vivo.ConclusionOur results collectively suggest that miR-219-5p inhibits tumor growth and metastasis by targeting HMGA2.
OBJECTIVE To compare the performance of diagnostic criteria for gestational diabetes mellitus (GDM) proposed by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) with those endorsed by the National Institute for Health and Care Excellence (NICE) in predicting adverse pregnancy outcomes. RESEARCH DESIGN AND METHODS We performed a secondary data analysis of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study participants in five study centers. Logistic regression analyses were performed, and Akaike information criterion were applied for the comparison of different statistical prediction models. We further analyzed the performance by four racial/ethnic subgroups, namely, Whites, Hispanics, Asians, and Blacks. RESULTS Among all, IADPSG criteria diagnosed 267 (4.1%) more women with GDM, but predicted primary caesarean section (CS) and large for gestational age (LGA) and neonatal adiposity better than did NICE criteria after adjustment for potential confounders. Among Whites, IADPSG criteria diagnosed 65 (2.5%) more subjects with GDM and predicted LGA and neonatal adiposity better, but predicted hypertensive disorders, primary CS and clinical neonatal hypoglycemia worse. Among Hispanics, the IADPSG criteria diagnosed 203 (12.1%) more with GDM but performed better in predicting hypertensive disorders, LGA, neonatal adiposity, and hyperinsulinemia. Among Asians, the IADPSG criteria diagnosed 34 (2.0%) fewer subjects with GDM but predicted hypertensive disorders better in the unadjusted model. In Blacks, IADPSG criteria diagnosed 34 (10.5%) more women with GDM. CONCLUSIONS IADPSG criteria appear to be more favorable than NICE for identification of adverse pregnancy outcomes among Hispanic and Asian women, while they are comparable to NICE among White women.
<p> </p> <p><strong>Objective: </strong>To compare the performance of diagnostic criteria for gestational diabetes mellitus (GDM) proposed by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) with those endorsed by the National Institute for Health and Care Excellence (NICE) in predicting adverse pregnancy outcomes.</p> <p><strong>Research Design and Methods:</strong> We performed a secondary data analysis on the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study participants in five study centers. Logistic regression analyses were performed and Akaike information criterion were applied for the comparison of different statistical prediction models. We further analyzed the performance by four ethnic subgroups, namely, Whites, Hispanics, Asians and Blacks.</p> <p><strong>Results:</strong> Among all, IADPSG criteria diagnosed 267 (4.1%) more women with GDM, but predicted primary caesarean section (CS), large for gestation (LGA) and neonatal adiposity better than did NICE criteria after adjustment for potential confounders. Among Whites, IADPSG criteria diagnosed 65 (2.5%) more subjects with GDM, and predicted LGA and neonatal adiposity better, but predicted hypertensive disorders, primary CS and clinical neonatal hypoglycemia worse. Among Hispanics, the IADPSG criteria diagnosed 203 (12.1%) more with GDM but performed better in predicting hypertensive disorders, LGA, neonatal adiposity and hyperinsulinemia. Among Asians, the IADPSG criteria diagnosed 34 (2.0%) fewer subjects with GDM but predicted hypertensive disorders better in the unadjusted model. In Blacks, IADPSG criteria diagnosed 34 (10.5%) more women with GDM.</p> <p><strong>Conclusion:</strong> IADPSG criteria appear to be more favorable than NICE for identification of adverse pregnancy outcomes among Hispanic and Asian women, while it is comparable to NICE among the Whites.</p> <p> </p>
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