Effect of intrahepatic cholestasis of pregnancy on infantile food allergy: A retrospective longitudinal study cohort in Southwest China.

INTRODUCTION: Intrahepatic cholestasis of pregnancy has been consistently associated with a higher incidence of adverse pregnancy outcomes. Previous studies mainly focused on the effects of intrahepatic cholestasis of pregnancy on pregnant mothers and fetuses, and few studies reported the postpartum growth and development of fetuses in pregnant women with intrahepatic cholestasis of pregnancy. The aim of this study was to investigate impact of maternal serum total bile acid levels on maternal and neonatal outcomes as well as child growth and food allergy. MATERIAL AND METHODS: A retrospective longitudinal cohort investigation was carried out among 751 pregnant women with intrahepatic cholestasis of pregnancy at 30-32 weeks of gestation from the Longitudinal Intrahepatic Cholestasis of Pregnancy Study (LoICPS). Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected. RESULTS: In our cohort, the average maternal serum total bile acid level was 35.09±30.02 µmol/L, with 58.8% of mothers suffering from mild intrahepatic cholestasis of pregnancy and 29.2% suffering from severe intrahepatic cholestasis of pregnancy. Positive correlations were found between maternal serum total bile acid levels and twin pregnancy (beta-value: 11.55, 95% CI: 2.89 - 20.20. P = 0.009) and meconium stained amniotic fluid (beta-value: 14.64, 95% CI: 9.41 - 19.87. P < 0.001). In addition, the infants of mothers with severe intrahepatic cholestasis of pregnancy were more likely to be allergic to foods at 6 months. CONCLUSIONS: This study suggested that despite pregnant women with intrahepatic cholestasis of pregnancy taking ursodeoxycholic acid tablets and cesarean section before expected date of childbirth, the perinatal outcome of newborns partially improving, the incidence of infantile food allergy was still increased.

Nesfatin-1 Promotes Proliferation, Migration and Invasion of HTR-8/SVneo Trophoblast Cells and Inhibits Oxidative Stress via Activation of PI3K/AKT/mTOR and AKT/GSK3ß Pathway.

Preeclampsia (PE) is a leading cause of perinatal and maternal mortality. Considering that Nesfatin-1 was reported to be downregulated in serum of PE patients, we aimed to explore the functional role of Nesfatin-1 in trophoblast cells. Cell transfection was conducted to overexpress or inhibit Nesfatin-1, and its expression was measured by quantitative PCR. Cell proliferation, migration, and invasion abilities were determined employing CCK-8, flow cytometry, wound-healing, and transwell assays. Immunofluorescence assay was performed to detect E-cadherin and vimentin. ROS, MDA, and SOD levels were measured using their corresponding commercial kits. Western blot was used to identify the expression of vital kinases in PI3K/AKT/mTOR or GSK3ß pathway and invasion-related proteins in trophoblast cells. Nesfatin-1 knockdown significantly suppressed proliferation, migration, and invasion and increased cell arrest in G1 phase, as well as downregulated expressions of MMP2/9 in HTR-8/SVneo cells. Besides, Nesfatin-1 knockdown promoted the expression of E-cadherin and reduced the expression of vimentin. Additionally, the levels of ROS, MDA, and SOD were elevated upon Nesfatin-1 knockdown. On the contrary, Nesfatin-1 overexpression exerted the opposite effects. Nesfatin-1 promoted the activation of PI3K/AKT/mTOR or GSK3ß pathway, blocking of which reversed the promotive effects on trophoblast invasion and the inhibitory effects on oxidative stress of Nesfatin-1 in HTR-8/SVneo cells. In short, this study revealed that Nesfatin-1 promoted trophoblast cell proliferation, migration, invasion, and EMT and suppressed oxidative stress by activating PI3K/AKT/mTOR and AKT/GSK3ß signaling pathway, laying the foundation for the development of therapeutic strategy for PE by targeting Nesfatin-1.

A novel risk score system for assessment of ovarian cancer based on co-expression network analysis and expression level of five lncRNAs.

BACKGROUND: Ovarian cancer (OC) is the most deadly gynaecological cancer, contributing significantly to female cancer-related deaths worldwide. Improving the outlook for OC patients depends on the identification of more reliable prognostic biomarkers for early diagnosis and survival prediction. The various roles of long non-coding RNAs (lncRNAs) in OC have attracted increasing attention. This study aimed to identify a lncRNA-based signature for survival prediction in OC patients. METHODS: RNA expression data and clinical information from a large number of OC patients were downloaded from a public database. These data were regarded as a training set to construct a weighed gene co-expression network analysis (WGCNA) network, mine stable modules, and screen differentially expressed lncRNAs. The prognostic lncRNAs were screened using univariate Cox regression analysis and the optimal prognosis lncRNA combination was screened using a Cox-PH model. The finalised lncRNA combination was used to construct the risk score system, which was validated and assessed for effectiveness using other independent datasets. Further functional pathway enrichment was performed using gene set enrichment analysis (GSEA). RESULTS: A co-expression network was constructed and four stable modules with OC-related biological functions were obtained. A total of 19 lncRNAs significantly related to prognosis of ovarian cancer were obtained using univariate Cox regression analysis, and the 5 prognostic signature lncRNAs GAS5, HCP5, PART1, SNHG11, and SNHG5 were used to establish a risk assessment system. The reliability of the prognostic scoring system was further confirmed using validation sets, which indicated that the risk assessment system could be used as an independent prognostic factor. Pathway enrichment analysis revealed that the network modules related to the above five prognostic genes were significantly associated with cell local adhesion, cancer signaling pathways, JAK-STAT signalling, and endogenous cell receptor interaction. CONCLUSIONS: The risk score system established in this study could provide a novel reliable method to identify individuals at high risk of OC. In addition, the five prognostic lncRNAs identified here are promising potential prognostic biomarkers that could help to elucidate the pathogenesis of OC.