Maternal decidua plays a critical role in implantation and placentation. Impaired decidualization causes failed intravascular trophoblast invasion and inadequate placentation and then increases the risk of preeclampsia (PE). RNA sequencing (RNA-Seq) has achieved great advances in the characterization and quantification of transcriptomes; is a powerful tool for new transcript discovery, genome annotation, and expression profiling. In the present study, we conducted a RNA-Seq analysis to compare gene expression between decidua of PE (n ¼ 3, early-onset severe PE, EOSPE; n ¼ 3, late-onset severe PE, LOSPE) and normal pregnancies (n ¼ 3). We revealed that decidual gene transcription profile was altered in severe PE and identified 293 key PE-related genes involved in 19 differentially regulated pathways relevant for the pathogenesis of PE, among which ENO2, PGK1, and HK2 involved in glycolysis/gluconeogenesis and HIF-1 signaling pathway which are all highly related with tumorigenesis and are significantly upregulated in cancer cells were severely inhibited in the decidua of PE. Moreover, we identified 22 core regulatory genes, including the newly identified pseudogenes BNIP3P1, HK2P1, and PGK1P1 that encode long non-coding RNA (lncRNA); interestingly, BNIP3/BNIP3P1, HK2/HK2P1, and PGK1/PGK1P1 appear in pairs in core genes. Subsequent analyses using quantitative PCR validated a portion of these results. This study may provide further insight into the mechanisms of PE and function as preventive, predictive, and therapeutic measures. Future functional studies are needed in order to accomplish a greater understanding of the mechanisms involved.

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Notch signaling was evolutionarily conserved and critical for cell-fate determination, differentiation and many other biological processes. Growing evidences suggested that Notch signaling pathway played an important role in the mammalian placental development. All of the mammalian Notch family proteins had been identified in human placenta except Delta-like 3, which appeared to affect the axial skeletal system. However the molecular mechanisms that regulated the Notch signaling pathway remained largely unknown in human placenta. Therefore, additional research was needed to investigate expression pattern of Notch family members and the mechanisms for activation of Notch signaling pathway in human placenta, which might help elucidate the roles of Notch signaling pathway in human placentation. This review would focus on the roles of Notch receptors and ligands in the human placental trophoblasts function and placental angiogenesis. It might hopefully provide perspectives for future research about human placentation of pregnancy complicated by preeclampsia and other placenta associated diseases.

Objectives: This study is aimed to identify the expression of Notch family proteins in placentas from patients with early-onset severe preeclampsia. Study Design: The expression of Notch family proteins in placentas was investigated by immunohistochemistry, Western blotting, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: The profile of distribution of all Notch family proteins in placentas from patients with early-onset severe preeclampsia is similar to that in normal placentas. All Notch family proteins are expressed in placental trophoblasts. Moreover, Notch1 and Jagged1 (Jag1) are detected in placental endothelial cells. Real-time RT-PCR showed that messenger RNA levels of Notch2 and Delta-like4 (Dll4) in placentas from patients with early-onset severe preeclampsia are lower than that of normal placentas. Western blotting showed a significant increase in Notch3 expression and a significant decrease in Notch2 expression in placentas from patients with early-onset severe preeclampsia relative to those in normal placentas. Conclusion: The results suggest that Notch2 and Notch3 may play some roles in the pathogenesis of preeclampsia.

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Background: To assess the feasibility and perioperative outcomes of single-port (SP) and multi-port (MP) approaches for video-assisted thoracoscopic surgery (VATS) lobectomy and anatomical segmentectomy.Methods: Retrospective data from 458 patients who received VATS lobectomy or anatomical segmentectomy at Shanghai Chest Hospital, Korea University Guro Hospital, Affiliated Hospital of National Taiwan University, University of Hong Kong Queen Mary Hospital and Shenzhen Hospital were collected.Patients were divided into SP group and MP group according to the surgical approach. Perioperative factors such as operation time, blood loss during surgery, conversion rate, the number and stations of lymph nodes harvested, postoperative chest tube drainage time, postoperative hospitalization time, perioperative morbidity and mortality, and pain scores during the first 3 days after surgery were compared between the two groups.Results: There were no differences in the number (P=0.278) and stations (P=0.564) of lymph nodes harvested, postoperative morbidity (P=0.414) or mortality(P=0.246), and pain score on the third day (P=0.630) after surgery between the two groups. The SP group had a longer operation time (P=0.042) and greater intraoperative blood loss (P<0.001), but the conversion rate was even higher in the MP group (P=0.018).Patients in the SP group had shorter chest tube removal time (P=0.012) and postoperative hospitalization time (P=0.005). Pain scores were lower on the first (P=0.014) and second (P=0.006) day after surgery in the SP group.Conclusions: SP VATS lobectomy and anatomical segmentectomy is technologically more demanding than MP VATS. It can be safe and feasible in the hands of experienced surgeons, with comparable preoperative outcomes to MP VATS, but less pain in the early postoperative period.

Introduction: Non-small cell lung cancer (NSCLC) is a deadly cancer type worldwide and the main sub-type of lung cancer. Cancer susceptibility candidate-9 (CASC9) was reported to be a key player in cancer progression. However, its function and underlying mechanism in NSCLC remain unclear. Materials and Methods: Expression level of CASC9 in NSCLC tissues and cells was measured with RT-qPCR. Biological roles of CASC9 in NSCLC were analyzed with a series of in vitro experiments. Potential mechanisms of CASC9 in NSCLC were analyzed by predicting and validating the possible targets of CASC9 in NSCLC. Results: In this study, we found CASC9 expression was upregulated in NSCLC tissues and cell lines. High CASC9 expression was identified as a predictor for poorer overall survival of NSCLC patients. Furthermore, functional assays showed CASC9 knockdown suppressed NSCLC cell proliferation, migration, and invasion, while CASC9 overexpression caused opposite effects. We also found microRNA-335-3p (miR-335-3p) could act as a target of CASC9 in NSCLC and the inhibition effect of CASC9 knockdown on NSCLC progression required the activity of miR-335-3p. In addition, we identified S100 calcium-binding protein A14 (S100A14) acts as a target of miR-335-3p. Discussion: Taken together, our study suggested CASC9 could promote NSCLC progression via miR-335-3p/S100A14 axis. The CASC9/miR-335-3p/S100A14 regulatory triplets identified in this work might provide new therapeutic strategies for NSCLC treatment.

The underlying mechanism about rhythms and epigenetics leading to aberrant trophoblast migration and invasion in recurrent spontaneous abortion (RSA) remains unknown. Brain and muscle ARNT-like protein 1 (BMAL1) is considered as a crucial role in fertility, and polymorphism of BMAL1 gene has been reported to be associated with risk of miscarriage. However, the functional role of BMAL1 in RSA is not fully understood. Previous study shows the descended expression of DNA 5′-cytosine-methyltransferases 1 (DNMT1) in the villous of early pregnancy loss. Thus, understanding of the regulation of DNMT1 expression may be of significance for the elucidation of the process of RSA. Using HTR-8/SVneo and JEG-3 cell lines, we certified the induction of specificity protein 1 (SP1) to DNMT1 and DAB2 interaction protein (DAB2IP), respectively, both of which further activated matrix metallo-proteinase 2/9 (MMP2/9), bringing out changes in trophoblast migration and invasion. Notably, BMAL1 functioned as a positive upstream factor of SP1 only in HTR-8/SVneo cells but not in JEG-3 cells, inducing SP1-DNMT1/DAB2IP pathway and facilitating migration and invasion of trophoblasts. In addition, progesterone might restore the down-regulation of BMAL1 and downstream pathway in a dose-dependent manner. Last but not least, the decreased abundance of BMAL1 was correlated positively with that of SP1, DNMT1, DAB2IP, MMP2 and MMP9 in human villous specimens of RSA. Our results demonstrate that the induction of BMAL1 to SP1 contributes to the expression of DNMT1 and DAB2IP, respectively, activating trophoblast migration and invasion. The deregulation of the BMAL1-mediated pathway in RSA can be rescued by progesterone.