Childbirth as Fault Lines: Justifications in Physician-Patient Interactions About Postnatal Rehabilitation.

Research on justifications has shown their significance in advice-giving, decision-making and children disputes. However, the majority of studies gloss over practical functions of justifications in patient-physician interactions as they are often expected and pursued by patients and in turn, are adopted by physicians to support their stance and authority. This study, through conversation analysis (CA), aims to explore a) what are pragmatic functions of justifications in patient-physician interaction? b) how and when do physicians unfold their justifications for treatment recommendations? c) how do physicians deal with different responses based on their epistemic and deontic domains?. A total of 32 video-recordings between postpartum women and physicians are collected and studied. Four pragmatic functions of justifications drawn upon by physicians are explored: justifications as face-saving, reassurance, risk discussion and clarification-seeking. Despite physicians' attempts to justify their positions as less challenged by patients, this is not the entire picture as they demonstrate their desire to resolve patients' concerns and coordinate their viewpoints to achieve the best practice that facilitates patients' well-being.

Leptin Promotes HTR-8/SVneo Cell Invasion via the Crosstalk between MTA1/WNT and PI3K/AKT Pathways.

The process of placental invasion is essential for a successful pregnancy. Leptin is involved in trophoblast invasiveness, and its dysregulation is connected with a series of diseases, including preeclampsia. However, the knowledge of the precise mechanisms in leptin-induced trophoblast invasiveness is still limited. According to the present research, transwell assay suggested that leptin is a dose- and time-dependent regulator in inducing HTR-8/SVneo cell invasion. Western blot analysis and immunofluorescence staining revealed that leptin-induced MMP9 expression is essential in the invasion process of HTR-8/SVneo cells. Mechanistically, we demonstrated that leptin activated ß-catenin via the crosstalk between the MTA1/WNT and PI3K/AKT pathways. Besides, we showed that downregulating the key molecules in the signaling pathways by siRNA can inhibit leptin-induced MMP9 expression and further suppress invasion of HTR-8/SVneo cells. In conclusion, our study revealed a new regulatory mechanism of leptin-induced HTR-8/SVneo cell invasiveness and will provide novel insights into the causes and potential therapeutic targets for diseases related to dysregulation of trophoblast invasion in the future.

Hypoxia induced-disruption of lncRNA TUG1/PRC2 interaction impairs human trophoblast invasion through epigenetically activating Nodal/ALK7 signalling.

Inadequate trophoblastic invasion is considered as one of hallmarks of preeclampsia (PE), which is characterized by newly onset of hypertension (>140/90 mmHg) and proteinuria (>300 mg in a 24-h urine) after 20 weeks of gestation. Accumulating evidence has indicated that long noncoding RNAs are aberrantly expressed in PE, whereas detailed mechanisms are unknown. In the present study, we showed that lncRNA Taurine upregulated 1 (TUG1) were downregulated in preeclamptic placenta and in HTR8/SVneo cells under hypoxic conditions, together with reduced enhancer of zeste homolog2 (EZH2) and embryonic ectoderm development (EED) expression, major components of polycomb repressive complex 2 (PRC2), as well as activation of Nodal/ALK7 signalling pathway. Mechanistically, we found that TUG1 bound to PRC2 (EZH2/EED) in HTR8/SVneo cells and weakened TUG1/PRC2 interplay was correlated with upregulation of Nodal expression via decreasing H3K27me3 mark at the promoter region of Nodal gene under hypoxic conditions. And activation of Nodal signalling prohibited trophoblast invasion via reducing MMP2 levels. Overexpression of TUG1 or EZH2 significantly attenuated hypoxia-induced reduction of trophoblastic invasiveness via negative modulating Nodal/ALK7 signalling and rescuing expression of its downstream target MMP2. These investigations might provide some evidence for novel mechanisms responsible for inadequate trophoblastic invasion and might shed some light on identifying future therapeutic targets for PE.

HDAC4 Knockdown Induces Preeclampsia Cell Autophagy and Apoptosis by miR-29b.

Preeclampsia (PE) is one of the main causes of maternal death and perinatal morbidity and mortality. Considering that histone deacetylase 4 (HDAC4) activity could relate to trophoblast cell motility and be antagonized by miR-29b, the aim of the present study was to investigate the ability of HDAC4 to regulate placental trophoblast cells by miR-29b. We assessed the cytological changes of PE patients, and the expression and cellular localization of HDAC4 and LC3 by histological analysis, immunohistochemistry, western blot assay, and immunofluorescence staining assay. We observed the effect of hypoxia on HDAC4, the correction of HDAC4/miR-29b, and the effects of HDAC4/miR-29b on HTR8 cells by dual-luciferase, quantitative real-time PCR, western blot assay, and flow cytometry assay. Here, we first found that HDAC4 was lowly expressed in PE tissues, while LC3 was highly expressed. In addition, the expression of HDAC4 was inhibited by hypoxia in HTR8 cells. Furthermore, our data showed that HDAC4 activity could be antagonized by miR-29b. We highlighted that miR-29b specifically targeted HDAC4 in trophoblast cells and both molecules were involved in a functional loop. Altogether, our findings demonstrated that silencing of HDAC4 could trigger cell autophagy and apoptosis directly by miR-29b in placental trophoblast cells of PE.