Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). Yes-associated protein (YAP) is also found over-expressed in HCC and has been identified as a key effector molecule in Hippo pathway, which could control the organ size in animals through the regulation of cell proliferation and apoptosis and plays an important role in the development of malignant tumors. Studies have reported that GPC3 and YAP might collaborate to regulate the development of HCC. To elucidate the role of GPC3 in the development of HCC and its relationship with YAP, siRNA technique was employed to knock down GPC3 in Huh7 HCC cells. Moreover, recombinant human YAP-1 was used to examine the effects of GPC3 on Huh7 cells. The results of flow cytometric analysis and Annexin-V-FLUOS apoptosis assay showed that knockdown of GPC3-induced apoptosis in Huh7 cells, resulting in inhibition of cell proliferation as examined by EdU incorporation assay, migration, and invasion. GPC3 knockdown also suppressed the expression of YAP in mRNA and protein levels, as examined by fluorescence quantitative PCR and Western blot analysis. Moreover, addition of recombinant human YAP-1 effectively rescued the cells from apoptosis triggered by GPC3 knockdown. Taken together, our findings suggest that GPC3 regulates HCC cell proliferation with the involvement of Hippo pathway.

The study aimed to investigate the associations between maternal lifestyles and antenatal stress and anxiety. 1491 pregnant women were drawn from the Guangxi birth cohort study (GBCS). A base line questionnaire was used to collect demographic information and maternal lifestyles. The Pregnancy Stress Rating Scale (PSRS) and Self-Rating Anxiety Scale (SAS) were used to assess prenatal stress and anxiety, respectively. Regression analyses identified the relationship between maternal lifestyles and prenatal stress and anxiety: (1) Hours of phone use per day was positively correlated to prenatal stress and anxiety and increased with stress and anxiety levels (all P trend < 0.05). In addition, not having baby at home was positively correlated to prenatal stress. (2) Self-reported sleep quality was negative with prenatal stress and anxiety, and decreased with stress and anxiety levels (all P trend < 0.01). Moreover, not frequent cooking was negatively correlated to prenatal stress and having pets was negatively correlated to prenatal anxiety (P < 0.05). However, having pets was not correlated to prenatal stress (P > 0.05). Our results showed that adverse lifestyles increase the risk of antenatal stress and anxiety, a regular routine and a variety of enjoyable activities decreases the risk of prenatal stress and anxiety.

Abstract. Glypican-3 (GPC3) is a membrane heparan sulfate proteoglycan involved in cell proliferation, differentiation, adhesion, migration and the development of the majority of mesodermal tissues and organs. GPC3 has been found to be important for the occurrence and development of hepatocellular carcinoma (HCC). Therefore, it may be suitable for use as a novel molecular marker for the diagnosis of primary liver cancer. In the present study, the role of GPC3 in the occurrence and development of HCC was determined. GPC3 recombinant vector was transfected into two HCC cell lines, Huh7 and SK-HEP-1, to upregulate the expression of GPC3 and examine changes in the biological behavior of the cells. Results indicate that overexpression of GPC3 in Huh7 and SK-HEP-1 cells effectively inhibited cell proliferation and cell invasion through induction of apoptosis. However, cotreatment of the cells with insulin-like growth factor 2 (IGF2) and fibroblast growth factor 2 (FGF2) was found by Annexin V-PI flow cytometric analysis to significantly inhibit the apoptotic cell death induced by GPC3 overexpression. These observations indicate that GPC3 may act as a negative regulator of IGF2 and FGF2 pathways. Taken together, these results demonstrate that overexpression of GPC3 inhibits the occurrence and development of HCC.

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Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.