Upregulation of ENDOU in cytotrophoblasts from placenta complicated with preeclampsia and fetal growth restriction.

Placental hypoplasia is associated with the pathophysiology of fetal growth restriction and preeclampsia. The placenta consists of differentiated trophoblasts, including cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts. Cytotrophoblasts are thought to have stem-like characteristics and the ability to differentiate into syncytiotrophoblasts and extravillous trophoblasts. However, it is poorly understood whether isolated cytotrophoblasts derived from hypoplastic placentas have specific features compared with those in normal placentas. This study aimed to determine the features of cytotrophoblasts in hypoplastic placentas. Differentially expressed proteins between isolated cytotrophoblasts from hypoplastic placenta with fetal growth restriction and those from the normal placenta were determined by liquid chromatography-tandem mass spectrometry. Among 6,802 proteins, 1,253 and 2,129 proteins were more than 2-fold upregulated and downregulated, respectively. Among them, ENDOU (endonuclease, poly(U) specific), which has high homology with the coronavirus endoribonuclease nonstructural protein 15 (Nsp15), showed a significantly increased expression in cytotrophoblasts from the placenta with fetal growth restriction related to preeclampsia compared with those in normal control placenta. These results provide insight into the pathological mechanisms of placental hypoplasia and additional information on preeclamptic symptoms in cases of SARS-CoV-2 infected placenta, although further investigation is needed.

IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction.

Hepatitis C virus inhibitor synergism suggests multistep interactions between heat-shock protein 90 and hepatitis C virus replication.

AIM: To address the effect of heat-shock protein 90 (HSP90) inhibitors on the release of the hepatitis C virus (HCV), a cell culture-derived HCV (JFH1/HCVcc) from Huh-7 cells was examined. METHODS: We quantified both the intracellular and extracellular (culture medium) levels of the components (RNA and core) of JFH-1/HCVcc. The intracellular HCV RNA and core levels were determined after the JFH1/HCVcc-infected Huh-7 cells were treated with radicicol for 36 h. The extracellular HCV RNA and core protein levels were determined from the medium of the last 24 h of radicicol treatment. To determine the possible role of the HSP90 inhibitor in HCV release, we examined the effect of a combined application of low doses of the HSP90 inhibitor radicicol and the RNA replication inhibitors cyclosporin A (CsA) or interferon. Finally, we statistically examined the combined effect of radicicol and CsA using the combination index (CI) and graphical representation proposed by Chou and Talalay. RESULTS: We found that the HSP90 inhibitors had greater inhibitory effects on the HCV RNA and core protein levels measured in the medium than inside the cells. This inhibitory effect was observed in the presence of a low level of a known RNA replication inhibitor (CsA or interferon-α). Treating the cells with a combination of radicicol and cyclosporin A for 24 h resulted in significant synergy (CI < 1) that affected the release of both the viral RNA and the core protein. CONCLUSION: In addition to having an inhibitory effect on RNA replication, HSP90 inhibitors may interfere with an HCV replication step that occurs after the synthesis of viral RNA, such as assembly and release.