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Changwon Yang, Gwonhwa Song and Whasun Lim

In humans, pregnancy maintenance depends on normal placental formation following trophoblast invasion into the endometrium and vascular remodeling. In the early stages of pregnancy, immune tolerance, inflammatory response and adaptation to hypoxia need to be precisely regulated in the placental microenvironment. Various types of cells, such as trophoblasts, endothelial cells, immune cells, mesenchymal stem cells (MSCs) and adipocytes, induce normal placental development via intercellular interactions through soluble factors. Extracellular vesicles (EVs) are used to diagnose various diseases because their constituents vary depending on the type of cell of origin and pathological characteristics. EV-derived microRNAs (miRNAs) and proteins in the placenta regulate inflammatory responses and the invasion of trophoblasts through intercellular delivery in the placental microenvironment. If the placenta does not adapt to the changed environment during early pregnancy, pregnancy disorders such as pre-eclampsia, preterm birth and gestational diabetes mellitus can occur. Thus, the important roles of EVs during pregnancy and development is fast emerging. This review describes the physiological role of EVs during placentation and their composition in the human placenta. It also suggests the possibility of finding EV markers that can diagnose pregnancy disorders. Furthermore, it describes the properties of EVs that affect pregnancy in livestock.

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Jin-Young Lee, Jiyeon Ham, Whasun Lim and Gwonhwa Song

Apomorphine is a derivative of morphine that is used for the treatment of Parkinson’s disease because of its effects on the hypothalamus. Therapeutic effects of apomorphine have also been reported for various neurological diseases and cancers. However, the molecular mechanisms of the antitumor effects of apomorphine are not clear, especially with respect to choriocarcinoma. This is the first study to elucidate the anticancer effects of apomorphine on choriocarcinoma. We found that apomorphine suppressed the viability, proliferation, ATP production, and spheroid formation of JEG3 and JAR choriocarcinoma cells. Moreover, apomorphine activated the intrinsic apoptosis pathway by activating caspases and inhibited the production of anti-apoptotic proteins in choriocarcinoma cells. Further, apomorphine caused depolarization of mitochondria, calcium overload, energy deprivation, and endoplasmic reticulum stress in JEG3 and JAR cells. We confirmed synergistic effects of apomorphine with paclitaxel, a traditional chemotherapeutic agent, and propose that apomorphine could be a potential therapeutic agent in choriocarcinoma and an important candidate for drug repositioning that could help overcome resistance to conventional chemotherapy.

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Jin-Young Lee, Hahyun Park, Whasun Lim and Gwonhwa Song

α,β-Thujone is a natural terpenoid found in many medicinal herbs, such as Artemisia absinthium (wormwood), that exhibits antioxidant, anti-diabetic, and anti-tumorigenic effects. α,β-Thujone has numerous functions; it serves as a food ingredient, cosmetic additive, and medicinal remedy. Although the therapeutic properties of α,β-thujone were previously revealed, a comprehensive description of the mechanisms of its anti-cancer potential in choriocarcinoma is yet to be provided. To our knowledge, this study is the first to demonstrate that α,β-thujone attenuates JEG3 and JAR choriocarcinoma cells through a caspase-dependent intrinsic apoptotic pathway. Moreover, α,β-thujone was demonstrated to induce a global mitochondrial defect and ER stress in choriocarcinoma by causing mitochondrial depolarization, calcium overload, and metabolic alterations, thereby leading to energy deprivation, which eventually contributes to the increase in apoptosis of choriocarcinoma cells. Herein, we also revealed the synergistic anti-cancer activity of α,β-thujone via its sensitization effect on paclitaxel in choriocarcinoma cells. Altogether, our findings suggest that α,β-thujone is a novel, natural pharmacological compound that can be used to treat human placental choriocarcinoma.