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  • ganciclovir FOLE was recently approved for use in PN

    2022-05-13

    FOLE was recently approved for use in PN-dependent patients in the United States. However, potential adverse effects of FOLE, including bleeding risk, and effects on the immune system [8], [39], render its use in certain patient populations controversial. Identification of key downstream modulators of PN-induced liver injury may provide a starting point for the development of alternative, more targeted therapies for PN-induced liver injury that do not rely on changes to the nutritional content of patients’ PN.
    Acknowledgments A license agreement ganciclovir for the use of Omegaven® has been signed by Boston Children's Hospital and Fresenius Kabi. Mark Puder and Kathleen Gura hold an issued patent on the treatment of parenteral nutrition-associated liver disease. They both serve on the Scientific Advisory Board for Pronova-BASF. Kathleen Gura also serves on the Pharmaceutical Advisory Board for B. Braun USA.
    Sources of support in the form of grants This work was funded by the National Institutes of Health grants 1F32DK104525-01 (GLF) and 5T32HL007734 (MAB and DTD), the Boston Children's Hospital Surgical Foundation, and the Howard Hughes Medical Institute (BSC).
    Introduction During early pregnancy, decidualization is essential for successful embryo implantation and the maintenance of pregnancy. Decidualization deficiency or abnormality is one of the major maternal causes of recurrent spontaneous abortions (RSA) [1,2]. Nevertheless, the critical molecular mechanisms governing decidualization and the pathology of decidualization deficiency-related pregnancy complications remain largely unknown. Decidualization is characterized by the transformation of human endometrial stromal ganciclovir (HESCs) to decidua stromal cells (DSCs) that is initiated by dynamic change of progesterone (P4) and estrodiol (E2) level and continues to progress if conception occurs [3]. In response to P4-mediated activation of cyclic adenosine monophosphate (cAMP) signaling, HESCs undergo vast expansion and differentiation. Morphologically, DSCs are charaterized by enlarged cellular size, rounded nucleus with increased number and complexity of the nucleoli, expanded secretory apparatus with dilatation of the rough endoplasmic accumulation of glycogen and lipid droplets, suggesting a need for accelerated biosynthesis and energy supply during decidualization [4]. Actually, it is known that enhanced glucose influx and metabolism are essential for decidualization and pregnancy [5]. DSCs produce insulin-like growth factor-binding protein-1 (IGFBP-1) and prolactin (PRL) which are commonly used as markers of decidualization [6]. DSCs function to regulate the proliferation and invasion of trophoblast and induce decidual differentiation of HESCs by autocrine secretion. Moreover, DSCs interact with decidual immune cells (DICs) to establish the Th2 type maternal-fetal interface, allowing normal decidualization and embryo implantation [7,8]. For example, the recruitment and education of decidual NK (dNK) cells, which account for the largest proportion of DICs, largely depend on chemokines and cytokines secreted by DSCs. Therefore, increased glucose metabolism and the immunoregulatory function of DSCs render sufficient energy, biosynthesis and proper immune microenvironment for decidualization. ω-3 Polyunsaturated fatty acids (PUFAs) including Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) are commonly used nutritional supplements during pregnancy, which can maintain gestation length and fetal growth, prevent preterm birth and decrease the rate of gestational diabetes [[9], [10], [11]]. G-protein-coupled receptor 120 (GPR120), the receptor of ω-3 PUFAs, has been implicated in the pathogenesis of diabetes, cancers and inflammatory diseases [12,13]. GPR120 can regulate various celluar functions, including differentiation, proliferation, glucose metablism and immune response [14]. Although whether GPR120 plays a role in decidualization and pregnancy is still unknown, the expression of GPR120 in human placenta was determined in a recent paper [15]. Taken together, the previous studies indicate that GPR120 may function during decidualization and pregnancy.