Although diagnosis and treatment of gastric cancer have improved, the prognosis of patients remains poor. The majority of patients should be treated with chemotherapy or other follow-up treatment. However, the drug resistance of chemotherapy and heterogeneity of tumor itself lead to differences of sensitivity of chemotherapy drugs for different patients. Therefore, it is mandatory to develop better methods of treatment for treatment of gastric cancer. Calycosin has been used in several types of cancer cells. Cisplatin, 5-fluorouracil (5-FU), and adriamycin (ADM) are most widely used drugs for chemotherapy, and they improve the overall survival of cancer patients. To study whether and how calycosin enhances their inhibition of gastric cancer cells, we detected the signaling pathway in which calycosin and cisplatin, 5-FU, and ADM play role in human gastric cells lines. We found that calycosin can enhance the suppression of cisplatin to gastric cell line by inhibiting the phosphorylation of protein kinase B (Akt). So, when cisplatin/5-FU/ADM is combined with calycosin, it can achieve better therapeutic effect in lower concentration.

Maternal tolerance to semi‐ or fully allograft conceptus is a prerequisite for the maintenance of pregnancy. Once this homeostasis is disrupted, it may result in pregnancy loss. As a potential approach to prevent pregnancy loss, targeting decidual immune cells (DICs) at the maternal‐fetal interface has been suggested. Although the phenotypic features and functions of DIC have been extensively profiled, the regulatory pathways for this unique immunological adaption have yet to be elucidated. In recent years, a pivotal mechanism has been highlighted in the area of immunometabolism, by which the changes in intracellular metabolic pathways in DIC and interaction with the adjacent metabolites in the microenvironment can alter their phenotypes and function. More inspiringly, the manipulation of metabolic profiling in DIC provides a novel avenue for the prevention and treatment of pregnancy loss. Herein, this review highlights the major metabolic programs (specifically, glycolysis, ATP‐adenosine metabolism, lysophosphatidic acid metabolism, and amino acid metabolism) in multiple immune cells (including decidual NK cells, macrophages, and T cells) and their integrations with the metabolic microenvironment in normal pregnancy. Importantly, this perspective may help to provide a potential therapeutic strategy for reducing pregnancy loss via targeting this interplay.

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of decidual stromal cells (DSCs), a series of cytokines and immune cells. Insulin-like growth factor 1 (IGF-1) is a low molecular weight peptide hormone with similar metabolic activity and structural characteristics of proinsulin, which exerts its biological effects by binding with its receptor. Emerging evidence has shown that IGF-1 is expressed at the maternal-fetal interface, but its special role in establishment and maintenance of pregnancy is largely unknown. Here, we found that the expression of IGF-1 in the decidua was significantly higher than that in the endometrium. Additionally, decidua from women with normal pregnancy had high levels of IGF-1 compared with that from women with unexplained recurrent spontaneous miscarriage. Estrogen and progesterone led to the increase of IGF-1 in DSCs through up-regulating the expression of WISP2. Recombinant IGF-1 or DSCs‐derived IGF-1 increased the survival, reduced the apoptosis of DSCs, and downregulated the cytotoxicity of decidual NK cells (dNK) through interaction with IGF-1R. These data suggest that estrogen and progesterone stimulate the growth of DSCs and impair the cytotoxicity of dNK possibly by the WISP2/IGF-1 signaling pathway.

In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions, has also been implicated in many diseases. Recently, it is also surmised to be correlated with SM. However, the detailed mechanism remains elusive. In fact, there are several essential steps during pregnancy establishment and maintenance: trophoblasts invasion, placentation, decidualization, enrichment and infiltration of decidua immune cells (e.g., natural killer, macrophage and T cells). Accordingly, upstream molecules and downstream effects of autophagy are discussed in these processes, respectively. Of note, autophagy regulates the crosstalk between these cells at the maternal-fetal interface as well. Aberrant autophagy is found in villi, decidual stromal cells, peripheral blood mononuclear cells in SM patients, although the findings are inconsistent among different studies. Furthermore, potential treatments targeting autophagy are included, during which rapamycin and vitamin D are hot-spots in recent literatures. To conclude, a moderately activated autophagy is deeply involved in pregnancy, suggesting that autophagy should be a regulator and promising target for treating SM.

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