Circ-CCNB1 Modulates Trophoblast Proliferation and Invasion in Spontaneous Abortion by Regulating miR-223/SIAH1 axis.

CONTEXT: Spontaneous abortion (SA) is a common disorder in early pregnancy. Circular RNAs (circRNAs) have been reported to exert important regulatory effects on trophoblast function and embryo development. OBJECTIVE: The aim of this study was to explore whether and how circRNAs regulate trophoblast function in SA during early pregnancy. METHODS: Cell proliferation, 5-bromo-2-deoxyuridine (BrdU) staining, Transwell, immunofluorescence, Western blot, RNA pull-down, and dual luciferase reporter assays were performed to investigate the effect of circRNA cyclin B1 (circ-CCNB1) on trophoblast function in HTR-8/SVneo and JEG-3 cells. RESULTS: An in vitro study demonstrated that upregulation of circ-CCNB1 significantly inhibited trophoblast proliferation and invasion compared with the controls using HTR-8/SVneo and JEG-3 cells, respectively. Moreover, miR-223 was downregulated in the villous tissues of patients with SA and was further predicted and shown to negatively interact with circ-CCNB1, which is involved in trophoblast proliferation and invasion. Using bioinformatics tools and subsequent RNA pull-down and dual luciferase assays, we found that miR-223 directly targets seven in absentia homolog-1 (SIAH1) and that upregulation of miR-223 decreased circ-CCNB1-induced SIAH1 expression levels in HTR-8/SVneo cells. Interestingly, upregulation of circ-CCNB1 suppressed trophoblast proliferation and invasion through inhibition of CCNB1 nuclear translocation induced by SIAH1. Downregulation of SIAH1 enhanced circ-CCNB1-suppressed CCNB1 nuclear protein expression in trophoblast cells. CONCLUSION: Circ-CCNB1 served as a modulator of trophoblast proliferation and invasion by sponging miR-223, thus forming a regulatory network of circ-CCNB1/miR-223/SIAH1 in modulating CCNB1 nuclear translocation, which enabled us to elucidate the molecular mechanisms involved in normal embryo implantation or in SA.

Insights into the immunomodulatory regulation of matrix metalloproteinase at the maternal-fetal interface during early pregnancy and pregnancy-related diseases.

Trophoblast immune cell interactions are central events in the immune microenvironment at the maternal-fetal interface. Their abnormalities are potential causes of various pregnancy complications, including pre-eclampsia and recurrent spontaneous abortion. Matrix metalloproteinase (MMP) is highly homologous, zinc(II)-containing metalloproteinase involved in altered uterine hemodynamics, closely associated with uterine vascular remodeling. However, the interactions between MMP and the immune microenvironment remain unclear. Here we discuss the key roles and potential interplay of MMP with the immune microenvironment in the embryo implantation process and pregnancy-related diseases, which may contribute to understanding the establishment and maintenance of normal pregnancy and providing new therapeutic strategies. Recent studies have shown that several tissue inhibitors of metalloproteinases (TIMPs) effectively prevent invasive vascular disease by modulating the activity of MMP. We summarize the main findings of these studies and suggest the possibility of TIMPs as emerging biomarkers and potential therapeutic targets for a range of complications induced by abnormalities in the immune microenvironment at the maternal-fetal interface. MMP and TIMPs are promising targets for developing new immunotherapies to treat pregnancy-related diseases caused by immune imbalance.

Loss of miR-29a impairs decidualization of endometrial stromal cells by TET3 mediated demethylation of Col1A1 promoter.

A conceptual framework for understanding abnormal endometrial decidualization, with considerable significance for the diagnosis and treatment of abnormal decidualization-related changes in non-receptive endometrium in implantation failure during early pregnancy is very important. Here, we found the expression levels of miR-29a in endometrial tissues were associated with the menstrual phases and pregnancy outcome. Inhibition of miR-29a led to decreased decidualization of endometrial stromal cells (ESCs) in vitro, whereas Tet methylcytosine dioxygenase 3 (TET3) and its potential demethylation target, the collagen type I alpha 1 chain (Col1A1), were restored. The binding capacity of TET3 to the Col1A1 promoter could be enhanced by the inhibition of miR-29a. Finally, deletion of TET3 rescued the inhibitory effect of the miR-29a antagomir on the proliferation of decidualized ESCs in vitro and embryo implantation in vivo. Thus, loss of miR-29a causes implantation failure because of the limitation of ESCs decidualization-related changes in non-receptive endometrium during early pregnancy.

Silver nanoparticle-decorated TiO2 nanotube array for solid-phase microextraction and SERS detection of antibiotic residue in milk.

The excessive use or abuse of antibiotics on dairy cows leads to residues in milk, which can represent a public health risk. However, in recent years the ß-Lactamase was illegally used to degrade residual antibiotics in milk, which makes the traditional antibiotic detection methods ineffective. Therefore, there is an extremely urgent need for multi-analyte analysis techniques for the detection of antibiotic residues. Herein, we reported an ultra-fast, facile, and sensitive solid-phase microextraction (SPME)-surface enhanced Raman scattering (SERS) platform for the detection of degraded antibiotics-2-mercapto-5-methyl-1,3,4-thiadiazole (MMT). The results showed that the log-log plot of SERS intensity to MMT concentration exhibits a superior linear relationship (R2 = 0.992) in the concentration range of 0.5-1000 µM, with a detection limit of 0.11 µM. The silver nanoparticle-decorated TiO2 nanotube array was successfully used as an all-in-one SPME-SERS substrate in the extraction and identification of the antibiotic degradation products in real milk. Due to the rapid pre-treatment, good reproducibility, and self-cleaning, the proposed SPME-SERS method has a great promise to be applied as a powerful tool for on-site detection in the field of food safety.