Xiao-Ming Zhu

Introduction: Preeclampsia is a pregnancy-specific hypertensive disorder associated with abnormal trophoblast function. MicroRNA-181a (miR-181a) has been implicated in placental development, but its role in trophoblast behavior and its interaction with estrogen receptor 1 (ER1) remain unclear. This study aimed to investigate the functional role of miR-181a in trophoblast proliferation and migration and to determine whether ER1 mediates these effects in the context of preeclampsia. Methods: Methods: Placental tissues were collected from 30 PE patients and 26 healthy controls. Expression levels of miR-181a and ESR1 were quantified by qRT-PCR. The effects of miR-181a on trophoblast viability, proliferation, and migration were assessed using CCK-8 and Transwell assays. The direct targeting of ESR1 by miR-181a was validated via dual-luciferase reporter assays. Results: Results: miR-181a was significantly upregulated in PE placental tissues compared to controls (P < 0.001), whereas ESR1 expression was markedly downregulated (P < 0.001). A significant negative correlation between miR-181a and ESR1 levels was observed (P < 0.001). Functional assays revealed that miR-181a overexpression (OE) promoted trophoblast proliferation and migration, whereas its inhibition exerted opposite effects. Luciferase reporter assays confirmed direct binding of miR-181a to the 3'-UTR of ESR1, leading to reduced ESR1 expression. Ectopic ESR1-OE reversed the effects of miR-181a on trophoblast viability and migration. Discussion: Our findings demonstrate that miR-181a negatively regulates trophoblast proliferation and migration, and that ER1 is a direct target of miR-181a. Downregulation of miR-181a restored trophoblast function, suggesting a potential therapeutic target for preeclampsia. These results align with prior studies linking miRNA dysregulation to placental insufficiency. However, this study is limited by its in vitro design, and future in vivo validation is warranted to confirm the clinical relevance of miR-181a-ER1 signaling in preeclampsia pathogenesis. Conclusion: miR-181a contributes to PE pathogenesis by negatively regulating ESR1, thereby impairing trophoblast proliferation and migration. These findings provide novel insights into the molecular mechanisms of PE and suggest miR-181a as a potential diagnostic or therapeutic target.

Background: The adenosine–adenosine receptor pathway plays important roles in the immune system and inflammation. Four adenosine receptors (i.e., A1R, A2AR, A2BR, and A3R) have been identified. However, the roles of these receptors were different in the disease progress and even play opposite roles in the same disease. This study aims to investigate the roles of A1R/A2AR/A2BR/A3R activation in liver fibrosis.Methods: Intraperitoneal injection of CCl₄ into C57BL/6 mice was used to induce liver fibrosis in the models. Adenosine receptor agonists CCPA, CGS21680, BAY 60-6583, and namodenoson were used for A1R/A2AR/A2BR/A3R activation, respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were used to evaluate the liver function. Hematoxylin and eosin (H&E) staining was used to investigate the pathological damage. Masson staining and Sirius Red staining were performed to evaluate the degree of collagen deposition. CCK8 and scratch assays were used to investigate the proliferation and migration ability of hepatic stellate cells (HSCs).Results: By using liver fibrosis mouse models, we observed that the A1R and A2AR agonists aggravated liver fibrosis, characterized by increasing ALT and AST levels, more serious liver pathological damage, and collagen deposition. However, the A2BR and A3R agonists alleviated liver fibrosis. Moreover, the A1R and A2AR agonist treatment promotes the proliferation and migration of HSC line LX2, while A2BR and A3R agonist treatment inhibited LX2 proliferation and migration. Consistently, A1R and A2AR agonist treatment elevated the expression of α-SMA and Col1α1 in LX2, whereas A2BR and A3R agonist treatment inhibited the expression of α-SMA and Col1α1 in LX2 cells. Additionally, 5′-N-ethyl-carboxamidoadenosine (NECA), a metabolically stable adenosine analog, alleviated liver fibrosis and inhibited LX2 cell activity, proliferation, and migration.Conclusion: This study demonstrated the different roles of A1R/A2AR/A2BR/A3R during liver fibrosis development via regulating the HSC activity and proliferation.

Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal–fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal–fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal–fetal tolerance based on maternal–fetal crosstalk. Insights into maternal–fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Objective: To explore the DPP4 expression changes and functions in ovarian cancer (OV), as well as the regulation mechanism for DDP4. Methods: GEPIA2, GSE18520, GSE26712 and UALCAN were used to analyze differences in DPP4 expression between OV tumors and control tissues. Serum DPP4 levels were measured by ELISA. The prognostic values of DPP4 were evaluated using a Kaplan–Meier (KM) plotter. Small interfering RNA was used for DPP4 knockdown in OVCAR-3 and SKOV-3 cells. CCK-8 and scratch healing assays were used to determine the cells’ proliferation and migration abilities. Flow cytometry (FCM) was used to detect the cell cycle and apoptosis. A dual-luciferase assay was designed to confirm the regulatory effect of miR-29a-3p on DPP4. Results: The expressions of DPP4 mRNA and protein were decreased in OV tumor tissues. Serum DPP4 levels decreased in OV patients. KM plotter analysis showed correlation between high DPP4 expression and a poor prognosis in OV patients. By targeting knockdown of DPP4, we found that OVCAR-3 and SKOV-3 cells’ proliferation was inhibited, while cell’s migration ability was significantly promoted. FCM analysis showed that DPP4 knockdown induced a decrease in the S phase. Furthermore, DPP4 was shown to be downregulated by miR-29a-3p and TGFβ1 in OVCAR-3 cells, and miR-29a-3p expression was upregulated by TGFβ1. The effects of miR-29a-3p and TGFβ1 on OVCAR-3 cells’ biological behaviors were consistent with DPP4 knockdown. Conclusion: DPP4 was downregulated in OV patients. DPP4 knockdown significantly inhibited OVCAR-3 and SKOV-3 cell proliferation and promoted cell migration. DDP4 can be downregulated by TGFβ1 through the upregulation of miR-29a-3p in OV cells.

This study was conducted to illustrate the origin of these PE-related ncRNAs in maternal circulation and their underlying transport methods into target cells. We selected 10 women with severe pre-eclampsia (PE group) and 10 healthy participants who served as controls (NC group). Exosomes were isolated from their sera and their origin was determined by a specific marker, placental alkaline phosphatase (PLAP). We compared the ncrna associated with PE in exosomes and whole serum to observe the exchange of serum exosomes with trophoblast cells. The results showed that PLAP was enriched in the isolated exosomes. Seven PE-associated ncRNAs, including lnc-SNHG5, miR-26a-5p, miR-221-3p, miR-30a-3p, miR-18a, miR-152 and miR-155, were analyzed in placenta-derived exosomes and whole serum from both groups. miR-26a-5p, miR-152 and miR-155 were upregulated in the PE group compared with the NC group. 152 and miR-155 were upregulated. 152 and miR-155 were upregulated, while miR-18a and miR-221-3p were downregulated (P<0.05). ncRNAs were altered in serum and placenta-derived serum exosomes in a consistent trend. Fluorescence microscopy results showed that the nuclei were counterstained in HTR-8 cells exposed to PKH26-labeled exosomes. PE-associated ncRNAs can enter the maternal circulation through secretion and encapsulation into placenta-derived exosomes and participate in the development and progression of PE by targeting trophoblast cells. differential expression of ncRNAs in exosomes has the potential to be used as predictors for targeted therapy, providing new ideas and perspectives for improving maternal and infant outcomes.

The chemokine CXCL12 and its receptor CXCR4 are important signaling components required for human blastocyst implantation and the progression of pregnancy. Growing evidence indicates that the CXCL12/CXCR4 axis can regulate trophoblast function and uterine spiral artery remodeling, which plays a fundamental role in placentation and fetal outcome. The orphan receptor CXCR7 is also believed to partly regulate the function of the CXCL12/CXCR4 axis. Additionally, the CXCL12/CXCR4/CXCR7 axis can enhance the cross-talk between trophoblasts and decidual cells such as uterine natural killer cells and decidual stromal cells which are involved in regulation of trophoblast differentiation and invasion and placental angiogenesis. In addition, recent studies proved that CXCL12 expression is elevated in the placenta and mid-trimester amniotic fluid of pregnant women with preeclampsia, implying that dysregulation of CXCL12 plays a role in the pathogenesis of preeclampsia. Further understanding of the regulatory mechanisms of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis may help to design novel therapeutic approaches for pregnancy-associated diseases. FullText for HTML: https://doi.org/10.1093/abbs/gmv064