Decidualization-associated recruitment of cytotoxic memory CD8T cells to the maternal-fetal interface for immune defense.

Decidual CD8T (dCD8T) cells are pivotal in the maintenance of the delicate balance between immune tolerance towards the fetus and immune resistance against pathogens. The endometrium and decidua represent the uterine environments before and during pregnancy, respectively, yet the composition and phenotypic alterations of uterine CD8T cells in these tissues remain unclear. Using flow cytometry and analysis of transcriptome profiles, we demonstrated that human dCD8T and endometrial CD8T (eCD8T) cells exhibited similar T cell differentiation statuses and phenotypes of tissue infiltrating or residency, compared to peripheral CD8T (pCD8T) cells.

CX3CL1 (Fractalkine): An important cytokine in physiological and pathological pregnancies.

C-X3-C motif chemokine ligand 1 (CX3CL1), commonly known as Fractalkine, is an important chemokine with dual functions of chemotaxis and adhesion. It plays a pivotal role in a variety of physiological processes and pathological conditions, particularly in conjunction with its receptor, C-X3-C motif chemokine receptor 1 (CX3CR1). This review focuses on the expression and intricate regulatory mechanisms of CX3CL1 at the maternal-fetal interface, emphasizing its multifaceted role during pregnancy.

CD36-mediated arachidonic acid influx from decidual stromal cells increases inflammatory macrophages in miscarriage.

Spontaneous abortion is associated with aberrant lipid metabolism, but the underlying mechanisms remain unclear. Here, we show that lipids are accumulated in decidual stromal cells (DSCs) and macrophages (dMφs) in women with miscarriage and mouse abortion-prone models. Moreover, we show that excessive lipids from DSCs are transferred to dMφs via a CD36-dependent mechanism that induces inflammation in dMφs.

A Galectin-9-Driven CD11c Decidual Macrophage Subset Suppresses Uterine Vascular Remodeling in Preeclampsia.

Background: Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear.

Methods: Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia.

Macrophage plasticity and function in cancer and pregnancy.

As the soil of life, the composition and shaping process of the immune microenvironment of the uterus is worth exploring. Macrophages, indispensable constituents of the innate immune system, are essential mediators of inflammation and tissue remodeling as well. Recent insights into the heterogeneity of macrophage subpopulations have renewed interest in their functional diversity in both physiological and pathological settings.

Downregulation of CRHBP is associated with trophoblast invasion inhibition in recurrent pregnancy loss.

In Brief: Corticotropin-releasing hormone binding protein (CRHBP) is fundamental to the stress response and plays an important role in parturition during pregnancy. This study shows that abnormal CRHBP expression could be an early warning sign of recurrent pregnancy loss and that CRHBP knockdown could suppress HTR8/SVneo cell invasion by the PKC signaling pathway via interacting with CRH receptor 2.

Abstract: Trophoblast invasion is critical for placentation and pregnancy success.

Surface-decorated nanoliposomal leonurine targets activated fibroblast-like synoviocytes for efficient rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes progressive joint destruction, leading to impaired life quality, disability, and even premature mortality. However, current medications suffer from limited clinical outcomes and severe side effects due to low bioavailability and non-specific distribution after administration. Herein, a targeting nanosystem (HAP-Lipo@Leo) was constructed for efficient RA treatment, which can precisely deliver a natural anti-arthritic drug leonurine (Leo) to the inflamed joint by HAP-1 peptide-mediated recognition of activated fibroblast-like synoviocytes (FLS).

The unique expression pattern of human leukocyte antigen in trophoblasts potentially explains the key mechanism of maternal-fetal tolerance and successful pregnancy.

The success of pregnancy mainly depends on immune tolerance of the mother for the semi-allogeneic fetus. The placenta carrying paternal antigens develops in the maternal uterus without suffering immune attack, making the underlying mechanism of maternal tolerance an enduring mystery. As we all know, human leukocyte antigen (HLA) plays an important role in antigen processing and presentation, thus inducing specific immune responses.

Paradoxical expression of NRP1 in decidual stromal and immune cells reveals a novel inflammation balancing mechanism during early pregnancy.

Objective And Design: To investigate the balancing mechanisms between decidualization-associated inflammation and pregnancy-related immunotolerance.

Material Or Subjects: Decidual samples from women with normal pregnancy (n = 58) or unexplained spontaneous miscarriage (n = 13), peripheral blood from normal pregnancy and endometria from non-pregnancy (n = 10) were collected. Primary endometrial stromal cells (ESCs), decidual stromal cells (DSCs), decidual immune cells (DICs) and peripheral blood mononuclear cells (PBMCs) were isolated.

Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity.

Ischemic stroke (IS) constitutes the leading cause of global morbidity and mortality. Neuroprotectants are essential to ameliorate the clinical prognosis, but their therapeutic outcomes are tremendously compromised by insufficient delivery to the ischemic lesion and intricate pathogenesis associated with neuronal damage, oxidative stress, inflammation responses, blood-brain barrier (BBB) dysfunction, . Herein, a biomimetic nanosystem (Leo@NM-Lipo) composed of neutrophil membrane-fused nanoliposomal leonurine (Leo) is constructed, which can not only efficiently penetrate and repair the disrupted BBB but also robustly remodel the harsh cerebral microenvironment to reverse ischemia-reperfusion (I/R) injury.

Injectable leonurine nanocrystal-loaded microspheres for long-term hyperlipidemia management.

Hyperlipidemia is a lipid metabolism disorder that requires long-term and daily medication. Leonurine (Leo), an active alkaloid derived from , can effectively ameliorate lipid profiles in mammals and serve as a candidate antihyperlipidemic agent for clinical applications. In this paper, poly(lactic--glycolic acid) (PLGA) microsphere (MP)-based drug delivery platforms were for the first time employed for hyperlipidemia management by encapsulating leonurine nanocrystals (Leo-nano) by a modified solid-in-oil-in-water (S/O/W) double emulsion-solvent emulsion technique.

Decidual Stromal Cell Ferroptosis Associated with Abnormal Iron Metabolism Is Implicated in the Pathogenesis of Recurrent Pregnancy Loss.

Iron is necessary for various critical biological processes, but iron overload is also dangerous since labile iron is redox-active and toxic. We found that low serum iron and decidual local iron deposition existed simultaneously in recurrent pregnancy loss (RPL) patients. Mice fed with a low-iron diet (LID) also showed iron deposition in the decidua and adverse pregnancy outcomes.

cAMP/PKA signaling promotes AKT deactivation by reducing CIP2A expression, thereby facilitating decidualization.

cAMP signaling is widely known to be indispensable for decidualization, but the details are not fully understood. Here, we show that cAMP signaling promotes AKT deactivation in endometrial stromal cells, which favors their decidualization. The deactivation of AKT is found to be a consequence of the reduced expression of several inhibitors of PP2A, the major phosphatase of AKT, with CIP2A being the most prominent.

Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance.

T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal-fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal-fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking defects in pregnant mice treated with Tim-3 neutralizing antibodies.

Dysfunction of CCR1 decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) puzzles 1-3% of women of childbearing age worldwide. Immunological factors account for more than 60% of cases of unexplained RPL (URPL); however, the underlying mechanism remains unclear. Here, using single-cell sequencing data and functional experiments with clinical samples, we identified a distinct population of CCR1 decidual macrophages (dMφ) that were preferentially enriched in the decidua from normal early pregnancies but were substantially decreased in patients with URPL.

Circadian gene Rev-erbα influenced by sleep conduces to pregnancy by promoting endometrial decidualization via IL-6-PR-C/EBPβ axis.

Background: Sleep disturbance can cause adverse pregnancy outcomes by changing circadian gene expression. The potential mechanisms remain unclear. Decidualization is critical for the establishment and maintenance of normal pregnancy, which can be regulated by circadian genes.

Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia.

Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs.

The Critical Roles of Circular RNAs in Basic Research and Clinical Application of Female Reproductive-Related Diseases.

Circular RNAs (circRNAs), produced by precursor mRNAs, are a type of covalently closed circular molecule without 5' caps and 3' polyadenylated tails. Recently, advances in high-throughput sequencing, transcriptomics and bioinformatics, have revealed that circRNAs with specific traits in tissue or cells play emerging roles in both physiological and panthological contexts instead of as simple by-products of transcription. However, bringing circRNAs to the forefront of clinical practice is still a long way off.

RhoB Promotes Endometrial Stromal Cells Decidualization Via Semaphorin3A/PlexinA4 Signaling in Early Pregnancy.

Endometrial decidualization refers to a series of morphological changes and functional remodeling of the uterine endometrium to accept the embryo under the effect of estrogen and progesterone secreted by ovaries after ovulation. During decidualization, endometrial stromal cells (ESCs) proliferate and differentiate into decidual stromal cells, undergoing cytoskeletal rearrangement-mediated morphological changes and expressing decidualization markers, such as insulin-like growth factor-binding protein-1 and prolactin. Ras homology (Rho) proteins, a family of small G proteins, are well known as regulators of cellular morphology and involved in multiple other cellular processes.

SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell Balancing ERα and PR Signals.

Background: Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation.