The regulated cell death at the maternal-fetal interface: beneficial or detrimental?

Regulated cell death (RCD) plays a fundamental role in placental development and tissue homeostasis. Placental development relies upon effective implantation and invasion of the maternal decidua by the trophoblast and an immune tolerant environment maintained by various cells at the maternal-fetal interface. Although cell death in the placenta can affect fetal development and even cause pregnancy-related diseases, accumulating evidence has revealed that several regulated cell death were found at the maternal-fetal interface under physiological or pathological conditions, the exact types of cell death and the precise molecular mechanisms remain elusive.

Case Report: A novel variant of in fetal genetic osteogenesis imperfecta.

Objective: Osteogenesis imperfecta (OI) is a rare genetic disorder. Clinical severity is heterogeneous. The purpose of this study was to investigate the genetic characteristics of a fetus with OI by whole exome sequencing (WES) and identify the cause of the disease.

Siglecs family used by pathogens for immune escape may engaged in immune tolerance in pregnancy.

The Siglecs family is a group of type I sialic acid-binding immunoglobulin-like receptors that regulate cellular signaling by recognizing sialic acid epitopes. Siglecs are predominantly expressed on the surface of leukocytes, where they play a crucial role in regulating immune activity. Pathogens can exploit inhibitory Siglecs by utilizing their sialic acid components to promote invasion or suppress immune functions, facilitating immune evasion.

Myeloid-derived suppressor cells cross-talk with B10 cells by BAFF/BAFF-R pathway to promote immunosuppression in cervical cancer.

Immunosuppression induced by myeloid-derived suppressor cells (MDSCs) is one of the main obstacles to the efficacy of immunotherapy for cervical cancer. Recent studies on the immunosuppressive ability of MDSCs have primarily focused on T cells, but the effect of MDSCs on B cells function is still unclear. In a study of clinical specimens, we found that the accumulation of MDSCs in patients with cervical cancer was accompanied by high expression of B cell activating factor (BAFF) on the surface and high expression of interleukin (IL)-10-producing B cells (B10) in vivo.

Hypoxia induced ALKBH5 prevents spontaneous abortion by mediating mA-demethylation of SMAD1/5 mRNAs.

The molecules induced by hypoxia have been supposed to be important regulators of first trimester trophoblast activity, but the key mechanism mediating invasion of trophoblast cells is not fully illustrated. Here, we found that the expression of RNA demethylase ALKBH5 was upregulated in trophoblast upon hypoxia treatment and decreased in extravillous trophoblast (EVT) of patients with recurrent spontaneous abortion (RSA). Furthermore, we found that trophoblast-specific knockdown of ALKBH5 in mouse placenta suppressed the invasion of trophoblast and significantly led to fetus abortion in vivo.

A Pyroptosis-Related Gene Panel for Predicting the Prognosis and Immune Microenvironment of Cervical Cancer.

Cervical cancer (CC) is one of the most common malignant tumors of the female reproductive system. And the immune system disorder in patients results in an increasing incidence rate and mortality rate. Pyroptosis is an immune system-related programmed cell death pathway that produces systemic inflammation by releasing pro-inflammatory intracellular components.

Physiological function of the dynamic oxygen signaling pathway at the maternal-fetal interface.

Oxygen is vital for the normal function of cells and is transported to all parts of the body through red blood cells in the vasculature. Abnormal oxygen concentrations can lead to many complications, and reestablishing oxygen balance is essential for cell biological functions. Mammalian cells have evolved to adapt to hypoxia and sense oxygen levels during hypoxia to maintain and coordinate different biological responses.

YTHDF2 inhibit the tumorigenicity of endometrial cancer via downregulating the expression of IRS1 methylated with mA.

RNA epigenetic modification take part in many biology processes, and the N6-methyladenosine (mA) methylation of specific mRNAs in endometrial cancer (EC) tissues play a key role in regulating the tumorigenicity of EC, but the specific mechanism still unknown and need to be investigated in the future. Here, we found that mA reader protein YTHDF2 expression was significantly upregulated in EC compare to tumor adjacent tissues, YTHDF2 was then identified to inhibit the proliferation and invasion of EC cell lines. Mechanistically, the mA reader YTHDF2 bind the methylation sites of target transcripts IRS1 and promoted IRS1 mRNA degradation, consequently inhibiting the expression of IRS1 and inhibiting IRS1/AKT signaling pathway, finally inhibit the tumorigenicity of EC.

The Role of B7 Family Molecules in Maternal-Fetal Immunity.

Pregnancy is a complex but well-arranged process, and a healthy fetus requires immune privilege and surveillance in the presence of paternally derived antigens. Maternal and fetal cells interact at the maternal-fetal interface. The upregulation and downregulation of maternal immunity executed by the leukocyte population predominantly depend on the activity of decidual natural killer cells and trophoblasts and are further modulated by a series of duplex signals.

Cytoplasmic mA reader YTHDF3 inhibits trophoblast invasion by downregulation of mA-methylated IGF1R.

N-methyladenosine (mA) is one of the important post-transcriptional modifications in RNA and plays an important role in promoting translation or decay of mA-methylated messenger RNA (mRNA), but the "reader" protein and the exact biological role of mA remain to be determined. Here, we identified that nine potential mA "reader" proteins including YTH domain family and heterogeneous nuclear ribonucleoprotein by mass spectrometry, and among them, YTH domain-containing protein 3 (YTHDF3), could bind directly to mA-carrying RNA. YTHDF3 was then identified to negatively regulate invasion and migration of trophoblast.

Dynamic Function and Composition Changes of Immune Cells During Normal and Pathological Pregnancy at the Maternal-Fetal Interface.

A successful pregnancy requires a fine-tuned and highly regulated balance between immune activation and embryonic antigen tolerance. Since the fetus is semi-allogeneic, the maternal immune system should exert tolerant to the fetus while maintaining the defense against infection. The maternal-fetal interface consists of different immune cells, such as decidual natural killer (dNK) cells, macrophages, T cells, dendritic cells, B cells, and NKT cells.

[Progress in epigenetic modification of mRNA and the function of m6A modification].

Messenger RNA (mRNA) can be modified by more than 100 chemical modifications. Among these modifications, N6-methyladenosine (m⁶A) is one of the most prevalent modifications. During the processes of cells differentiation, embryo development or stress, m⁶A can be modified on key mRNAs and regulate the progress of cells through modulating mRNA metabolism and translation.

Downregulation of lysyl oxidase and lysyl oxidase-like protein 2 suppressed the migration and invasion of trophoblasts by activating the TGF-β/collagen pathway in preeclampsia.

Preeclampsia is a pregnancy-specific disorder that is a major cause of maternal and fetal morbidity and mortality with a prevalence of 6-8% of pregnancies. Although impaired trophoblast invasion in early pregnancy is known to be closely associated with preeclampsia, the underlying mechanisms remain elusive. Here we revealed that lysyl oxidase (LOX) and LOX-like protein 2 (LOXL2) play a critical role in preeclampsia.

Corrigendum: The RNA helicase DDX46 inhibits innate immunity by entrapping mA-demethylated antiviral transcripts in the nucleus.

This corrects the article DOI: 10.1038/ni.3830.

The RNA helicase DDX46 inhibits innate immunity by entrapping mA-demethylated antiviral transcripts in the nucleus.

DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection.

Type I IFN-Inducible Downregulation of MicroRNA-27a Feedback Inhibits Antiviral Innate Response by Upregulating Siglec1/TRIM27.

Upon recognition of viral components by pattern recognition receptors, including TLRs and retinoic acid-inducible gene I-like helicases, cells are activated to produce type I IFN, which plays key roles in host antiviral innate immune response. However, excessive IFN production may induce immune disorders, and the mechanisms responsible for the regulation of type I IFN production have attracted much attention. Furthermore, type I IFN activates the downstream IFN/JAK/STAT pathway to modulate expression of a set of genes against viral infection, but whether these genes can feedback regulate type I IFN production is poorly understood.

Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27.

Type I interferon (IFN) production plays pivotal roles in host antiviral innate immune responses, but an excessive production of type I IFN leads to the development of immunopathological conditions. Investigations on the regulatory mechanisms underlying host type I IFN production are currently of great interest. Here, we found that the expression of lectin family member Siglec1 was upregulated by viral infection in macrophages, which was dependent on the IFN/JAK/STAT1 signaling pathway.

MicroRNA-452 promotes tumorigenesis in hepatocellular carcinoma by targeting cyclin-dependent kinase inhibitor 1B.

Dysregulation of miR-452 has been observed in many tumors, but its biological function in hepatocellular carcinoma (HCC) is still unknown. Our results showed that miR-452 expression is significantly increased in HCC tissues and HCC cell lines. We also found that overexpression of miR-452 dramatically accelerated proliferation, induced cell cycle from G1 to S transition, and blocked apoptosis of HCC cells.

Molecular characterization and tissue localization of an F-box only protein from silkworm, Bombyx mori.

The eukaryotic F-box protein family is characterized by an F-box motif that has been shown to be critical for the controlled degradation of regulatory proteins. We identified a gene encoding an F-box protein from a cDNA library of silkworm pupae, which has an ORF of 1821 bp, encoding a predicted 606 amino acids. Bioinformatic analysis on the amino acid sequence shows that BmFBXO21 has a low degree of similarity to proteins from other species, and may be related to the regulation of cell-cycle progression.

Aligning the proteome and genome of the silkworm, Bombyx mori.

A technology of mass spectrometry (MS) was used in this study for the large-scale proteomic identification and verification of protein-encoding genes present in the silkworm (Bombyx mori) genome. Peptide sequences identified by MS were compared with those from an open reading frame (ORF) library of the B. mori genome and a cDNA library, to validate the coding attributes of ORFs.

Safety and immunogenicity of H5N1 influenza vaccine based on baculovirus surface display system of Bombyx mori.

Avian influenza virus (H5N1) has caused serious infections in human beings. This virus has the potential to emerge as a pandemic threat in humans. Effective vaccines against H5N1 virus are needed.

A novel method for isolation of membrane proteins: a baculovirus surface display system.

We have developed a novel baculovirus surface display (BVSD) system for the isolation of membrane proteins. We expressed a reporter gene that encoded hemagglutinin gene fused in frame with the signal peptide and transmembrane domain of the baculovirus gp64 protein, which is displayed on the surface of BmNPV virions. The expression of this fusion protein on the virion envelope allowed us to develop two methods for isolating membrane proteins.

Expression, purification and characterization of a three-domain Kazal-type inhibitor from silkworm pupae (Bombyx mori).

Serine protease inhibitors are essential for host physiological and immunological activities in insects. Analyzing the amino-acid sequence of a cDNA coding for a serine protease inhibitor in Bombyx mori (BmSPI), we found that BmSPI contained three homologous domains with a conserved sequence of C-X(3)-C-X(9)-C-X(6)-Y-X(7)-C-X(3)-C-X(11)-C similar to that of Kazal-type serine protease inhibitors, suggesting BmSPI as a new member of the Kazal-type serine protease inhibitor family. To characterize the three-domain Kazal-type inhibitor from silkworm pupae, the recombinant protein was expressed in Escherichia coli BL21 (DE3) Star.