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Maintaining homeostasis of the decidual immune microenvironment at the maternal–fetal interface is essential for placentation and reproductive success. Although distinct decidual immune cell subpopulations have been identified under normal conditions, systematic understanding of the spectrum and heterogeneity of leukocytes under recurrent miscarriage in human deciduas remains unclear. To address this, we profiled the respective transcriptomes of 18,646 primary human decidual immune cells isolated from patients with recurrent pregnancy loss (RPL) and healthy controls at single-cell resolution. We discovered dramatic differential distributions of immune cell subsets in RPL patients compared with the normal decidual immune microenvironment. Furthermore, we found a subset of decidual natural killer (NK) cells that support embryo growth were diminished in proportion due to abnormal NK cell development in RPL patients. We also elucidated the altered cellular interactions between the decidual immune cell subsets in the microenvironment and those of the immune cells with stromal cells and extravillous trophoblast under disease state. These results provided deeper insights into the RPL decidual immune microenvironment disorder that are potentially applicable to improve the diagnosis and therapeutics of this disease.

Problem Immune checkpoint molecules are receptors that can transmit inhibitory signals into cells to negatively modulate the immune response. However, their roles in NK cells during normal pregnancy remain poorly understood. Method of Study Peripheral blood samples were collected from women during the first, second and third trimesters of pregnancy. Peripheral blood NK (pNK) cells and T cells were analyzed for the expression of the immune checkpoint molecules TIGIT and PD-1 by flow cytometry. In addition, the ability of pNK cells to secret functional molecules was also evaluated. Results The expression of TIGIT on pNK cells increased gradually throughout pregnancy, whereas that of PD-1 showed the opposite pattern. However, on T cells, the expression of both TIGIT and PD-1 peaked during early pregnancy, and then declined gradually thereafter. Moreover, the expressions of granzyme B, IFN-γ and CD107a by pNK cells also decreased over the course of pregnancy. Compared with TIGIT- NK cells, TIGIT + NK cells possessed reduced expression of functional molecules. Conclusions As pregnancy progressed, the levels of immune checkpoint molecules expressed on pNK cells and T cells changed and the two molecules showed different trends. Furthermore, the secretion of functional molecules from pNK cells was negatively correlated with the trend of TIGIT expression, indicating TIGIT may play an important role in modulating the functions of pNK cells during pregnancy. Further study of TIGIT expression on pNK cells may enhance our understanding of its role in maintaining maternal-fetal tolerance and provide a useful marker for predicting instability during pregnancy.

Inflammasomes, intracellular, multimeric protein complexes, are assembled when damage signals stimulate nucleotide-binding oligomerization domain receptors (NLRs). Several inflammasomes have been reported, including the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), NLRP1, NLRP7, ice protease-activating factor (IPAF), absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4). Among these inflammasomes, the NLRP3 inflammasome is the most well-studied in terms of structure and function. Unlike other inflammasomes that can only be activated by a finite number of pathogenic microorganisms, the NLRP3 inflammasome can be activated by the imbalance of the internal environment and a large number of metabolites. The biochemical function of NLRP3 inflammasome is to activate cysteine-requiring aspartate proteinase-1 (caspase-1), which converts pro-IL-1β and pro-IL-18 into their active forms, namely, IL-1β and IL-18, which are then released into the extracellular space. The well-established, classic role of NLRP3 inflammasome has been implicated in many disorders. In this review, we discuss the current understanding of NLRP3 inflammasome and its critical role in gynecological disorders and obstetrical complications.

Among causes of infertility, teratozoospermia is characterised by a percentage of morphologically abnormal spermatozoa4%. Macrozoospermia, one form of monomorphic teratozoospermia, is observed in1% of cases of male infertility and is described as approximately 100% large-headed and/or multitailed spermatozoa. This study reports that an infertile man with large-head spermatozoa presenting compound heterozygosity aurora kinase C (AURKC) mutations (c.382CT, c.572CT) by whole-exome sequencing. Consequently, both two novel AURKC mutations had high probability of damage-causing and conserved across species and extremely low allele frequency in the population. Flow cytometry analysis revealed a high ratio of sperm DNA fragmentation. Two intracytoplasmic sperm injection (ICSI) procedures were attempted for the patient, but all were unsuccessful. These results indicate that sequence analysis should be performed for the variants of AURKC in Chinese patients with macrozoospermia.

IL-28B is a member of the newly discovered type III IFN family and exhibits unique antiviral properties compared with other family members. NK cells play a critical role in defending against viruses; however, little is known about the role of IL-28B in NK cell function. In a mouse model of influenza A virus (mouse adapted influenza A/PR/8/34 strain) infection, long-term overexpression of IL-28B induced by hepatocyte-specific gene delivery exerted a strong antiviral effect in the presence of NK cells. In IL-28B–overexpressing wild-type mice, the percentages and absolute numbers of NK cells in the spleen, liver, and lung were markedly increased, with higher proliferation and accelerated NK cell maturation based on phenotypes staining with CD11b and CD27 or CD11b and KLRG1. Furthermore, the effect of IL-28B on NK cells was macrophage dependent, as confirmed in an in vitro coculture assay and in in vivo macrophage- or alveolar macrophage–depletion experiments. Transwell studies demonstrated that CFSE-labeled NK cell proliferation was driven, in a dose-dependent manner, by unknown soluble factor(s) secreted by IL-28B–stimulated alveolar macrophages, without requiring direct cell–cell contact. An understanding of the NK cell–promoting features of IL-28B will facilitate future clinical application of this cytokine.

Objective To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV. Methods MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins. Results AS-IV reduced the proliferation of SW962 cells in a concentration- and time-dependent manner, induced cell-cycle arresting in G0/G1 phase, as demonstrated by the up-regulation of P53 and P21 expression, and the down-regulation of cyclin D1 expression. AS-IV enhanced the expression of Bax and cleaved-caspase 3, and suppressed Bcl-2 and Bcl-xl expression, which resulted in apoptosis increased. Furthermore, the expression of Beclin-1 and LC3-B was upregulated and that of P62 was downregulated, which suggested that AS-IV could increase the incidence of autophagy in SW962 cells. After inhibiting autophagy by 3-methyladenine (3-MA), cell apoptosis decreased upon AS-IV treatment. Similarly, TGF-β1 stimulated SW962 cells, cell proliferation enhanced, and the expression of TGF-βRII and Smad4 was decreased. Furthermore, the expression of proteins that promote apoptosis and autophagy decreased. After AS-IV treatment, the expression levels of the above proteins exhibited the opposite effect. Conclusion AS-IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF-β/Smad signaling pathway in VSCC.

Cervical cancer is one of the malignant tumors with high incidence and high mortality among women in developing countries. The main factors affecting the prognosis of cervical cancer are the late recurrence and metastasis and the effective adjuvant treatment, which is radiation and chemotherapy or combination therapy. Galectins, a family containing many carbohydrate binding proteins, are closely involved in the occurrence and development of tumor. They are involved in tumor cells transformation, angiogenesis, metastasis, immune escape, and sensitivity against radiation and chemotherapy. Therefore, galectins are deemed as the targets of multifunctional cancer treatment. In this review, we mainly focus on the role of galectins, especially galectin-1, galectin-3, galectin-7, and galectin-9 in cervical cancer, and provide theoretical basis for potential targeted treatment of cervical cancer.

Sleep patterns have been associated with the development of cancers, although the association between sleep duration and breast cancer remains controversial. The purpose of our study was to explore the relationship between sleep duration and breast cancer risk. The PubMed and Web of Science databases were searched, and restricted cubic splines were used to explore the dose-response relationship. Data from 415,865 participants were derived from 10 studies. A J-shaped nonlinear trend was found between sleep duration and breast cancer incidence (Pnon-linear= 0.012); compared with the reference hours (6 h or 7 h), with increasing sleep hours, the risk of breast cancer increased (Ptrend= 0.028). Moreover, a nonlinear relationship was found between sleep duration and estrogen receptor-positive breast cancer (Pnon-linear= 0.013); the risk of estrogen receptor-positive breast cancer increased with increasing sleep hours compared to the reference hours (Ptrend= 0.024). However, no nonlinear relationship was found between sleep duration and estrogen receptor-negative breast cancer; the risk of estrogen receptor-negative breast cancer was 1.035 for every additional sleep hour. Compared to women with the reference number of sleep hours, women with a longer sleep duration might have a significantly increased risk of breast cancer, especially estrogen receptor-positive breast cancer.

Interleukin-28A (IL-28A) modulates CD11c+ dendritic cell (DC) function and promotes type 1T helper (Th1) differentiation, thus suppressing allergic airway diseases. However, the function of the IL-28A isoform IL-28B in these diseases remains largely unknown. In this study, we revealed a novel role of IL-28B in inducing type 1 immunity and protecting against ovalbumin (OVA)-induced allergic asthma in mice. IL-28B overexpression in wild-type mice promoted natural killer (NK) cell polarization in the lung, leading to the increased number of interferon (IFN)-γ-producing NK1 cells as well as Th1 differentiation. Importantly, IL-28B overexpression had no protective effect on OVA-induced asthma in IFN-γ-knockout (IFN-γ−/−) mice. These results demonstrate that IL-28B ameliorates experimental allergic asthma via enhancing NK cell polarization, which might be useful for prevention and treatment of allergic asthma.