The role and challenges of regulating endometrial microbiome in uterine health and diseases.

The uterine environment provides necessary conditions for the existence of endometrial microbiota, which in turn plays an important role in maintaining the homeostasis of the uterine environment. The endometrial microbiome is highly susceptible to external factors such as age, hormones, menstrual, pregnancy, etc. When the microbiota is imbalanced, it will further promote the occurrence of uterine diseases such as endometritis and endometrial cancer. Regulating the microbiome of the endometrium is of positive significance for promoting uterine health. Among them, antibiotics, probiotics, prebiotics, and microbial transplantation may be important pathways for regulating endometrial microbiota in the future. However, there is currently no unified plan for evaluating the endometrial microbiota. In addition, due to the small sample size, it is easy to be contaminated by exogenous bacterial DNA, which poses great challenges for studying the mechanism of microbial community regulating uterine health. Therefore, there are still many areas worth exploring for the future of endometrial microbiome.

Luteolin attenuates Staphylococcus aureus-induced endometritis through inhibiting ferroptosis and inflammation via activating the Nrf2/GPX4 signaling pathway.

Endometritis, a local inflammatory disease, has been known as the most common cause of infertility in mares. In this study, we investigated the protective effects of luteolin on endometritis induced by Staphylococcus aureus (S. aureus) and further clarified the possible molecular mechanisms. An S. aureus-induced endometritis model was established by the infusion of S. aureus into the uterus. Luteolin was intraperitoneally administered to mice 1 h before S. aureus treatment. The results showed that the mice of the S. aureus group showed severe histological changes of uterine tissues, increased myeloperoxidase (MPO) activity, and elevated TNF-α, IL-1ß, and IL-6 levels. These changes induced by S. aureus were dose-dependently inhibited by luteolin. Furthermore, luteolin inhibited MDA and Fe2+ production and increased the production of GSH decreased by S. aureus. Luteolin prevented S. aureus-induced endometrial barrier disruption through up-regulating ZO-1 and occludin expression. Luteolin dramatically inhibited S. aureus-induced NF-κB activation. The expression of Nrf2 and HO-1 was increased by luteolin. In addition, the inhibitory effects of luteolin on S. aureus-induced endometritis were reversed in Nrf2 knockdown mice. In conclusion, these data indicated that luteolin protected mice against S. aureus-induced endometritis through inhibiting inflammation and ferroptosis via regulating the Nrf2 signaling pathway.IMPORTANCEEndometritis is an inflammatory disease of the endometrium, which is a common gynecological disease. Up to now, there is no evidence for the protective effects of luteolin on endometritis. The purpose of this study was to investigate whether luteolin has protective effects against S. aureus-induced endometritis and attempts to clarify the mechanism.

Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases.

The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and communication mode of MGB axis is crucial for understanding its role in diseases, and studying the signaling pathways and regulatory methods of MGB axis regulation in diseases is also of profound significance for future clinical research. This article reviews the composition, communication mechanism of MGB axis and its role in inflammatory and infective diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD), depression, psoriasis, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD). In addition, our investigation delved into the regulatory functions of the inflammasome, IFN-I, NF-κB, and PARK7/DJ-1 innate immune signaling pathway in the context of inflammatory and infective diseases. Ultimately, we discussed the efficacy of various interventions, including fecal microbiota transplantation (FMT), antibiotics, probiotics, prebiotics, synbiotics, and postbiotics, in the management of inflammatory and infective diseases. Understanding the role and mechanism of the MGB axis might make positive effects in the treatment of inflammatory and infective diseases.

Selenomethionine protects against Escherichia coli-induced endometritis by inhibiting inflammation and necroptosis via regulating the PPAR-γ/NF-κB pathway.

Endometritis, inflammation of the endometrium, is a major cause of subfertility in women. Selenomethionine (SeMet)is known to exert anti-inflammatory activity. We aimed to verify the protective roles of SeMet on Escherichia coli (E.coli)-induced endometritis. The extent of uterus damage was assessed by detecting histopathology and inflammatory mediators. The results revealed that SeMet significantly prevented E.coli-induced endometritis by attenuating uterine histopathology and inflammatory cytokine production. E.coli-induced MPO activity and MDA content were inhibited by SeMey. E.coli-induced ZO-1 and occludin were upregulated by SeMet. E.coli-induced necroptosis was also inhibited by SeMet. Additionally, E.coli-induced NF-κB activation was alleviated by SeMet. PPAR-γ expression was upregulated by SeMet. Notably, the protective effects of SeMet on endometritis were abolished by a PPAR-γ inhibitor. In conclusion, SeMet inhibits E.coli-induced endometritis by attenuating inflammation and necroptosis, which is mediated by the PPAR-γ/NF-κB signaling pathway.

Gut microbiota dysbiosis in polycystic ovary syndrome: Mechanisms of progression and clinical applications.

Polycystic ovary syndrome (PCOS) is the most common endocrine diseases in women of childbearing age that leads to menstrual disorders and infertility. The pathogenesis of PCOS is complex and has not yet been fully clarified. Gut microbiota is associated with disorders of lipid, glucose, and steroid hormone metabolish. A large body of studies demonstrated that gut microbiota could regulate the synthesis and secretion of insulin, and affect androgen metabolism and follicle development, providing us a novel idea for unravelling the pathogenesis of PCOS. The relationship between gut microbiota and the pathogenesis of PCOS is particularly important. This study reviewed recent research advances in the roles of gut microbiota in the occurrence and development of PCOS. It is expected to provide a new direction for the treatment of PCOS based on gut microbiota.

Protective effects of chicoric acid on LPS-induced endometritis in mice via inhibiting ferroptosis by Nrf2/HO-1 signal axis.

Chicoric acid (CA), a natural phenolic acid extracted from Mediterranean vegetable chicory, has anti-oxidative effect. We aimed to investigate the effects of CA on endometritis and clarify the underlying mechanism. C57BL/6 mice were divided into five groups: control group, LPS group, and LPS + CA groups. All mice except control group were infused of LPS into the uterus. The mice of LPS + CA groups were intraperitoneally injected CA 1 h before LPS challenge. CA significantly alleviatedLPS-induced pathological damage, MPO activity, and inflammatory cytokine production. CA significantly suppressed ferroptosis in LPS-induced endometritis. CA also attenuated LPS-induced NF-κB activation. Furthermore, Nrf2 and HO-1 expression were increased by CA. Moreover, the inhibition of CA on LPS-induced endometritis and ferroptosis were markedly prevented in Nrf2 knockdown mice. In conclusion, the results suggested CA protected mice against LPS-induced endometritisthrough inhibiting ferroptosis via Nrf2/HO-1 signaling pathway.

Hemorrhagic shock caused by primary splenic pregnancy with spontaneous splenic rupture.

The subject, splenic pregnancy, is very rare and interesting with about a few cases reported to date. This case report describes a healthy 17-year-old girl admitted to our hospital who complained of amenorrhea for 30 days, intermittent abdominal pain for 3 days and worsening for 1 h. The serum human chorionic gonadotropin (hCG) was greater than 10000.0 IU/L. Pelvic ultrasonography showed a adnexal mass and empty uterine cavity. Due to consideration of "ectopic pregnancy," emergency laparoscopic surgery was performed. However, no clear lesions and bleeding points were detected during the operation. On postoperative day 2, hemoglobin level dropped sharply, meanwhile serum hCG increased significantly. Subsequent ultrasound showed a 4.4 × 4.1 × 2.6 cm gestational sac-like echo below the spleen. Laparotomy detected pregnancy tissues measured 4.0 × 3.5 cm next to the splenic hilum. Finally, the splenectomy was performed. Our case suggests that early diagnosis of splenic pregnancy is very difficult, especially when other conditions are combined. Despite this, we should still enrich ourself medical knowledge and clinical experience, and try to avoid the occurrence of splenic rupture.

Astragaloside IV antagonizes M2 phenotype macrophage polarization-evoked ovarian cancer cell malignant progression by suppressing the HMGB1-TLR4 axis.

Macrophages are the most abundant cells in tumor stroma and their polarization within tumor microenvironment exert the key roles in tumorigenesis. Astragaloside IV is a natural extract from traditional Chinese herbal Radix Astragali, and fulfills pleiotropic function in several cancers. Nevertheless, its function in ovarian cancer microenvironment remains elusive. In the present research, astragaloside IV exhibited little cytotoxicity within a certain dose range in THP-1 cells. Moreover, astragaloside IV suppressed the ratio of CD14+CD206+ cells in IL-4/IL-13-treated THP-1 macrophages and transcripts of M2 macrophage markers (including CD206, CCL24, PPARγ, Arg-1, IL-10), indicating the inhibitory effects of astragaloside IV on IL-4/IL-13-induced macrophage M2 polarization. Intriguingly, astragaloside IV antagonized M2 macrophages coculture-evoked cell proliferation, invasion and migration in ovarian cancer cells. During this process, administration with astragaloside IV restrained the high expression of high-mobility group box1 (HMGB1) and TLR4 in macrophages co-cultured with ovarian cancer cells, concomitant with decreases in release of M2 marker TGF-ß, MMP-9 and IL-10. Moreover, targeting the HMGB1 signaling reversed M2 macrophages-induced ovarian cancer cell proliferation, invasion and migration. Noticeably, exogenous HMGB1 overturned the inhibitory efficacy of astragaloside IV against macrophage M2 polarization-evoked malignant potential in ovarian cancer cells. Together, these findings suggest that astragaloside IV may protect against M2 macrophages-evoked malignancy in ovarian cancer cells by suppressing the HMGB1-TLR4 signaling. Therefore, astragaloside may alleviate the progression of ovarian cancer by regulating macrophage M2 polarization within tumor microenvironment, implying a promising therapeutic strategy against ovarian cancer.

Long non-coding RNA FEZF1-AS1 induced progression of ovarian cancer via regulating miR-130a-5p/SOX4 axis.

Emerging studies have revealed the critical role of long non-coding RNAs (lncRNAs) in epithelial ovarian cancer (EOC) development and progression. Till now, the roles and potential mechanisms regarding FEZF1 antisense RNA 1 (FEZF1-AS1) within ovarian cancer (OC) remain unclear. The objective of this study was to uncover the biological function and the underlying mechanism of LncRNA FEZF1-AS1 in OC progression. FEZF1-AS1 expression levels were studied in cell lines and tissues of human ovarian cancer. In vitro studies were performed to evaluate the impact of FEZF1-AS1 knock-down on the proliferation, invasion, migration and apoptosis of OC cells. Interactions of FEZF1-AS1 and its target genes were identified by luciferase reporter assays. Our data showed overexpression of FEZF1-AS1 in OC cell lines and tissues. Cell migration, proliferation, invasion, wound healing and colony formation were suppressed by silencing of FEZF1-AS1. In contrast, cell apoptosis was promoted by FEZF1-AS1 knock-down in vitro. Furthermore, online bioinformatics analysis and tools suggested that FEZF1-AS1 directly bound to miR-130a-5p and suppressed its expression. Moreover, the inhibitory effects of miR-130a-5p on the OC cell growth were reversed by FEZF1-AS1 overexpression, which was associated with the increase in SOX4 expression. In conclusion, our results revealed that FEZF1-AS1 promoted the metastasis and proliferation of OC cells by targeting miR-130a-5p and its downstream SOX4 expression.