Prunella stica inhibits the proliferation but not the prostaglandin production of Ishikawa cells

Chinese herbs have been used to relieve dysmenorrhea associated with endometriosis. Active components in the herbs and their mechanisms of action remain unknown. Prunella stica, a Chinese herb commonly used to treat dysmenorrhea, was chosen for the present studies. Its effects were investigated on Ishikawa cells, an epithelial cell line derived from human endometrium. Cell proliferation and inhibition of interleukin 1beta (IL-1beta) induced prostaglandin (PG) production were examined. To learn more about the active components, 120 fractions were collected from the crude extract and each fraction was tested individually. To further characterize the active components, aliquots of fractions with activity were subject to mass spectrometry analysis. Crude extract of P. stica inhibited the proliferation of Ishikawa cells but not the IL-1beta induced PG production. Active components of P. stica clustered around fractions 64 and 92; they increased cell doubling time from 18.6 to 26.2 and 29.4h, respectively. Mass spectrometry analysis showed fractions 64 and 92 consisted of three components whose molecular weights were 337, 348 and 430 Daltons. The therapeutic effects of P. stica reside, in part, in inhibiting the proliferation of the epithelial cells derived from human endometrium. The active components are small molecules.     

In vivo analysis of progesterone receptor action in the uterus during embryo implantation

In order for a successful pregnancy to occur, the embryo must attach to the luminal epithelial cells and invade into the stroma. Then, the surrounding stromal cells need to undergo decidualization in order to establish the vasculature necessary for survival of the embryo. These events in early pregnancy are tightly regulated by the steroid hormones, estrogen (E2) and progesterone (P4), through their cognate receptors, the estrogen receptor (ER) and the progesterone receptor (PR), respectively. Using a mouse model in which the PR has been ablated, it was demonstrated that the PR is necessary for embryo implantation and decidualization. Therefore, understanding the mechanism of PR action in the adult uterus is necessary in order to understand the events of early pregnancy. Insights from both mouse models and human samples have been integral in elucidating uterine PR action. These studies have shown that not only PR target genes, but also mediators of PR action are important for correct PR action in early pregnancy. Many of the genes involved in PR action in early pregnancy have also been shown to have roles in uterine diseases such as endometriosis and endometrial cancer. Therefore, the integration of mouse and human studies on PR action in the uterus will be important for the future understanding of uterine diseases and in the development of treatment for these diseases.     

Spatial and temporal characterization of endometrial mesenchymal stem-like cells activity during the menstrual cycle

The human endometrium is a highly dynamic tissue with the ability to cyclically regenerate during the reproductive life. Endometrial mesenchymal stem-like cells (eMSCs) located throughout the endometrium have shown to functionally contribute to endometrial regeneration. In this study we examine whether the menstrual cycle stage and the location in the endometrial bilayer (superficial and deep portions of the endometrium) has an effect on stem cell activities of eMSCs (CD140b⁺CD146⁺ cells). Here we show the percentage and clonogenic ability of eMSCs were constant in the various stages of the menstrual cycle (menstrual, proliferative and secretory). However, eMSCs from the menstrual endometrium underwent significantly more rounds of self-renewal and enabled a greater total cell output than those from the secretory phase. Significantly more eMSCs were detected in the deeper portion of the endometrium compared to the superficial layer but their clonogenic and self-renewal activities remained similar. Our findings suggest that eMSCs are activated in the menstrual phase for the cyclical regeneration of the endometrium.     

Reproduction and life history strategies of the common jellyfish, Aurelia aurita, in relation to its ambient environment

The scyphozoan Aurelia aurita (Linnaeus) is a cosmopolitan species, having been reported from a variety of coastal and shelf sea environments around the world. It has been extensively studied over the last 100 years or so, and examination of the literature reveals three striking features: (1) the presence of populations in a wide range of environmental conditions; (2) large inter-population differences in abundance and life history patterns over large and small spatial scales; and (3) inter-annual variability in various aspects of its population dynamics. A. aurita is clearly a highly flexible species that can adapt to a wide range of environmental conditions. While various physiological and behavioural characteristics explain how A. aurita populations can take advantage of their surrounding environment, they do not explain what governs the observed temporal and spatial patterns of abundance, and the longevity or lifespan of populations. Understanding these features is necessary to predict how bloom populations might form. In a given habitat, the distribution and abundance of benthic marine invertebrates have been found to be maintained by four factors: larval recruitment (sexual reproduction), migration, mortality and asexual reproduction. The aims of this review are to determine the role of reproduction and life history strategies of the benthic and pelagic phases of A. aurita in governing populations of medusae, with special attention given to the dynamic interaction between A. aurita and its surrounding physical and biological environment.     

Effects of low dissolved oxygen on survival and asexual reproduction of scyphozoan polyps (Chrysaora quinquecirrha)

Hypoxic conditions are common in many coastal environments such as Chesapeake Bay. While medusae appear to be quite tolerant of low dissolved oxygen (DO) concentrations, the effects of hypoxia on the benthic polyp stages are unknown. Chrysaora quinquecirrha (DeSor) polyps, and were subjected to 5 DO treatments (air-saturated [control], 3.5, 2.5, 1.5 and 0.5 mg l^–1) in the laboratory. Polyp survival and development were documented over 24 d. Virtually no mortality occurred in any treatment during the first 5 d. Total polyp mortality after 24 d was 59.3% at the lowest DO concentration, whereas <3% mortality was observed in the air-saturated treatment. Formation of stolons and strobilae occurred in all treatments, however, the proportions of polyps undergoing stolonation and strobilation were significantly greater in all DO concentrations above 0.5 mg l^–1. Polyp encystment was not observed in any treatment over the course of the 24 d experiment. These results indicate that polyps can survive and asexually propagate even during prolonged exposure to hypoxic conditions.     

Long-chain glucosylceramides crosstalk with LYN mediates endometrial cell migration

Endometriosis is a disease characterized by regurgitated lesions which are invasive and migratory, embedding at ectopic, extra-uterine locations. Extracellular glucosylceramides (GlcCers), bioactive sphingolipids potentiating signals for cell migration, are found in elevated levels in endometriosis; however underlying mechanisms that result in cellular migration are poorly defined. Here, we demonstrated that internalized GlcCer induced migratory activity in immortalized human endometrial stromal cells (HESCs), with highest potency observed in long-chain GlcCer. Long-chain ceramide (Cer) similarly induced cellular migration and mass spectrometry results revealed that the migratory behavior was contributed through glycosylation of ceramides. Cells treated with GlcCer synthase inhibitor, or RNAi-mediated knockdown of glucosylceramide synthase (GCS), the enzyme catalyzing GlcCer production attenuated cell motility. Mechanistic studies showed that GlcCer acts through stromal cell-derived factor-1 alpha and its receptor, CXC chemokine receptor 4 (SDF-1α-CXCR4) signaling axis and is dependent on phosphorylation of LYN kinase at Tyr396, and dephosphorylation of Tyr507. Migration was prominently attenuated in cells exposed to CXCR4 antagonist, AMD3100, yet can be rescued with diprotin A, which prevents the degradation of SDF-1α. Furthermore, blocking of LYN kinase activity in the presence of SDF-1α and GlcCer reduced HESC migration, suggesting that LYN acts downstream of GlcCer-SDF-1α-CXCR4 axis as part of its intracellular signal transduction. Our results reveal a novel role of long-chain GlcCer and the dialog between GlcCer, LYN^pTyr396 and SDF-1α-CXCR4 in inducing HESC migration. This finding may improve our understanding how endometriotic lesions invade to their ectopic sites, and the possibility of using GlcCer to modulate the SDF-1α-CXCR4-LYN^pTyr396 axis in endometriosis.     

加减黄芪丹参饮联合优思悦治疗多囊卵巢综合征的效果及对外周血Th17/Treg免疫失衡的影响研究

摘要 目的：探讨与研究加减黄芪丹参饮联合优思悦治疗多囊卵巢综合征的效果及对外周血Th17/Treg免疫失衡的影响。方法：选择2018年7月到2022年1月在本院诊治的多囊卵巢综合征患者66例作为研究对象,根据1:1简单分配原则把患者分为中药组与对照组各33例。对照组给予优思悦治疗,中药组在对照组治疗的基础上给予加减黄芪丹参饮治疗,所有患者都治疗观察3个月经周期,测定与计算外周血Th17/Treg免疫失衡情况。结果：治疗后中药组的总有效率为100.0%,与对照组的81.8%相比明显增高（P<0.05）。两组治疗后的Th17/Treg值都明显低于治疗前（P<0.05）,中药组与对照组相比也明显降低（P<0.05）。两组治疗后的子宫内膜厚度与最大卵泡直径都明显高于治疗前（P<0.05）,治疗后中药组与对照组相比也明显提高（P<0.05）。两组治疗后的血清雌二醇(E₂)含量明显高于治疗前（P<0.05）,血清催乳素（PRL）含量明显低于治疗前（P<0.05）,治疗后中药组与对照组都有明显差异差异（P<0.05）。结论：加减黄芪丹参饮联合优思悦治疗多囊卵巢综合征能有效调节外周血Th17/Treg免疫失衡,促进性激素分泌正常,提高患者的子宫内膜厚度与最大卵泡直径,提高患者的总体治疗效果。     

KANK1对子宫内膜癌细胞增殖及迁移的影响

摘要 目的：研究KANK1在子宫内膜癌中的表达以及对子宫内膜癌细胞增殖及迁移的影响。方法：（1）TCGA数据库分析KANK1在子宫内膜癌中的表达和生存期分析。（2）采用实时荧光定量聚合酶链反应验证转染KANK1质粒的效果。采用Ishikawa和ECC1这两种子宫内膜癌细胞来探讨KANK1对子宫内膜癌的细胞周期和凋亡的影响。通过Western blot检测细胞周期相关蛋白的表达,以及流式细胞术检测细胞周期和凋亡水平。（3）通过Transwell小室实验和划痕实验检测细胞的侵袭和转移能力。结果：TCGA数据库分析发现KANK1在子宫内膜癌中低表达且与患者预后良好相关。过表达KANK1下调了Cyclin D1和Cyclin D2的蛋白水平,并将细胞周期阻滞在G1期。流式细胞术检测发现过表达KANK1组的细胞凋亡水平（Ishikawa：22.7%;ECC1：19.0%）比对照组（Ishikawa：18.1%;ECC1：15.3%）高,差异具有统计学意义。Transwell迁移和侵袭实验结果表明过表达KANK1组的子宫内膜癌细胞侵袭和转移能力减弱。结论：本研究证明了KANK1在子宫内膜癌中发挥抑癌作用。KANK1高表达与子宫内膜癌的预后良好成正相关。KANK1通过抑制癌细胞周期和促进肿瘤细胞凋亡发挥抑制子宫内膜癌增殖的作用。此外,KANK1抑制了子宫内膜癌的侵袭和转移。     

Incidence of gynaecological cancer during the COVID-19 pandemic: A population-based study in the Netherlands

ObjectiveTo study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands.MethodsWe performed a retrospective cohort study using data from the Netherlands Cancer Registry (NCR) on women of 18 years and older diagnosed with invasive endometrial, ovarian, cervical or vulvar cancer in the period 2017–2021. Analyses were stratified for age, socioeconomical status (SES) and region.ResultsThe incidence rate of gynaecological cancer was 67/100.000 (n = 4832) before (2017–2019) and 68/100.000 (n = 4833) during (2020) the COVID-19 pandemic. Comparing the number of diagnoses of the two periods for the four types of cancer separately showed no significant difference. During the first wave of COVID-19 (March-June 2020), a clear decrease in number of gynaecological cancer diagnoses was visible (20–34 %). Subsequently, large increases in number of diagnoses were visible (11–29 %). No significant differences in incidence were found between different age groups, SES and regions. In 2021 an increase of 5.9 % in number of diagnoses was seen.ConclusionIn the Netherlands, a clear drop in number of diagnoses was visible for all four types of gynaecological cancers during the first wave, with a subsequent increase in number of diagnoses in the second part of 2020 and in 2021. No differences between SES groups were found. This illustrates good organisation of and access to health care in the Netherlands.     

Nucleolar organizer regions in the normal,hyperplastic and carcinomatous epithelium of endometrium

A silver colloid technique to identify nucleolar organizer region associated protein (AGNORs) has been applied to paraffin sections in a total of 43 endometrial hyperplasias (24 adenomatous and 19 adenocystic) 26 endometrial carcinomas and 22 normal endometria (11 of proliferative and 11 of secretory phase). A morphometric analysis of highly magnified photographic images of AGNORs in light microscopic preparations was performed. Malignant tumor cells showed significantly higher AGNOR numbers, maximum diameter and mean area compared with normal and hyperplastic endometrium, with the exception of adenocystic hyperplasia whose D_max and mean area were significantly larger. Regarding the distribution pattern of AGNOR dots in the cases studied, it was found that normal and hyperplastic endometrium had a mainly clustered distribution while endometrial adenocarcinomas revealed a scattered one. The significant differences observed in the number of AGNORs, their size and mean area between benign and malignant endometrial epithelia suggest that the AG-NOR staining technique is of diagnostic importance in distinguishing between these two groups.