Exposure to higher concentrations of exogenous ELABELA causes HTR-8/SVneo trophoblast cell dysfunction: A possible pathogenesis of pre-eclampsia.

Pre-eclampsia (PE) is a multi-system disorder of pregnancy which constitute one of the leading causes of maternal and perinatal mortality worldwide. Dysfunction of trophoblast cells have been play an a significant role in the development and progression of PE. ELABELA (ELA), an endogenous apelin receptor (APJ) ligand, is a hormone secreted by the placenta into circulation, we previously identified ELA and its cognate apelin receptor (APJ) as proteins that are differentially expressed in the placentas of humans with PE. However, a fact known to few about the potential regulatory effects of ELA on the functions of trophoblast cells. In this study, our experiments showed that exogenous ELA did not effectively affect the proliferation and apoptosis of HTR-8/SVneo cells in higher concentrations but inhibited the invasion and migration capabilities. Studies have shown that the epithelial-mesenchymal transition (EMT) event of trophoblast cells is abnormal through regulate the P13K/AKT pathway in PE. First we confirmed APJ expression in HTR-8/SVneo cells and ELA suppressed P13K/AKT signalling pathway-related factors (AKT, phospho (p)-AKT) phosphorylation in HTR-8/SVneo cells in a concentration-dependent manner. Next, we found that treatment with higher concentrations of ELA or the P13K inhibitor LY294002 significantly increased the expression of ß-catenin which is the classical epithelial marker relative to the control group. Moreover, treatment with both LY294002 and ELA more strongly affected the ß-catenin expression and the HTR8/SVneo cells invasion and migration. These results demonstrate that ELA inhibits trophoblast cell functions by altering the ß-catenin expression get though the PI3K/AKT signalling pathway in PE. Thus, this result might provide a new therapeutic target for the treatment of PE.

Nine Pyroptosis-Related lncRNAs are Identified as Biomarkers for Predicting the Prognosis and Immunotherapy of Endometrial Carcinoma.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common malignancies. Immunotherapy has shown promising effects in the treatment against specific subtypes of EC. METHODS: The RNA and clinical information of patients with EC were acquired from The Cancer Gene Atlas (TCGA) database. Firstly, the differentially expressed pyroptosis-related lncRNAs (PRLs) were screened between the tumor and normal control tissue. Secondly, the PRLs closely related to survival were identified by univariate and multivariate regression analysis, based on which, we evaluated the risk score for each EC patient to construct a risk signature. Moreover, we assessed the prognostic value, clinical relevance immunity, and immunotherapy based on this signature. RESULTS: We screened out 9 individual PRLs (AC087491.1, AL353622.1, AL035530.2, LINC02036, AL021578.1, AL390195.2, AC009097.2, AC004585.1, and AC244517.7) closely related to the prognosis of EC. Kaplan-Meier analyses showed a poorer prognosis for the patients in the high-risk FRLs signature (P < 0.001). The area under the curve (AUC) for 1 year, 2 years, 3 years was 0.693, 0.694, 0.750, respectively. Our risk model could be considered as an independent prognostic marker for EC (P < 0.001, HR:2.172, 95% CI:1.532-3.079). Moreover, immune functions and checkpoints were generally different in the 2 groups. Simulation analysis by termed immunophenoscores hinted that immunotherapy might bring optimal therapeutic effect in the low-risk group. CONCLUSION: We successfully developed a novel signature with 9 lncRNAs related to pyroptosis, which may be used as biomarkers to evaluate the prognosis and immune treatment of EC.

Comparison of thermal ablative methods and myomectomy for the treatment of fibroids: a systematic review and meta-analysis.

OBJECTIVE: To examine the effectiveness and safety of thermal ablative methods and myomectomy for the treatment of uterine fibroids. MATERIALS AND METHODS: We searched EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, Scopus, CINAHL, ClinicalTrials.gov and Web of Science databases through April 2021. Clinical trials comparing the thermal ablative methods and myomectomy for the treatment of uterine fibroids were included. RESULTS: Thirteen studies including 4205 patients were eligible. The thermal ablative treatment group was associated with less major adverse events (only ultrasound guided high-intensity focused ultrasound) (RR, 0.111 [95% CI, 0.070-0.175], p=.0), shorter duration of hospital stays in observational studies (-0.1497 day, [95% CI, -1.593 to -0.321], p=.0) and in randomized controlled trials (RCTs) (-0.844 day, [95% CI, -0.1.142 to -0.546], p=.0), higher uterine fibroid symptom (UFS) score after operation (0.252 [95% CI, 0.165-0.339]; p=.0), transformed symptom severity (tSS) score after operation (0.515 [95% CI, 0.355-0.674]; p=.0) and quality of life (QoL) score after operation (0.188 [95% CI, 0.093-0.283]; p=.0) in comparison with myomectomy group. No statistically significant difference was found between the thermal ablative treatment group and myomectomy group with respect to reintervention rate and pregnancy rate. CONCLUSION: The current data available demonstrate that thermal ablative methods were not inferior to myomectomy in the treatment of uterine fibroids. The findings in this study need to be further confirmed by large RCTs.

Internal iliac artery balloon occlusion in the management of placenta accreta: A systematic review and meta-analysis.

PURPOSE: To examine the effectiveness and safety of prophylactic internal iliac artery balloon occlusion for hemorrhage control in placenta accreta. METHOD: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials data-bases were searched through November 2020. Clinical trials comparing the management of placenta accreta with and without internal iliac artery balloon occlusion were included. The meta-analysis results were expressed as the risk ratio (RR) or mean difference, with 95 % CIs. RESULTS: Fifteen studies including 1098 women were eligible. No statistically significant difference was found between the internal arterial balloon occlusion group and the control group with respect to estimated blood loss volume (-0.525 mL, [95 % CI, -1.112 to -0.061], p = 0.079.), red blood cells (RBCs) transfused in observational studies (-0.682 mL, [95 % CI, -1.540 to 0.176], p = 0.119.) and in randomized controlled trials (0.134 mL, [95 % CI, -0.214 to 0.482], p = 0.451.), intensive care unit admission (p = 0.197), hysterectomy in observational studies (p = 0.969) and in randomized controlled trials (p = 0.323), urinary system injury in observational studies (p = 0.182) and in randomized controlled trials (p = 0.956), Apgar score at 5 min (p = 0.641), and neonatal intensive care unit admission (p = 0.973). CONCLUSIONS: The currently available data demonstrate no significant differences between the internal iliac artery balloon occlusion group and the control group in blood loss and packed RBCs transfused for women with placenta accreta. Further large randomized controlled studies are needed to confirm our findings.

Chronic overload of concentration-dependent iron exerts different effects on ovarian function in C57BL/6J mice†.

Overloaded iron can deposit in the reproductive system and impair ovarian function. But few studies have identified the exact effect of overloaded iron on the endocrine function and fertility capacity in female mice. Here, we established iron-overloaded mouse models by intraperitoneal injection of iron dextran to adult female C57BL/6J mice at 0.1 g/kg (LF group), 0.5 g/kg (MF group), and 1.0 g/kg (HF group) concentrations once a week for eight consecutive weeks. We found that overloaded iron resulted in smaller ovaries, as well as accumulated oxidative damages. The endocrine function and follicle development were also impeded in the MF and HF groups. The 10-month breeding trial indicated that (1) Low concentration of iron (0.1 g/kg) wasn't detrimental to the ovary; (2) Middle concentration of iron (0.5 g/kg) impeded the childbearing process, though it could be recovered following the iron excretion; and (3) High concentration of iron (1.0 g/kg) damaged the fertility, even gave rise to sterility. Yet for those fertile mice, litter number and litter size were smaller and the ovarian reserve of their offspring was impaired. Transcriptome profiling results indicated that overloaded iron could compromise ovarian function by disrupting ovarian steroidogenesis, interfering with ovarian microenvironment, and inhibiting Wnt signaling. Taken together, we have demonstrated the effect that chronic concentration-dependent iron overload exerted on mouse ovarian function, which may act as a preliminary basis for further mechanism and intervention investigations.

Comparative study of placental α-microglobulin-1, insulin-like growth factor binding protein-1 and nitrazine test to diagnose premature rupture of membranes: a randomized controlled trial.

AIM: The aim of this study was to compare the accuracy of placental α-microglobulin-1 (PAMG-1), insulin-like growth factor binding protein-1 (IGFBP-1) and nitrazine test to diagnose premature rupture of membranes. MATERIAL AND METHODS: A total of 120 pregnant women between 11 and 42 weeks with signs/symptoms of membrane rupture were eligible for our study. These women were evaluated with the PAMG-1, IGFBP-1, and nitrazine tests. RESULTS: In the 120 women, the sensitivity, specificity, positive predictive value, and negative predictive value of PAMG-1, IGFBP-1 and nitrazine test were 100%, 100%, 100%, and 100%, 93.33%, 98.89%, 96.55% and 97.80%, and 93.33%, 94.44%, 84.85%, and 97.7%, respectively. In a comparison of the PAMG-1 test and the nitrazine test, positive coincidence rate was 84.85%, negative coincidence rate was 97.70%, total coincidence rate was 94.17%, and kappa value was 0.85. In a comparison of the PAMG-1 test and the IGFBP-1 test, the positive coincidence rate, negative coincidence rate and total coincidence rate were 96.55%, 97.80%, and 97.50%, and kappa value was 0.93. CONCLUSION: PAMG-1 assay was the most accurate method to diagnose premature rupture of membranes with the highest sensitivity, specificity, positive predictive value and negative predictive value.