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Abstract Background This study aimed to analyze the impact of preoperative cervical length before cervical cerclage on the extension of gestational days in patients with various diagnostic types of cervical insufficiency, including obstetric history-based diagnosis, ultrasound-based diagnosis, and physical examination-based diagnosis. Methods 168 patients were segregated into four categories based on cervical length: 0–0.4 cm, 0.5–1.4 cm, 1.5–2.4 cm, and ≥ 2.5 cm. Kaplan-Meier, linear regression curve and Cox regression analyses were used, with a focus on clinical variables, particularly cervical length and the duration of extension after cervical cerclage. Results The length of the cervix prior to cervical cerclage correlated with the prognosis of 168 postoperative patients by linear regression analysis. When delivery beyond 28 or 34 weeks was set as the primary prognostic indicator, univariate Cox analysis showed that postoperative C-reactive protein (CRP) level was identified as a risk factor for gestational age extension in cervical cerclage patients. Longer cervical length was identified as a protective factor for overall gestational age extension in cervical cerclage patients. In addition, the obstetrical-history diagnosis group had a better prognosis compared to the emergency cerclage group, which had a worse prognosis compared to the ultrasound-based diagnosis group. Kaplan-Meier curve analysis of all patients revealed a statistically significant impact of different cervical lengths on the gestational age of delivery (P

Abstract Background Ovarian cancer (OC) has the highest mortality rate among all gynecological malignancies. A hypoxic microenvironment is a common feature of solid tumors, including ovarian cancer, and an important driving factor of tumor cell survival and chemo- and radiotherapy resistance. Previous research identified the hypoxia-associated gene angiopoietin-like 4 (ANGPTL4) as both a pro-angiogenic and pro-metastatic factor in tumors. Hence, this work aimed to further elucidate the contribution of ANGPTL4 to OC progression. Methods The expression of hypoxia-associated ANGPTL4 in human ovarian cancer was examined by bioinformatics analysis of TCGA and GEO datasets. The CIBERSORT tool was used to analyze the distribution of tumor-infiltrating immune cells in ovarian cancer cases in TCGA. The effect of ANGPTL4 silencing and overexpression on the proliferation and migration of OVCAR3 and A2780 OC cells was studied in vitro, using CCK-8, colony formation, and Transwell assays, and in vivo, through subcutaneous tumorigenesis assays in nude mice. GO enrichment analysis and WGCNA were performed to explore biological processes and genetic networks associated with ANGPTL4. The results obtained were corroborated in OC cells in vitro by western blotting. Results Screening of hypoxia-associated genes in OC-related TCGA and GEO datasets revealed a significant negative association between ANGPTL4 expression and patient survival. Based on CIBERSORT analysis, differential representation of 14 distinct tumor-infiltrating immune cell types was detected between low- and high-risk patient groups. Silencing of ANGPTL4 inhibited OVCAR3 and A2780 cell proliferation and migration in vitro and reduced the growth rate of xenografted OVCAR3 cells in vivo. Based on results from WGCNA and previous studies, western blot assays in cultured OC cells demonstrated that ANGPTL4 activates the Extracellular signal-related kinases 1 and 2 (ERK1/2) pathway and this results in upregulation of c-Myc, Cyclin D1, and MMP2 expression. Suggesting that the above mechanism mediates the pro-oncogenic actions of ANGPTL4T in OC, the pro-survival effects of ANGPTL4 were largely abolished upon inhibition of ERK1/2 signaling with PD98059. Conclusions Our work suggests that the hypoxia-associated gene ANGPTL4 stimulates OC progression through activation of the ERK1/2 pathway. These findings may offer a new prospect for targeted therapies for the treatment of OC.

Abstract Background Ovarian cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian cancer is still unknown. Aims The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian cancer. Materials and Methods We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co‐immunoprecipitation and western blotting. Results TRIM8 was overexpressed in ovarian cancer. TRIM8 promoted the proliferation and migration of ovarian cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian cancer progression induced by TRIM8 overexpression. Discussion TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian cancer. Conclusion TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian cancer cells to iron death, and promoted the proliferation and migration of ovarian cancer.

Introduction: Cervical insufficiency is an increased risk of midterm miscarriage and early preterm birth which increase the risk of fetal loss. This study aimed to construct a nomogram for patients with cervical insufficiency after cervical cerclage, which may assist clinicians to have individualized treatment for patients with cervical insufficiency. Methods: A study was done retrospectively from January 2013 through July 2022 in our hospital. The primary outcomes were delivered at more than 28, 30, 32, or 34 gestational weeks. Kaplan-Meier curves were applied to analyze 17 variables. All patients were randomly split (147:64) into development and validation cohorts. Based on the multivariate Cox regression analysis, a nomogram was constructed through the 'rms' package in R. Results: A total of 211 patients with cervical insufficiency were enrolled: 121 had history-indicated cerclage; 58 had ultrasound-indicated cerclage and 32 had emergency cerclage. Times of gestations, times of miscarriages, IVF, abdominal pain, diagnostic classification, preoperative and postoperative management were demonstrated to impact overall extended days when delivering at more than 28 gestational weeks was set as the primary outcome. Except for preoperative and postoperative management, the above other five variables impacted the primary outcomes of delivering at more than 30, 32, or 34 gestational weeks. Postoperative tocolytics had an impact on the prognosis of patients who delivered at more than 30 gestational weeks. In development cohort data, a nomogram was established to predict overall extended days of patients with cervical cerclage. In present study, C-index was 0.662 in the development cohort and 0.687 in the validation cohort respectively, suggesting that the model presented some satisfied prediction. Moreover, the clinical decision curves for patients with delivering at more than 28, 30, 32 or 34 weeks set as primary outcomes also displayed that this nomogram demonstrated good clinical predictive usefulness. Conclusions: The nomogram developed in this study may be a valuable tool assisting clinicians to evaluate outcomes of patients with cervical insufficiency after cervical cerclage, which helps them develop individualized management for the patients.

Abstract Background Spontaneous abortion is considered as the commonest complication of pregnancy. Triclosan (TCS) is an antimicrobial agent, which participates in the process of multiple human diseases, including spontaneous abortion. Our study aimed to evaluate the effect of TCS on spontaneous abortion and disclose the possible regulatory mechanism in vitro. Results RT-qPCR analyzed that miR-218-1-3p derived from abortion-associated factor slit guidance ligand 2 (SLIT2) was up-regulated in trophoblast cells under TCS treatment. Supported by western blot analysis, functional experiments demonstrated that miR-218-1-3p overexpression impeded the proliferation, migration and invasion while exacerbating the inflammatory response of trophoblast cells. Moreover, mechanism assays revealed that TCS modulated c-Jun production to promote MIR218–1 transcription and enhance miR-218-1-3p expression. Moreover, solute carrier family 35 member C1 (SLC35C1) was validated as a target gene of miR-218-1-3p, and miR-218-1-3p was sustained to negatively modulate SLC35C1 expression in trophoblast cells. Rescue assays validated the role of TCS/miR-218-1-3p/SLC35C1 axis in regulating the viability, migration, invasion and inflammatory response of trophoblast cells. Conclusions TCS regulated miR-218-1-3p/SLC35C1 axis to modulate the proliferation, migration, invasion and inflammatory response of trophoblast cells in vitro, which might provide novel insights for spontaneous abortion prevention. Graphical Abstract

Human amniotic mesenchymal stem cells (hAMSCs) were previously shown to effectively rescue ovarian function in a premature ovarian insufficiency (POI) mouse model. The therapeutic mechanism of hAMSC-derived exosomes (hAMSC-Exos) is not fully understood. In this study, the therapeutic mechanism involved in exosomal microRNA-320a (miR-320a) and Sirtuin 4 (SIRT4) was investigated in POI mouse ovaries oocytes and human granulosa cells (hGCs) by fluorescence-activated cell sorting (FACS), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence experiments. hAMSC-Exos improved proliferation, inhibited apoptosis, and decreased the expression of SIRT4 and relative genes in POI hGCs and ovaries. hAMSC-Exos elevated ovarian function and prohibited SIRT4 expression in oogenesis. The therapeutic effects were attenuated when miR-320a was knocked down. hAMSC-Exos decreased the ROS levels in POI hGCs and oocytes and improved ovarian weight and litter size, except for the Exosanti-miR-320a/POI group. Finally, hAMSC-Exos reduced the SIRT4 and ROS levels in POI ovaries and hGCs. The downstream protein expression (ANT2, AMP-dependent kinase [AMPK], and L-OPA1) was downregulated in the hGCs-SIRT4KD group but disappeared in the Exosanti-miR-320a/POI group. Our study is the first to illustrate the therapeutic potential of hAMSC-Exos in POI. Exosomal miR-320 plays a key role in the hAMSC-Exos-mediated effects on ovarian function via SIRT4 signaling.

Abstract Background Human amniotic epithelial cell (hAEC) transplantation holds great promise in treating premature ovarian insufficiency (POI). However, some deficient biological characteristics of hAECs restrict their application. Methods Vitamin C (VC) was added to the culture media of hAECs for 2 weeks. Then, the proliferative ability, migration ability, pluripotency, and self-renewal of VC-treated hAECs (VC-hAECs) were determined. Next, hAECs and VC-hAECs were transplanted into the ovaries of cyclophosphamide (CTX)-induced POI model mice. The ovarian function of POI mice was evaluated after transplantation by counting follicle numbers and measuring the blood levels of AMH, E2, and FSH. The rescue effects of VC-hAECs and hAECs were unveiled by coculturing with CTX-damaged human ovarian granulosa cells (hGCs) and analyzing relative marker expression. Additionally, ovarian marker expression and transplant survival were detected in POI mice after transplantation to verify the beneficial effect of VC-hAECs. The cytokine profiles of VC-hAECs and hAECs were revealed by performing a cytokine array and an ELISA to show their paracrine function. Results Our results indicated that VC promoted the proliferation, migration, pluripotency, and self-renewal of hAECs in vitro. The most effective concentration of VC was 50 μg/ml. After transplantation into the POI mouse model, VC-hAECs reversed ovarian function more powerfully than hAECs. Human granulosa cell marker expression in CTX-damaged hGCs was increased after coculture with VC-hAECs compared with hAECs. In the ovaries of the POI mice, ovarian marker expression was greater after VC-hAEC transplantation than after hAEC transplantation. VC-hAECs showed higher transplant survival than hAECs. Furthermore, VC-hAECs secreted more growth factors than hAECs. Conclusion Treatment with VC promoted the proliferation, migration, self-renewal, and paracrine functions of hAECs. Additionally, VC elevated the therapeutic potential of hAECs in treating POI.

Taxol is a widely used chemotherapy drug used clinically for ovarian cancer, although the response to Taxol among individuals varies due to the heterogeneity among ovarian cancer patients. In this work, we analyzed differences in the prognostic effect of gene expression and Taxol usage in the Cancer Genome Atlas (TCGA) dataset and identified specific genes associated with the Taxol effect. Using the Cox regression model, a risk model (Taxol score) was developed to assess the outcome of ovarian cancer patients who underwent chemotherapy with Taxol. According to the results, survival was significantly associated with the Taxol score. Moreover, the patients in the high and low Taxol score group had different responses to Taxol. This result was further validated in another two independent datasets. The correlation between clinicopathological indicators was also analyzed, and we determined that the Taxol score is not associated with age, pathological stage, or Taxol treatment, while there was significant correlation with tumor size and grade. Gene Set Enrichment Analysis (GSEA) showed that various signaling pathways including ECM receptor, drug metabolism and ascorbate metabolism pathways were significantly enriched in the high Taxol score group. Collectively, these results indicate that the model is robust for predicting the effectiveness of Taxol by reflecting the various cell statuses of serous ovarian carcinoma.

The long noncoding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to play a crucial role in cancer progression. However, the functions of SNHG20 in epithelial ovarian cancer (EOC) are not well established. The aim of the present study was to investigate SNHG20 clinical significance and its underlying mechanism in proliferation and metastasis in EOC. The expression level of SNHG20 was identified via in situ hybridization (ISH) and quantitative RT-PCR (qRT-PCR). The proliferative and metastatic capacities by silencing SNHG20 expression in A2780 and CAOV-3 cells were measured by cell counting kit-8 (CCK-8) and transwell assays. The molecular mRNA and protein expressions were examined using qRT-PCR, Western blot, and double immunofluorescent staining. SNHG20 expression was markedly higher in serous EOC tissues than that in adjacent tissues and closely correlated with histological grade and lymph node (LN) status. Patients with high SNHG20 showed a shorter overall survival (OS) and SNHG20 was an independent risk factor for the prognosis of serous EOC. Knockdown of SNHG20 remarkably inhibited EOC cell proliferation, migration, and invasion, which was associated with dysregulation of P21, Cyclin D1, E-cadherin, and Vimentin. These results suggest that SNHG20 may serve as an independent prognostic predictor and function as a noncoding oncogene in EOC progression, which might be a possible novel diagnostic marker and treatment target. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the preliminary mechanism of action of B7 homolog 1 (B7.H1) and investigate the association between B7.H1 and cervical cancer. The expression of B7 family proteins was measured in cervical cancer cells. Cervical cancer cells were co.cultured with T lymphocytes. An ELISA assay was subsequently conducted to analyze cytokine concentrations in the supernatants of the cultured T cells in cervical cancer cells and B7.H1 downregulated cells. Levels of interleukin (IL).1ƒÀ, IL.6 and tumor necrosis factor.ƒ¿ mRNA in mice injected with cervical cancer cells or B7.H1 downregulated cells were measured by reverse transcription.quantitative polymerase chain reaction. It was determined that cervical cancer cells express high levels of B7.H1, whereas the normal cervical epithelium does not express B7.H1. When co.cultured with T lymphocytes, cervical cancer cells were involved in the inhibition of lymphocyte activation. When B7.H1 was downregulated using a lentivirus, the proliferation ability did not change compared with cervical cancer cells, whereas the soluble factors secreted by T cells differed between cervical cancer cells and B7.H1 downregulated cells. In an animal model, injected B7.H1 downregulated cervical cancer cells elicited a more intense immune response, whereas cervical cancer cells had the wild immune response. Therefore, the results of the present study demonstrate that B7.H1 mediates the low immunogenicity of cervical cancer and is not attacked by the immune system. [ABSTRACT FROM AUTHOR]