The role of GADD45G methylation in endometrial cancer: Insights into CDK1/CCNB1 activation and therapeutic opportunities.

INTRODUCTION: Accumulating evidence suggests the significant involvement of GADD45G in the development of various cancers. This study investigates GADD45G's involvement and methylation status in endometrial cancer (EC), along with molecular mechanisms and potential therapies. METHODS: The expression of GADD45G in EC tissues and controls was evaluated using RNA-seq, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting (WB). Methylation-specific PCR (MSP) evaluated GADD45G's methylation status. Protein-protein interaction (PPI) prediction identified potential interactors of GADD45G, and co-immunoprecipitation (co-IP) confirmed GADD45G interact with Cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). Several cell behavior assays were conducted in both in vitro and in vivo settings to comprehensively understand the impact of GADD45G dysregulation in EC. RESULTS: Our findings revealed a significant decrease in the expression of GADD45G in endometrial cancer tissues and cells, which was attributed to its methylation status. Reduced GADD45G expression correlated with increased invasive behaviors in EC cells. Furthermore, GADD45G negatively regulated CDK1 and CCNB1, promoting invasive behaviors at transcript and protein levels. CONCLUSION: This study demonstrated that the downregulation of GADD45G, mediated by methylation, facilitates the invasive behaviors of EC cells through interaction with the CDK1/CCNB1. These findings enhance understanding of the molecular mechanisms underlying endometrial cancer and suggest potential therapeutic strategies targeting GADD45G for treatment.

Knowledge, attitudes, and practices among Chinese reproductive-age women toward uterine adenomyosis.

Objective: This study aimed to assess the knowledge, attitudes and practices (KAP) among Chinese reproductive-age women toward uterine adenomyosis. Methods: This web-based cross-sectional study was conducted between April 2023 and September 2023 at the Second Hospital of Hebei Medical University. A self-designed questionnaire was developed to collect demographic information of reproductive-age women, and assess their KAP toward uterine adenomyosis. Results: A total of 520 valid questionnaires were collected. Among the participants, 127 (24.42%) were diagnosed with uterine adenomyosis, and 120 (23.08%) were accompanied by uterine fibroids. The mean knowledge, attitudes and practices scores were 3.54 ± 3.72 (possible range:0-10), 20.96 ± 3.19 (possible range:5-25) and 24.01 ± 4.95 (possible range:7-35), respectively. The structural equation model demonstrated that knowledge had direct effects on attitudes and practices, as indicated by a path coefficient of 0.714 (p < 0.001) and 1.510 (p < 0.001), respectively. Moreover, attitudes had direct effects on practices, with a path coefficient of 0.226 (p = 0.001). Conclusion: The findings revealed that reproductive-age women have insufficient knowledge, negative attitudes, and poor practices toward the uterine adenomyosis. Comprehensive training programs are needed to improve reproductive-age women practices in this area.

ENST00000534735 inhibits proliferation and migration, promotes apoptosis and pyroptosis of endometrial cancer via OSBPL3 through APMK/SIRT1/NF-κB pathway.

Background: The complete understanding of the biological roles of long non-coding RNAs (lncRNAs) in cancer remains elusive. The findings of this study indicate that the newly discovered lncRNA ENST00000534735 exhibited a decreased expression in both endometrial cancer (EC) tissues and cell lines. Methods: The expression of ENST00000534735 in EC tissues was detected using RNA-sequencing analysis. The effects of ENST00000534735 on cell proliferation, migration, apoptosis, and pyroptosis were determined via in vitro and in vivo experiments. The proteins that interact with ENST00000534735 were confirmed by RNA pull-down assay. Furthermore, an investigation was conducted on the impact of ENST00000534735 on the in vivo growth of EC through a tumorigenicity assay in nude mice. Results: We found that ENST00000534735 was significantly down-regulated in EC tissues compared to their adjacent non-cancerous tissues. The ectopic expression of ENST00000534735 drastically inhibited lung cancer cell proliferation and migration ability and facilitated apoptosis and pyroptosis. Knockdown of ENST00000534735 increased OSBPL3 expression, and the tumor-suppressing effects of ENST00000534735 overexpression were reversed by upregulation of OSBPL3 via the APMK/SIRT1/NF-κB pathway. The in vivo tumorigenic assays conducted on nude mice revealed that the excessive expression of ENST00000534735 impeded the growth of EC. Conclusions: All results elucidated the role and molecular mechanism of ENST00000534735 in the malignant development of EC. ENST00000534735, a new antioncogene in EC, may serve as a survival biomarker or therapeutic target for EC.

Dilatation and curettage versus lesion resection in the treatment of cesarean-scar-pregnancy: A systematic review and meta-analysis.

This meta-analysis was performed to compare the efficacy and safety of dilatation and curettage (D&C) (simply D&C or combined with other treatments) and lesion resection for cesarean scar pregnancy (CSP). A search of English and Chinese databases from 2010 to 2019 was conducted. Thirty one studies were retrieved including sixteen random controlled and fifteen case controlled trials. Compared with abdominal resection surgery(ARS) and vaginal resection surgery(VRS), uterine artery embolization(UAE)+D&C has no obvious difference in curative effect and safety (UAE + D&C versus ARS: Cure rate(CR): P = 0.076, time for menstruation recovery/ß-HCG normalization: P = 0.545/0.949,Blood loss: P = 0.005, adverse event: P = 0.420; versus VRS: CR: P = 0.085, time for menstruation recovery/ß-HCG normalization: P < 0.001/P = 0.031,Blood loss: P = 0.902, adverse event: P = 0.249). UAE + D&C associated with lower blood loss and less postoperative complication than laparoscopic resection surgery(LRS), but LRS take more advantages in terms of the curative effect (CR: P = 0.047, time for menstruation recovery/ß-HCG normalization: P = 0.352/0.103). The efficacy and safety of VRS are better than D&C, methotrexate (MTX) + D&C (D&C versus VRS: CR: P < 0.001, time for ß-HCG normalization: P = 0.363,blood loss: P < 0.001, adverse event: P = 0.046; MTX + D&C versus VRS: CR: P < 0.001, time for menstruation recovery/ß-HCG normalization: P < 0.001/P = 0.005, blood loss: P < 0.001, adverse event: P < 0.001). Lesion resection had advantages in shorter time for menstrual recovery/ß-HCG normalization and less adverse events, lower failure rate over the administration of D&C treatments. In detail, the curative effect of UAE + D&C is similar to ARS and VRS, but inferior to LRS, while the safety of UAE + D&C is better than LRS. The efficacy and safety of simply D&C and MTX + D&C are not as good as VRS.

Clinical efficacy of adenomyomectomy using "H" type incision combined with Mirena in the treatment of adenomyosis.

To evaluate the clinical efficacy and safety of adenomyomectomy using "H" type incision combined with Mirena (LNG-IUS) in the treatment of adenomyosis.A total of 57 women with adenomyosis who underwent adenomyomectomy using "H" type incision combined with LNG-IUS were selected. Visual analog scale (VAS), menstrual flow, uterine volume, serum CA125 levels and hemoglobin amounts were compared before and after the surgery. Meanwhile, postoperative pregnancy, adverse reactions, and recurrence were observed.VAS score, menstrual flow, uterine volume, and serum CA125 levels in 53 patients were significantly reduced after surgery (P < . 001). Moreover, statistical significances were obtained for VAS score at 13 and 6 months, menstrual flow at 1, 3, 6, 12, and 24 months, uterine volume at 1, 3, 6, 12, 24, and 36 months and CA125 levels at 1 and 3 months (P < .05). Of the 5 patients with fertility requirements, 1 became pregnant after IVF-ET, progressed to preterm, and delivered healthy twins. Among all related adverse reactions, amenorrhea was the most common (n = 20, 37.7%). There were no cases of LNG-IUS removal, ectopia, expulsion, and incarceration, except in 2 patients due to pregnancy, 1 due to uterine bleeding, and 1 due to Mirena perforation from incision of the uterine fundus. All patients showed no relapse.Adenomyomectomy using "H" type incision combined with Mirena constitutes a novel and effective conservative surgical procedure for adenomyosis treatment.