FZD3 regulates the viability, apoptosis, and extracellular matrix degradation of vaginal wall fibroblasts in pelvic organ prolapse via the Wnt signaling pathway.

The occurrence of pelvic organ prolapse (POP) seriously affects women's quality of life. However, the pathogenesis of POP remains unclear. We aimed to clarify the role of Frizzled class receptor 3 (FZD3) in POP. FZD3 expression in the vaginal wall tissues was detected using immunohistochemistry, real-time polymerase chain reaction, and western blot analysis. Then, vaginal wall fibroblasts (VWFs) were isolated from patients with POP and non-POP, and were identified. Cell viability and apoptosis were evaluated using Cell Counting Kit-8 and flow cytometry, respectively. Extracellular matrix (ECM) degradation was assessed by western blot analysis. The results illustrated that FZD3 was downregulated in POP. VWFs from POP had lower cell viability, ECM degradation, and higher apoptosis. Knockdown of FZD3 inhibited cell viability, ECM degradation, and promoted apoptosis of VWFs, whereas overexpression of FZD3 had opposite results. Moreover, IWP-4 (Wingless-type [Wnt] pathway inhibitor) reversed the role of FZD3 overexpression on biological behaviors. Taken together, FZD3 facilitates VWFs viability, ECM degradation, and inhibits apoptosis via the Wnt pathway in POP. The findings provide a potential target for the treatment of POP.

Effects of different treatment methods on clinical efficacy and fertility outcomes of patients with adenomyosis.

OBJECTIVE: This trial was to investigate the effect of different treatment methods on the clinical efficacy and fertility outcome of patients with adenomyosis. METHODS: In total, 140 patients with adenomyosis were evenly and randomly allocated into group A (laparoscopic surgery), group B (laparoscopic surgery combined with gonadotropin-releasing hormone analogs [GnRH-a]), group C (ultrasound-guided percutaneous radiofrequency ablation), and group D (ultrasound-guided percutaneous radiofrequency ablation combined with GnRH-a). On the 3rd day after surgery, patients in group B and group D were subcutaneously injected with GnRH-a (Leuprorelin Acetate SR for Injection) at 3.75 mg/time, once every 4 weeks, for a total of 3 months. The therapeutic effects of the 4 groups were compared, including menstrual volume, dysmenorrhea score, uterine volume, clinical efficacy, luteinizing hormone (LH), estradiol (E2), and follicle-stimulating hormone (FSH) levels, CA125 levels, recurrence, pregnancy status, and pregnancy outcomes. RESULTS: After treatment, the menstrual volume of 4 groups was lowered, dysmenorrhea, Visual Analog Scale (VAS) score, LH, FSH, E2, and CA125 levels were reduced, and uterine volume was decreased. The menstrual volume, VAS score, levels of LH, FSH, E2, and CA125, and uterine volume were reduced in groups B, C, and D compared with group A, and the decrease was more significant in group D. The total effective rate of group D was 100.00%, which was higher than that of group A (71.43%), group B (80.00%), and group C (82.86%). After one year of drug withdrawal, the recurrence of hypermenorrhea, dysmenorrhea, uterine enlargement, and excessive CA125 in group D was significantly lower than that in groups A, B and C, and the recurrence in groups B and C was significantly lower than that in group A (P < 0.05). Compared with groups A, B, and C, group D had a higher pregnancy rate, natural pregnancy rate, and lower in vitro fertilization-embryo transfer rate (P < 0.05), but showed no significant difference in pregnancy outcomes. CONCLUSION: Ultrasound-guided percutaneous radiofrequency ablation combined with Leuprorelin Acetate is effective in the treatment of adenomyosis, which can effectively relieve clinical symptoms, protect postoperative ovarian function, reduce recurrence rate, alleviate pain, and improve quality of life.

Identification of N1 methyladenosine-related biomarker predicting overall survival outcomes and experimental verification in ovarian cancer.

AIM: This study aimed to construct a N1-methyladenosine (m1A)-related biomarker model for predicting the prognosis of ovarian cancer (OVCA). METHODS: OVCA samples were clustered into two subtypes using the Non-Negative Matrix Factorization (NMF) algorithm, including TCGA (n = 374) as the training set and GSE26712 (n = 185) as the external validation set. Hub genes, which were screened to construct a risk model, and nomogram to predict the overall survival of OVCA were explored and validated through various bioinformatic analysis and quantitative real-time PCR. RESULTS: Following bootstrap correction, the C-index of nomogram was 0.62515, showing reliable performance. The functions of DEGs in the high- and low-risk groups were mainly enriched in immune response, immune regulation, and immune-related diseases. The immune cells relevant to the expression of hub genes were explored, for example, Natural Killer (NK) cells, T cells, activated dendritic cells (aDC). CONCLUSIONS: AADAC, CD38, CACNA1C, and ATP1A3 might be used as m1A-related biomarkers for OVCA, and the nomogram labeled with m1A for the first time had excellent performance for predicting overall survival in OVCA.

Effects of the SPI/lncRNA NEAT1 Axis on Functions of Trophoblast and Decidual Cells in Patients with Recurrent Miscarriage.

Recurrent miscarriage (RM) is a frustrating and complex pregnancy disorder and long noncoding RNAs (lncRNAs) modulate susceptibility to RM. This study expounded on the role of specificity protein 1 (SP1) in functions of chorionic trophoblast and decidual cells via regulating lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1). Chorionic villus tissues and decidual tissues of RM patients and normal pregnant women were collected. Real-time quantitative polymerase chain reaction and Western blotting revealed that SP1 and NEAT1 were downregulated in trophoblast and decidual tissues of RM patients, and the Pearson correlation analysis detected that they were positively correlated in expression level. Chorionic trophoblast and decidual cells of RM patients were isolated and intervened by vectors over-expressing SP1 or NEAT1 siRNAs. Thereafter, the cell counting kit-8, Transwell, flow cytometry assays detected that SP1 overexpression accelerated trophoblast cell proliferation, invasion, and migration, meanwhile, enhancing decidual cell proliferation while repressed apoptosis. Next, the dual-luciferase and Chromatin immunoprecipitation assays showed that SP1 bound to the NEAT1 promoter region and further activated NEAT1 transcription. Silencing NEAT1 reversed the efforts of SP1 overexpression on the functions of trophoblast and decidual cells. Overall, SP1 activated NEAT1 transcription, accelerating trophoblast cell proliferation, invasion, and migration and mitigating decidual cell apoptosis.

The effects of mifepristone on the structure of human decidua and chorion and Bax and Bcl-2 expression at early stage of pregnancy.

BACKGROUND: As a progesterone receptor antagonist, mifepristone combined with misoprostol is widely used to terminate early pregnancy in clinical practice. It has also been reported that mifepristone may cause cell death in decidual cells and result in hemorrhage of the decidua and insufficient blood supply. However, little is known about the histological effects of mifepristone on human decidua and chorion. METHODS: Histological and subcellular structural changes of decidua and chorionic villi from women taking mifepristone at early pregnancy times were examined by Hematoxylin and eosin (H&E) staining and transmission Electron microscope. The expression of apoptosis-related proteins Bax/Bcl-2 was examined by immunohistochemistry. RESULTS: After 48 h of mifepristone administration, the decidua tissue and chorionic villus structures were altered in women within 39-49 days of gestation and displayed varying degrees of degeneration and necrosis-like features. Apoptotic events were observed in the decidua and chorionic villi of early pregnancy, and mifepristone treatment significantly increases the number of apoptotic cells. The increased apoptotic events were concomitant with the increased expression of Bax and decreased expression of Bcl-2. CONCLUSION: This study provides evidence that mifepristone induces histological and subcellular changes in decidua and chorionic villi. Mifepristone modulates the relative ratio of Bax/Bcl-2 and the increased apoptosis contributes to the pregnancy termination at early stage of pregnancy.

Estrogen Exerts Neuroprotective Effects in Vascular Dementia Rats by Suppressing Autophagy and Activating the Wnt/ß-Catenin Signaling Pathway.

Vascular dementia (VD) is a clinical syndrome of acquired cognitive dysfunction caused by various cerebrovascular factors. Estrogen is a steroid hormone involved in promoting neuronal survival and in regulating many signaling pathways. However, the mechanism by which it confers neuroprotective effects in VD remains unclear. Here, we aimed to investigate the effect of estrogen on neuronal injury and cognitive impairment in VD rats. Adult female rats were randomly divided into four groups (sham, model, estrogen early and estrogen later treatment) and received sham surgery or bilateral ovariectomy and permanent occlusion of bilateral common carotid arteries (BCCAO). The early treatment group received daily intraperitoneal injections of 17ß-estradiol (100 µg/kg/day) for 8 weeks starting the day after BCCAO. The later treatment group was administered the same starting 1 week after BCCAO. Learning and memory functions were assessed using the Morris water maze. Morphological changes within the hippocampal CA1 region were observed by hematoxylin/eosin staining and electron microscopy. Expression of proteins associated with autophagy and signaling were detected by immunohistochemical staining and Western blot. We found that estrogen significantly alleviated cognitive damage and neuronal injury and reduced the expression of Beclin1 and LC3B, indicating a suppression of autophagy. Moreover, estrogen enhanced expression of ß-catenin and Cyclin D1, while reducing glycogen synthase kinase 3ß, suggesting activation of Wnt/ß-catenin signaling. These results indicate that estrogen ameliorates learning and memory deficiencies in VD rats, and that this neuroprotective effect may be explained by the suppression of autophagy and activation of Wnt/ß-catenin signaling.

Suppression of miR-93-5p inhibits high-risk HPV-positive cervical cancer progression via targeting of BTG3.

This study explores the role of miR-93-5p in high-risk HPV-positive (HR-HPV) cervical cancer by targeting of BTG3. Cervical tissues were collected from 332 patients with conditions of chronic cervicitis (n = 42), low-grade cervical intraepithelial neoplasia (CIN I, n = 51), CIN II (n = 49), CIN III (n = 43), cervical cancer (n = 90), and normal cervical tissues (n = 57). HR-HPV DNA was detected by Hybrid Capture 2, and the expressions of miR-93-5p and BTG3 were determined by qRT-PCR and Western blot. The target relationship between miR-93-5p and BTG3 was verified by dual-luciferase reporter gene assay. HPV-positive cervical cancer cells (CaSki and HeLa) were divided into control, NC, inhibitor, BTG3, and mimic + BTG3 groups. CCK-8, Annexin V-APC/PI, and Transwell assays were applied to evaluate cell biological activities. MiR-93-5p was positively related but BTG3 was inversely related to HR-HPV infection. Additionally, miR-93-5p expression was negatively correlated with BTG3 expression in cervical cancer tissues infected with HR-HPV. HPV-positive cervical cancer cells showed higher miR-93-5p and lower BTG3 levels than negative cells. CaSki and HeLa cells in the inhibitor group showed increased BTG3 compared with the control group. After transfection with miR-93-5p inhibitor or BTG3 activation plasmid, proliferation and metastasis were inhibited, but apoptosis was promoted. The mimic + BTG3 group showed increased cell proliferation and metastasis but decreased cell apoptosis compared with the BTG3 group. Upregulated miR-93-5p was positively related but downregulated BTG3 was inversely related to HR-HPV infection, and inhibition of miR-93-5p may have blocked HPV-positive cervical cancer development by targeting of BTG3.

Primary squamous cell carcinoma of the endometrium in a woman of reproductive age: a rare case report.

Primary endometrial squamous cell carcinoma is an extremely rare tumor that tends to occur in postmenopausal women. We report on a 33-year-old woman who presented with a history of irregular vaginal bleeding for more than 2 years, and a vaginal mass for more than 1 month. Biopsy of the vaginal mass revealed an invasive poorly differentiated squamous cell carcinoma. The patient underwent radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic lymph node dissection, peritoneal sampling and vaginal tumor resection. On the basis of her medical history, auxiliary examination and postoperative pathology, the patient was diagnosed with stage IV endometrial squamous cell carcinoma. The patient was followed-up regularly and remained in good condition.

MicroRNA-519a inhibits the proliferation and promotes the apoptosis of ovarian cancer cells through targeting signal transducer and activator of transcription 3.

Ovarian cancer is a highly prevalent cancer among women. Recent studies have indicated that microRNAs (miRs) may serve important roles in the pathogenesis of ovarian cancer. miR-519a was observed to be downregulated in tissue samples of patients with ovarian cancer; however, its role in ovarian cancer requires further investigation. The aim of the present study was to examine the role of miR-519a in the pathogenesis of ovarian cancer and determine its direct target. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to examine the expression of miR-519a in 20 patients ovarian cancer and 20 normal ovarian tissue samples. Subsequently, SKOV3 cells were cultured and transfected with miR-519a mimics, while MTT and Annexin V assays were performed to investigate the role of miR-519a in the proliferation and apoptosis of SKOV3 cells. In addition, RT-qPCR and western blotting were used to determine the expression levels of miR-519a, signal transducer and activator of transcription 3 (STAT3), myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) in untransfected and miR-519a mimic-transfected SKOV3 cells. Dual-luciferase reporter assay was also performed to confirm whether STAT3 was a direct target of miR-519a. The results revealed that miR-519a was significantly downregulated in tissue samples of patients with ovarian cancer as compared with the normal ovarian tissues. Furthermore, transient overexpression of miR-519a inhibited the proliferation and promoted the apoptosis of SKOV3 cells, as well as decreased the mRNA and protein expression levels of STAT3, Mcl-1 and Bcl-xl. Finally, dual-luciferase reporter assay confirmed that STAT3 was a direct target of miR-519a. In conclusion, the present study proved for the first time that miR-519a functions as a tumor suppressor by targeting STAT3 in ovarian cancer, suggesting that miR-519a may be a potential biomarker for the diagnosis and treatment of ovarian cancer.

Long noncoding RNA colon cancer associated transcript­1 promotes the proliferation, migration and invasion of cervical cancer.

Previous studies have revealed significant roles for long noncoding RNA (lncRNA) in the tumorigenesis, metastasis and invasion of various tumors, including cervical cancer. The present study aimed to investigate the potential roles of lncRNA colon cancer associated transcript 1 (CCAT1) in the metastasis and invasion of cervical cancer, and to reveal the potential underlying mechanism. The mRNA expression of lncRNA CCAT1 in cervical cancer tissue was measured using the reverse transcription­quantitative polymerase chain reaction, and the association between lncRNA CCAT1 and the metastasis of cervical cancer was analyzed. The effects of lncRNA CCAT1 expression on HeLa cell viability, and migration and invasion were also analyzed by MTT and Transwell assays. The results demonstrated that lncRNA CCAT1 was highly expressed in the cervical cancer tissue compared with the adjacent normal tissue. High expression of lncRNA CCAT1 was positively associated with tumor size, and there was correlation between high lncRNA CCAT1 expression and a poor survival rate of cervical cancer. The cell viability, and migratory and invasive abilities were suppressed by silencing CCAT1. The results of the present study indicate that lncRNA CCAT1 was highly expressed in cervical cancer, and may serve important roles in promoting the progression and metastasis of cervical cancer.