Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression.

BACKGROUND: Gallic acid (GA) is an organic compound with phenolic properties that occurs naturally and can be found in Guizhi Fuling capsules, showcasing a wide range of biological functionalities. PURPOSE: The objective of this study was to examine the influence of GA on endometrial hyperplasia (EH) and elucidate its underlying mechanism. METHODS: Initially, the induction of EH was achieved by administering estradiol to mice via continuous subcutaneous injection for a duration of 21 days. Concurrently, GA treatment was administered, and subsequently, the uterine tissue structure was assessed using hematoxylin and eosin (H&E) staining. Following this, the proliferation of human endometrial cells treated by GA was determined utilizing the CCK-8 method. Furthermore, network pharmacology and single-cell-RNA-seq data were employed to identify the target of GA action. In addition, we will employ immunofluorescence (IF), immunohistochemistry (IHC), flow cytometry, western blot and RT-qPCR methodologies to investigate the impact of GA on the expression level of cyclin D1, PI3K, p-PI3K, AKT, p-AKT. RESULTS: GA treatment ameliorated histopathological alterations in the uterus and suppress proliferation. Estradiol stimulation can activate the PI3K/AKT pathway, leading to up-regulation of cyclin D1 expression, whereas GA treatment results in down-regulation of its expression. CONCLUSIONS: The expression of cyclin D1 is down-regulated by GA through the inhibition of the PI3K/AKT pathway, effectively mitigating estradiol-induced EH in mice.

Bazedoxifene plus conjugated estrogens improve menopausal symptoms in postmenopausal women: a systematic review and meta-analysis.

Our aim is to evaluate the efficacy of bazedoxifene (BZA) plus conjugated estrogens (CE) on menopausal symptoms in postmenopausal women. A series of databases including PubMed, EMBASE, Medline, Web of science, China national knowledge internet and Wanfang database up to 31 October 2021 were searched, and randomized controlled trials (RCTs) of BZA/CE for menopausal symptoms were included. Seven RCTs involving 5431 patients were included in this study. Compared with placebo group, there were significantly reduce in daily number of hot flushes, daily number of moderate or severe hot flushes, the percentages of parabasal cells and the time to fall sleep when patients treated with BZA/CE. Besides, there were significant improvement in sleep disturbance and total MENQOL. However, no significant improvements in sleep adequacy were observed in the three groups. Furthermore, BZA 20 mg/CE 0.625 mg was more effective than BZA 20 mg/CE 0.45 mg in improving the menopausal symptoms. Therefore, both bazedoxifene 20 mg plus conjugated estrogens 0.45 mg and bazedoxifene 20 mg plus conjugated estrogens 0.625 mg could significantly improve the menopause-related symptoms and MENQOL in postmenopausal women, and the curative effects of BZA 20 mg/CE 0.625 mg were better than that of BZA 20 mg/CE 0.45 mg. These findings need to be further confirmed by more high-quality RCTs.

Analysis on clinical association of uterine scar diverticulum with subsequent infertility in patients underwent cesarean section.

ABSTRACT: To evaluate the relationship between uterine cesarean scar diverticulum (CSD) and subsequent infertility in patients who underwent cesarean section, and determine the effects of pelvic fluid-releasing inflammations on infertility.A retrospective analysis was designed among patients with CSD who were admitted to our hospital from January 1, 2018 to December 31, 2019. A total of 60 patients with CSD and uterine fibroids or benign ovarian tumors who underwent cesarean section were included, and divided into the CSD group and control group. Baseline characteristics of all patients were collected, and the pelvic adhesion scores and the percents of tubal patency were evaluated. Furthermore, the postoperative clinical outcomes were followed up. The levels of inflammatory factors in pelvic fluid were tested using Elisa kits.Preoperative data indicated that the size of the uterine scar diverticulum was (1.68 ±â€Š0.52) cm, the pelvic adhesion scores were higher in CSD group than control group (4.67 ±â€Š0.90 vs 0.47 ±â€Š0.90, P < .05), and 21 of 30 patients with unobstructed fallopian tubes. The levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in patients with CSD were obviously higher than control group (P < .05). After the follow-up, the data displayed that no CSD was found in all patients, the time of menstrual period in patients with CSD was shortened to 7.80 ±â€Š1.27 days, and the myometrial thickness at uterine scar was significantly increased (P < .05). Additionally, the pregnancy rate was increased, and 12 of 30 patients were repregnant. Correlation analysis showed that the levels of inflammatory factors (tumor necrosis factor-α, interleukin-1ß, interleukin-6), the size of uterine scar diverticulum, and the myometrial thickness at uterine scar were significantly correlated with subsequent infertility (r = 0.307, 0.083, 0.147, 0.405, 0.291, P < .05).Uterine scar diverticulum repair could improve menstrual prolongation, increased the thickness of myometrium and repregnant rate. Subsequent infertility was positively correlated with uterine scar diverticulum and the levels of inflammatory factors.