Ovarian cancer is the most lethal gynaecological cancer and the sixth most common cause of cancer related death among Western women. Recent studies show that harmine, a small-molecular β-carboline alkaloid present in medicinal plants, displayed obvious anticancer effects in several cancer cells. However, the effect of harmine on ovarian cancer is not well understood. In the present study, the effect of harmine on the cell proliferation and migration of ovarian cancer SKOV-3 cells and the underlying mechanism were investigated. Our results indicated that harmine significantly suppressed the proliferation of SKOV-3 cells in a dose-dependent manner. Interestingly, it also inhibited the epidermal growth factor (EGF)-induced proliferation of SKOV-3 cells. Moreover, the migration of SKOV-3 cells was markedly inhibited by harmine treatment. Further study showed that harmine inhibited not only the basal phosphorylation level of extra-cellular signal-regulated kinase 1/2 (ERK1/2) and cyclic adenosine monophosphate response element-binding protein (CREB) but also EGF-induced ERK1/2 and CREB phosphorylation. Finally, harmine significantly suppressed the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) family MMP-2, and MMP-9. In conclusion, our data revealed that harmine inhibited the proliferation and migration of SKOV-3 cells, which might be mediated by ERK/CREB pathway. These findings elucidate that harmine may act as a potential therapeutic drug for ovarian cancer treatment.

Background: Menopausal and postmenopausal women often experience vaginal atrophy due to estrogen deficiency. Mesenchymal stem cell exosomes have emerged as potential therapeutic agents, capable of promoting tissue regeneration and repair. Objective: This study aimed to explore the benefits of exosomes on VK2 cells and the therapeutic effect of topical exosomal hydrogel on atrophic vaginas. Methods: Exosomes were extracted using the high-speed centrifugation method, and their effects on VK2 cell proliferation, migration, and differentiation were observed through co-culture. The menopause model was induced by ovariectomy in rats, followed by the injection of exosome-loaded hydrogel into their vaginas. The treatment's effectiveness was evaluated by measuring vaginal epithelium thickness using HE staining, and assessing vaginal mucosa proliferation and lamina propria angiogenesis using Ki67 and anti-CD31 staining, respectively. Results: Exosomes significantly promoted VK2 cell proliferation and migration, but had no significant effect on differentiation. The exosome hydrogel increased the expression of Ki67 and CD31, leading to a significant improvement in epithelial thickness. Conclusions: UcMSC- ex can stimulate the proliferation and migration of VK2 cells, but do not appear to promote differentiation. Topical application of exosome hydrogel enhances vaginal epithelium thickness to a certain degree, offering a promising non-hormonal therapeutic strategy to alleviate vaginal atrophy in postmenopausal women.

Atrophic vaginitis is very common in postmenopausal women due to declining estrogen levels. Vitamin D plays an important role in promoting epithelial cell proliferation, migration and adhesion. We established a rat model of ovariectomy (OVX) induced atrophic vaginitis with the aim of investigating the effects of Vitamin D supplementation on the vaginal epithelial barrier. The results showed that ovariectomised rats had significantly higher vaginal pH, reduced Lactobacillus, significantly lower uterine and vaginal weights, and lower vaginal epithelial PCNA, occludin, and E-cadherin mRNA expression compared with sham-operated rats. Vitamin D supplementation could reduce the vaginal pH, promote the proliferation and keratinization of vaginal epithelial cells, enhance the expression of PCNA mRNA in vaginal tissues, and improve the vaginal and uterine atrophy. Vitamin D can also increase the expression of E-cadherin and occludin proteins in vaginal tissues, maintain the integrity of the vaginal epithelium, increase the number of Lactobacillus, and reduce pathogenic bacterial infections. In vitro experiments demonstrated that 1,25(OH)₂D₃ could promote the proliferation and migration of VK2/E6E7 vaginal epithelial cells and increase the expression of E-cadherin protein. In conclusion, we demonstrated that Vitamin D can regulate the expression of vaginal epithelial tight junction proteins, promotes cell proliferation, and improves vaginal atrophy due to estrogen deficiency.

Introduction: Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or even contradictory views.Objectives: The present meta-analysis aimed to evaluate the effectiveness and safety of Metformin with or without CC and to compare them with LOD with or without CC (Met/Met-CC vs. LOD/LOD-CC) in women with CCR-PCOS who also have anovulation.Data source: The PubMed, Cochrane, and Embase databases were searched to identify relevant studies reported between 1 Jan 1966 and 31 Aug 2019; the search was updated on 17 May 2022.Study eligibility criteria: We included randomized controlled trials (RCTs) of CCR-PCOS that had considered Met/Met-CC and LOD/LOD-CC as the exposure variables and fertility as the main outcome variable.Study appraisal and synthesis methods: We assessed study quality using the Cochrane risk-of-bias tool. The primary effectiveness outcome was live birth/ongoing pregnancy rate and the primary safety outcome was miscarriage rate. A fixed-effect meta-analysis was performed. The robustness of the results was assessed using sensitivity analyses. Meta-regression and subgroup analysis were performed to examine the reasons for heterogeneity. Publication bias was examined using the funnel plot, Egger linear regression, and Begg rank correlation tests. The quality of this meta-analysis was estimated according to the GRADE approach. This meta-analysis has been registered in PROSPERO (CRD42021240156).Results: Among 71 potentially relevant studies, we included five RCTs in our meta-analysis. We found no difference in effectiveness between Met-CC and LOD in terms of live birth/ongoing pregnancy (RR = 1.02, 95% CI: 0.87–1.21, z = 0.28; p = 0.780), and miscarriage rates (RR = 0.79, 95% CI: 0.46–1.36, z = 0.86; p = 0.390). I2 tests results revealed moderate or no heterogeneity (I2 = 51.4%, p = 0.083; I2= 0.0%; p = 0.952). Sensitivity analysis confirmed the robustness of the results. Funnel plot, Egger linear regression, and Begg rank correlation tests implied no publication bias (p > 0.05). LOD was more expensive than Met (€1050 vs. €50.16). The evidence quality was moderate.Conclusion: There is no evidence on the difference in the outcomes between the two interventions regarding ovulation, pregnancy, and live birth. As LOD is an invasive procedure and carries inherent risks, the use of Met/Met-CC should be the second-line treatment for women with CCR-PCOS.Systematic Review Registration: identifier CRD42021240156.

Human papillomavirus (HPV) infection, cervical intraepithelial neoplasia (CIN), pelvic organ prolapse (POP), cervical polyps, abnormal uterine bleeding, and vaginitis are common gynecological disorders. This study characterized the vaginal microbiome and its cytokine-mediated immune interactions in Chinese women with gynecological disorders. Vaginal swabs from 310 patients diagnosed with gynecological disorders and 112 healthy controls were analyzed via 16S rRNA gene sequencing and cytometric bead array (CBA) to evaluate proinflammatory cytokines. Findings on correlation were validated through in vitro co-culture experiments. HPV infection and CIN were associated with dysbiotic microbial profiles and elevated levels of IL-1α, IL-1β, IL-6, IL-8, MCP-1, and MIG. Stratification by microbial composition demonstrated that HPV/CIN patients with non- Lactobacillus -dominant microbiomes harbored the highest IL-1α and IL-1β concentrations. Validated through computational modeling and in vitro analyses, Lactobacillus crispatus and Lactobacillus iners were identified as being strongly inversely correlated with IL-1α and IL-1β expression. Conversely, non- Lactobacillus taxa, including Bifidobacterium breve , Prevotella bivia , Gardnerella vaginalis, Sneathia amnii, Sneathia sanguinegens, Prevotella amnii, Escherichia coli , and Chlamydia trachomatis , exhibited positive correlations with proinflammatory cytokines. These findings highlight a connection between Lactobacillus species and reduced inflammation, while non- Lactobacillus dominance is linked to increased cytokine-driven responses. This study provides valuable insights into microbiome-immune crosstalk in gynecological diseases.

Human papillomavirus (HPV) infection, cervical intraepithelial neoplasia (CIN), pelvic organ prolapse (POP), cervical polyps (CP), abnormal uterine bleeding (AUB), and vaginitis are common conditions encountered in gynecological practice. In this study, we collected vaginal secretions from patients diagnosed with these diseases (n = 310) and from healthy donors (n = 112) to analyze their vaginal microbiome using 16S rRNA sequencing and cytokine expression using a cytometric bead array (CBA). Our findings revealed that the vaginal microbiome in POP patients exhibited higher complexity compared to other groups. Regarding cytokine expression, levels of IL-1α, IL-1β, IL-6, IL-8, MCP-1, and MIG were significantly elevated in HPV and CIN patients. Analysis of microbial associations showed that Lactobacillus crispatus and Lactobacillus iners were significantly negatively correlated with IL-1α and IL-1β expression. In contrast, non- Lactobacillus bacteria, including Bifidobacterium breve, Prevotella bivia, Gardnerella vaginalis, Sneathia amnii, Sneathia sanguinegens, Prevotella amnii, Escherichia coli, and Chlamydia trachomatis , were positively correlated with IL-1α, IL-1β, IL-6, IL-8, MCP-1, and MIG levels. Furthermore, Lactobacillus iners exhibited a significant negative effect in the HPV and CIN patient groups.