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Background: Limited studies have reported the relationship between intestinal flora dysbiosis and clinical characteristics in polycystic ovary syndrome (PCOS). However, the structure and characteristics of gut microbiota in PCOS have not been fully elucidated. Objective: To analyze the composition of the Intestinal flora population in normal-weight women with PCOS and insulin resistance(IR) compared to PCOS alone and healthy women. Methods: A total of 14 PCOS patients with insulin resistant(PCOS-IR) and 12 PCOS alone (PCOS-NIR), and 10 age- and body mass index-matched healthy control women (HC). BMI: 18.5–23.9 kg/m2. The bacterial 16 S rDNA V3-V4 fragment was amplified and sequenced. Then, the sequencing data were analyzed for species annotation, community diversity, and inter-group differences, to explore gut microbial characteristics of the subjects and their correlation with clinical parameters. Results: No significant difference in diversity was observed between PCOA and sample cluster analysis among the three groups (Beta-diversity) and Alpha-diversity. The relative abundance of Rothia, Ruminococcus, and Enterococcus was significantly higher in the PCOS-IR group than in the other two groups (P < 0.05), while that of Prevotella was dramatically decreased (P < 0.05). The abundance of Enterococcus was positively correlated with waist circumference, hip circumference, diastolic blood pressure, and insulin resistance index. Meanwhile, Rothia abundance is positively associated with waist circumference and free fatty acids. Conclusions: The gut microbial composition of PCOS patients with insulin resistance is different from that of PCOS alone and healthy women. The difference is correlated with the clinical characteristics of PCOS, with regards to insulin resistance, abdominal obesity, free fatty acids, and other indicators. PCOS-IR patients have an increased abundance of Enterococcus which potentially the intestinal environment of the host by enriching the metabolic pathways related to insulin resistance, causing the occurrence and development of PCOS. [ABSTRACT FROM AUTHOR]

Background: In contrast to stable genetic events, epigenetic changes are highly plastic and play crucial roles in tumor evolution and development. Epithelial ovarian cancer (EOC) is a highly heterogeneous disease that is generally associated with poor prognosis and treatment failure. Profiling epigenome-wide DNA methylation status is therefore essential to better characterize the impact of epigenetic alterations on the heterogeneity of EOC. Methods: An epigenome-wide association study was conducted to evaluate global DNA methylation in a retrospective cohort of 80 mixed subtypes of primary ovarian cancers and 30 patients with high-grade serous ovarian carcinoma (HGSOC). Three demethylating agents, azacytidine, decitabine, and thioguanine, were tested their anti-cancer and anti-chemoresistant effects on HGSOC cells. Results: Global DNA hypermethylation was significantly associated with high-grade tumors, platinum resistance, and poor prognosis. We determined that 9313 differentially methylated probes (DMPs) were enriched in their relative gene regions of 4938 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways. On the other hand, global DNA hypermethylation was preferentially associated with recurrent HGSOC. A total of 2969 DMPs corresponding to 1471 genes were involved in olfactory transduction, and calcium and cAMP signaling. Co-treatment with demethylating agents showed significant growth retardation in ovarian cancer cells through differential inductions, such as cell apoptosis by azacytidine or G2/M cell cycle arrest by decitabine and thioguanine. Notably, azacytidine and decitabine, though not thioguanine, synergistically enhanced cisplatin-mediated cytotoxicity in HGSOC cells. Conclusions: This study demonstrates the significant association of global hypermethylation with poor prognosis and drug resistance in high-grade EOC and highlights the potential of demethylating agents in cancer treatment. [ABSTRACT FROM AUTHOR]