Efficacy of canagliflozin versus metformin in women with polycystic ovary syndrome: A randomized, open-label, noninferiority trial.

OBJECTIVES: To determine the safety and efficacy of canagliflozin in comparison to metformin in polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). METHODS: A single-centre, prospective, randomized open-label (ratio 1:1) noninferiority trial was conducted at the Department of Endocrinology, Shanghai Tenth People's Hospital, between July 2019 and April 2021. Women aged 18 to 45 years with PCOS and IR were enrolled and randomly assigned to either 100 mg (n = 33) canagliflozin daily or 1500 to 2000 mg metformin daily (n = 35) for 12 weeks. The primary outcome was changes in homeostatic model assessment (HOMA)-IR after 12 weeks of treatment. The secondary outcomes included changes in anthropometric measurements, menstrual frequency, sex hormone levels, metabolic variables and body fat distribution. RESULTS: For lowering of HOMA-IR after 12 weeks of treatment, canagliflozin was found to be noninferior to metformin (least-squares mean difference -0.81% [95% confidence interval -2.13 to 0.51]). Both canagliflozin and metformin significantly improved menstrual pattern, reduced body weight and total fat mass, and decreased triglyceride levels. Compared with metformin, canagliflozin had significant advantages in reducing uric acid and dehydroepiandrosterone sulphate levels. Pruritus vulvae (9.09%) and gastrointestinal reaction (55.55%) were the main adverse events in the metformin group and canagliflozin group, respectively. CONCLUSION: This study demonstrates that canagliflozin was not inferior to metformin in PCOS patients with IR, which suggests that sodium-glucose cotransporter-2 inhibitors should be considered as effective drugs in the treatment of PCOS patients with IR.

Dys-psychological Stress Effect on Expressions of P53 and NFκBp65 in Human Ovarian Carcinoma In Vivo.

OBJECTIVE: To investigate the dys-psychological stress effect on the growth of subcutaneous xenotransplanted tumor in nude mice bearing human epithelium ovarian carcinoma, and the influence on P53 and NFκBp65 expressions. METHODS: The subcutaneous tumor xenografts were established by implanting human epithelium ovarian carcinoma tissues into nude mice and the dys-psychological stress model was established with restraint. The mice were randomized into the following four treatment groups with each group six mice respectively: tumor group (group A), normal saline intraperitoneal injection; tumor with stress group (group B), normal saline intraperitoneal injection; tumor therapy group (group C), cisplatin intraperitoneal injection; and tumor therapy with stress group (group D), cisplatin intraperitoneal injection. The expressions of P53 and NFκBp65 in tumor tissues were determined by Western blotting. RESULTS: The expressions of P53 and NFκBp65 in each restraint group were enhanced compared with the control groups (P<0.05). CONCLUSION: The dys-psychological stress may induce the high expressions of P53 and NFκBp65 proteins and further promote tumor growth.

Prediction of the immunological and prognostic value of five signatures related to fatty acid metabolism in patients with cervical cancer.

A growing attention has been attached to the role of fatty acid metabolism (FAM) in the development of cancer, and cervical cancer (CC) is still the primary cause of cancer-associated death in women worldwide. Therefore, it is imperative to explore the possible prognostic significance of FAM in CC. In this study, CC samples and corresponding normal samples were acquired from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Single sample gene set enrichment analysis (ssGSEA) was conducted for calculating FAM-related scores (FAMRs) to screen FAM-related genes (FAMRGs). Two subtypes related to FAM were identified by consistent clustering. Among them, subtype C2 had a poor prognosis, and C1 had a high level of immune cell infiltration, while C2 had a high possibility of immune escape and was insensitive to chemotherapy drugs. Based on the differentially expressed genes (DEGs) in the two subtypes, a 5-gene signature (PLCB4, FBLN5, TSPAN8, CST6, and SERPINB7) was generated by the least absolute shrinkage and selection operator (LASSO) and Akaike information criterion (AIC). The model demonstrated a high prognostic accuracy (area under the curve (AUC)>0.7) in multiple cohorts and was one independent prognostic factor for CC patients. Accordingly, FAMRGs can be adopted as a biomarker for the prediction of CC patients' prognosis and help guide the immunotherapy of CC.

Correlation Between Serum Uric Acid and Body Fat Distribution in Patients With Polycystic Ovary Syndrome.

Objective: This study aims to investigate the correlation between serum uric acid levels and body fat distribution in patients with polycystic ovary syndrome (PCOS). Methods: Between May 2017 and March 2021, a total of 199 patients with PCOS were recruited from the Department of Endocrinology and Metabolism at the Shanghai Tenth People's Hospital. Anthropometric characteristics, metabolic parameters, and reproductive hormones were measured. Hyperuricemia was defined as serum uric acid (SUA) greater than 420 µmol/l. Dual-energy X-ray absorptiometry (DEXA) was used to measure body fat distribution. Results: The prevalence of hyperuricemia in patients with PCOS was 28.64%. PCOS patients with hyperuricemia are more obese and have a higher waist-to-hip ratio (WHR) and worse lipid metabolism than those without hyperuricemia. According to SUA quartiles, patients in the highest quartile had higher total testosterone (TT), body fat accumulation, and lower sex hormone-binding globulin (SHBG) than patients in the lowest quartile. SUA was correlated with percentage of total body fat, arm fat mass, leg fat mass, trunk fat mass, android/gynoid (A/G) ratio, and visceral adipose tissue (VAT) mass. After controlling possible confounders, logistic regression analysis found that only excessive VAT mass could significantly increase the risk of hyperuricemia in patients with PCOS. Conclusion: In patients with PCOS, a high level of VAT mass, but not other fat compartments, will exacerbate the risk of hyperuricemia. Attention should be paid to the role of excessive VAT in the occurrence and development of PCOS with hyperuricemia.

Ino80 promotes cervical cancer tumorigenesis by activating Nanog expression.

Ino80 ATPase is an integral component of the INO80 ATP-dependent chromatin-remodeling complex, which regulates transcription, DNA repair and replication. We found that Ino80 was highly expressed in cervical cancer cell lines and tumor samples. Ino80 knockdown inhibited cervical cancer cell proliferation, induced G0/G1 phase cell cycle arrest in vitro and suppressed tumor growth in vivo. However, Ino80 knockdown did not affect cell apoptosis, migration or invasion in vitro. Ino80 overexpression promoted proliferation in the H8 immortalized cervical epithelial cell line, which has low endogenous Ino80 expression as compared to cervical cancer cell lines. Ino80 bound to the Nanog transcription start site (TSS) and enhanced its expression in cervical cancer cells. Nanog overexpression in Ino80 knockdown cell lines promoted cell proliferation. This study demonstrated for the first time that Ino80 was upregulated in cervical cancer and promoted cell proliferation and tumorigenesis. Our findings suggest that Ino80 may be a potential therapeutic target for the treatment of cervical cancer.