Causal relationship between affect disorders and endometrial cancer: a Mendelian randomisation study.

BACKGROUND: The aim was to assess the causal relationship between depression and anxiety disorders and endometrial cancer. METHOD: We performed two-sample Mendelian randomisation analysis using summary statistics from genome-wide association studies to assess associations of major depressive disorder, anxiety and stress-related disorders with endometrial cancer. The genome-wide association studies(GWASs) data were derived from participants of predominantly European ancestry included in the Genome-wide Association Research Collaboration. Inverse variance-weighted, MR-Egger and weighted median MR analyses were performed, together with a range of sensitivity analyses. RESULTS: Mendelian randomisation analysis showed no statistically significant genetic responsibility effect of anxiety and stress-related disorders on any pathological type of endometrial cancer. Only the effect of major depressive disorder under the inverse variance weighting method increasing the risk of endometrial endometrial cancer (effect 0.004 p = 0.047) and the effect of major depressive disorder under the MR-Egger method decreasing endometrial cancer of all pathology types (effect -0.691 p = 0.015) were statistically significant. Other Mendelian randomisation analyses did not show a statistically significant effect. CONCLUSION: Major depressive disorder(MDD), anxiety and stress-related disorders(ASRD) are not genetically responsible for endometrial cancer. We consider that emotional disorders may affect endometrial cancer indirectly by affecting body mass index. This study provides us with new insights to better understand the aetiology of endometrial cancer and inform prevention strategies.

This study used public genomic data to analyse association between affective disorders, including depression and anxiety, and endometrial cancer. Genes treated as instrumental variables help us understand the causal link between affective disorders and endometrial cancer through bioinformatics. In addition to this, we added type 2 diabetes, body mass index, polycystic ovary syndrome, and age at menopause for multivariate Mendelian randomisation analyses with the aim of reducing confounding bias. Because we consider these factors may potentially influence the relationship between affective disorders and endometrial cancer. Ultimately we believe that the association between depression and endometrial cancer is not as strong as that of obesity, due to the genetic correlation between depression and obesity.

Psychological factors increase the risk of ovarian cancer.

This study evaluated whether psychological stress increases the incidence of ovarian cancer. A literature search of the electronic databases PubMed and Web of Science from the date of inception to August 2022 was undertaken. Studies with data on psychosocial factors associated with ovarian cancer incidence were included in this study. A random-effect model meta-analysis was undertaken to estimate these data. We used subgroup analysis to adjust for heterogeneity. A total of 4 articles, 10 sets of data, 8 cohort studies, and 2 case-control studies from 682 records were included in this review. Meta-analyses of the included cohort study subgroups suggested that psychological factors increase the risk of ovarian cancer (effect size = 1.37, 95% CI: 1.20-1.53); the subgroup of case-control studies suggested that psychological factors did not increase ovarian cancer risk (effect size = 0.84, 95% CI: 0.70-0.98). These findings indicate that psychological stress is a possible new risk factor for ovarian cancer.Prospero registration number: CRD42022357983IMPACT STATEMENTWhat is already known on this subject? Psychological stress has been shown to increase the risk of many diseases. The relationship between psychological stress and the incidence of ovarian cancer has not been confirmed.What do the results of this study add? The effect of psychological stress on the risk of ovarian cancer was estimated using meta-analysis as an overall ratio.What are the implications of these findings for clinical practice and/or further research? Relaxing psychological stress and appropriate psychotherapy in clinical settings can help reduce the risk of ovarian cancer.

RHPN2 Promotes Malignant Cell Behaviours in Ovarian Cancer by Activating STAT3 Signalling.

BACKGROUND: Ovarian cancer is the fifth most common cause of cancer-related deaths and accounts for 3% of cancer cases occurring in women. Therefore, determining the underlying genes that can promote ovarian cancer progression is of great urgency. It has been reported that RHPN2 promotes tumour progression in various types of cancer, but its role in ovarian cancer pathogenesis remains unknown. MATERIALS AND METHODS: In this study, bioinformatic datasets were used to predict the expression of RHPN2 in clinical samples and determine the relationship between RHPN2 and the prognosis of ovarian cancer patients. Clinical samples were used to verify the prediction. RHPN2-targeting shRNA was used to investigate the effect of RHPN2 on ovarian cancer cells, and following RHPN2 knockdown, the proliferative and migratory capacities of ovarian cancer cells were tested. To determine the downstream signalling target of RHPN2, a luciferase reporter assay was conducted, and an animal experiment was carried out to confirm the effect of RHPN2 in vivo. RESULTS: The public datasets indicated that ovarian cancer tissues showed significantly higher RHPN2 expression than para-cancer normal tissues, and poor prognosis was observed in patients with higher RHPN2 expression, which was further confirmed in clinical samples. After RHPN2 was knocked down, the proliferation and migration of ovarian cancer cells were significantly impaired; a luciferase reporter assay indicated that the STAT3 signalling pathway was the most highly affected, and RHPN2 downregulation inhibited STAT3 nuclear translocation. STAT3 inhibitors partially rescued the tumour-promoting effect induced by RHPN2 overexpression, which was further confirmed by animal experiments. CONCLUSION: Collectively, our results indicate that RHPN2 promotes malignant behaviours in ovarian cancer by activating STAT3 signalling.

Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK.

BACKGROUND: Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which influences the health of maternal-child in clinical practice. It is still urgent to develop new effective treatment for GDM. Naringenin is a bioactive ingredient with multiple activities including anti-diabetic. In current study, the effects of naringenin on GDM symptoms, insulin tolerance, inflammation, and productive outcomes were evaluated and the underlying mechanisms were explored. METHODS: We administrated naringenin to GDM mice and monitored the GDM symptoms, glucose and insulin tolerance, inflammation and productive outcomes. We established tumor necrosis factor alpha (TNF-α)-induced insulin resistance skeletal muscle cell model and evaluated the effects of naringenin on reactive oxygen species (ROS) production, glucose uptake and glucose transporter type 4 (GLUT4) membrane translocation. RESULTS: We found that naringenin ameliorated GDM symptoms, improved glucose and insulin tolerance, inhibited inflammation, and improved productive outcomes. It was further found that naringenin inhibited TNF-α-induced ROS production, enhanced GLUT4 membrane translocation, and glucose uptake, which were abolished by inhibition of AMP-activated protein kinase (AMPK). CONCLUSION: Naringenin improves insulin sensitivity in gestational diabetes mellitus mice in an AMPK-dependent manner.