Investigating the causal impact of polycystic ovary syndrome on gestational diabetes mellitus: a two-sample Mendelian randomization study.

Introduction: Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention and treatment. Despite numerous observational studies suggesting an association between PCOS and GDM, it remains unclear whether a definitive causal relationship exists between these two conditions and which specific features of PCOS contribute to increased incidence of GDM. Methods: The causal relationship between polycystic ovary syndrome (PCOS), its characteristic indices, and gestational diabetes mellitus (GDM) was investigated using a two-sample Mendelian randomization study based on publicly available statistics from genome-wide association studies (GWAS). The inverse-variance weighted method was employed as the primary analytical approach to examine the association between PCOS, its characteristic indices, and GDM. MR Egger intercept was used to assess pleiotropy, while Q values and their corresponding P values were utilized to evaluate heterogeneity. It is important to note that this study adopts a two-sample MR design where PCOS and its characteristic indices are considered as exposures, while GDM is treated as an outcome. Results: The study results indicate that there is no causal relationship between PCOS and GDM (all methods P > 0.05, 95% CI of OR values passed 1). The IVW OR value was 1.007 with a 95% CI of 0.906 to 1.119 and a P value of 0.904. Moreover, the MR Egger Q value was 8.141 with a P value of 0.701, while the IVW Q value was also 8.141 with a P value of 0.774, indicating no significant heterogeneity. Additionally, the MR Egger intercept was 0.0004, which was close to zero with a P value of 0.988, suggesting no pleiotropy. However, the study did find a causal relationship between several other factors such as testosterone, high-density lipoprotein, sex hormone-binding globulin, body mass index, waist-hip ratio, apolipoprotein A-I, number of children, diabetes illnesses of mother, father and siblings, hemoglobin A1c, fasting insulin, fasting blood glucose, years of schooling, and GDM based on the IVW method. Conclusion: We observed no association between genetically predicted PCOS and the risk of GDM, implying that PCOS itself does not confer an increased susceptibility to GDM. The presence of other PCOS-related factors such as testosterone, high-density lipoprotein, and sex hormone-binding globulin may elucidate the link between PCOS and GDM. Based on these findings, efforts aimed at preventing GDM in individuals with PCOS should prioritize those exhibiting high-risk features rather than encompassing all women with PCOS.

The inhibition of trans-cinnamaldehyde on the virulence of Candida albicans via enhancing farnesol secretion with low potential for the development of resistance.

The emergence of drug resistance and limitation of antifungal agents complicate the management of fungal infection. Candida albicans, as the most common fungal infection pathogen, causes candidiasis via developing its virulence factors. In this study, we found trans-cinnamaldehyde (TC), known as a "Generally Regarded As Safe" (GRAS) molecule, had moderate antifungal activities against various Candida species and could retard the virulence of C. albicans in a dose-dependent manner by inhibiting the adhesion, morphological transition and biofilms formation. The mechanisms investigation revealed that the inhibition of hyphae and biofilms development was caused by the increasing farnesol secretion induced by Dpp3 expression. Since drug resistance restricted the treatment of clinical fungal infection, we explored the capacity of TC to develop drug-resistance under a long time TC treatment. Results showed that TC had little chance to form resistance by a serial passage experiment. Our work illustrates the underlying mechanism of TC inhibition of morphological transition and provides a optional application in treating the relevant fungal infections by targeting fungal virulence factors.