RESUMO
BACKGROUND: Defined clinically by elevated blood pressure along with either proteinuria and/or maternal organ dysfunction, representing a major cause of morbidity and mortality pregnant women and newborns. Metformin (MET), an oral antidiabetic medication, has been shown to prevent preeclampsia (PE) through various mechanisms, including reducing inflammation, improving endothelial dysfunction, improving mitochondrial function, and altering cellular homeostasis and energy metabolism. Herein, we explored the role of MET in PE and its underlying molecular mechanisms using in in vivo experiments. METHODS: RT-qPCR, Western blot (WB), and immunohistochemistry (IHC) were conducted to assess the mRNA or protein expression of genes related to mitochondrial apoptosis. Additionally, ELISA was conducted to quantify the expression of mitochondrial apoptosis and inflammation-related genes, as well as PE biomarkers. RESULTS: Treatment with MET in PE rats ameliorated hypertension and proteinuria, altered the expression of PE biomarkers, and significantly inhibited L-NAME-induced inflammation and cell apoptosis. MET modulated the levels of inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10, mitigating inflammation in PE rats. Furthermore, MET regulated mitochondrial outer membrane permeability (MOMP), thereby reducing cell apoptosis occurring in the mitochondrial pathway of PE rats. CONCLUSIONS: This study demonstrates that MET alleviates inflammation and cell apoptosis in PE rats by modulating the expression of inflammatory factors and MOMP. Our results indicate that MET has huge therapeutic potential against PE.
RESUMO
BACKGROUD: Previous observational studies have shown that vitiligo usually co-manifests with a variety of dysglycemic diseases, such as Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). Mendelian randomization (MR) analysis was performed to further evaluate the causal association between fasting plasma glucose, glycosylated hemoglobin (HbA1c), T1DM, T2DM and vitiligo. MATERIALS AND METHODS: We used aggregated genome-wide association data from the Integrative Epidemiology Unit (IEU) online database of European adults vitiligo; HbA1c data were from IEU. Fasting blood glucose data were obtained from the European Bioinformatics Institute (EBI). T1DM and T2DM data were from FinnGen. We used bidirectional two-sample and multivariate MR analyses to test whether dysglycemic measures (fasting blood glucose, HbA1c), diabetes-related measures (T1DM, T2DM) are causatively associated with vitiligo. Inverse variance weighting (IVW) method was used as the main test method, MR-Egger, Weighted mode and Weighted median were used as supplementary methods. RESULTS: We found no statistically significant evidence to support a causal association between dysglycemic traits and vitiligo, but in the correlation analysis of diabetic traits, our data supported a positive causal association between T1DM and vitiligo (p = 0.018). In the follow-up multivariate MR analysis, our results still supported this conclusion (p = 0.016), and suggested that HbA1c was not a mediator of T1DM affecting the pathogenesis of vitiligo. No reverse causality was found in any of the reverse MR Analyses of dysglycemic traits and diabetic traits. CONCLUSIONS: Our findings support that T1DM is a risk factor for the development of vitiligo, and this conclusion may explain why the co-presentation of T1DM and vitiligo is often seen in observational studies. Clinical use of measures related to T1DM may be a new idea for the prevention or treatment of vitiligo.