Maternal Folic Acid Supplementation during Pregnancy Prevents Hepatic Steatosis in Male Offspring of Rat Dams Fed High-Fat Diet, Which Is Associated with the Regulation of Gut Microbiota.

Maternal dietary patterns during pregnancy have been demonstrated to impact the structure of the gut microbiota in offspring, altering their susceptibility to diseases. This study is designed to elucidate whether the impact of folic acid supplementation during pregnancy on hepatic steatosis in male offspring of rat dams exposed to a high-fat diet (HFD) is related to gut-liver axis homeostasis. In this study, female rats were administered a HFD and simultaneously supplemented with 5 mg/kg folic acid throughout their pregnancy. Histopathological examination showed that folic acid supplementation effectively ameliorated hepatic lipid accumulation and inflammatory infiltrate in male offspring subjected to a maternal HFD. Maternal folic acid supplementation reduced the abundance of Desulfobacterota and the Firmicutes/Bacteroidota (F/B) ratio in male offspring. The expression of tight junction proteins in the colon was significantly upregulated, and the serum LPS level was significantly reduced. Furthermore, there was a notable reduction in the hepatic expression of the TLR4/NF-κB signaling pathway and subsequent inflammatory mediators. Spearman's correlation analysis revealed significant associations between hepatic inflammation-related indices and several gut microbiota, particularly Desulfobacterota and Lactobacillus. With a reduction in hepatic inflammation, the expression of PPAR-α was upregulated, and the expression of SREBP-1c and its downstream lipid metabolism-related genes was downregulated. In summary, folic acid supplementation during pregnancy modulates gut microbiota and enhances intestinal barrier integrity in male offspring of HFD dams. This helps reduce the LPS leakage and suppress the expression of TLR4/NF-κB pathway in the liver, thereby improving lipid metabolism disorders, and alleviating hepatic steatosis.

Dietary Folic Acid Supplementation Attenuates Maternal High-Fat Diet-Induced Fetal Intrauterine Growth Retarded via Ameliorating Placental Inflammation and Oxidative Stress in Rats.

The placenta is particularly susceptible to inflammation and oxidative stress, leading to placental vascular dysfunction and placental insufficiency, which is associated with fetal intrauterine growth restriction (IUGR). It is unknown whether folic acid (FA) supplementation can alleviate high-fat diet-induced IUGR in rats by improving placental function. In this study, pregnant rats were randomized into one of four diet-based groups: (1) control diet (CON), (2) control diet supplemented with FA, (3) high-fat diet (HFD), and (4) high-fat diet supplemented with FA (HFD + FA). Dams were sacrificed at gestation day 18.5 (GD18.5). The results indicated that dietary FA supplementation normalized a maternal HFD-induced decrease in fetal weight. The decrease in placental efficiency, labyrinth zone (LZ) area, blood sinusoid area, vascular density, and the levels of angiogenesis factors induced by a maternal HFD were alleviated by the addition of FA, suggesting that FA supplementation can alleviate placental vascular dysplasia. Furthermore, FA supplementation increased the protein expressions of SIRT1, inhibited NF-κB transcriptional activation, attenuated the levels of NF-κB/downstream pro-inflammatory cytokines, induced Nrf2 activation, and increased downstream target protein expression. In conclusion, we found that dietary FA supplementation during pregnancy could improve maternal HFD-induced IUGR by alleviating placental inflammation and oxidative stress, which may be associated with the regulation of SIRT1 and its mediated NF-κB and Nrf2 signaling pathways.

Competing risk analysis of cardiovascular death in patients with primary gallbladder cancer.

BACKGROUND: Developments in medical technology are resulting in continuous decreases in the cancer mortality rate of patients with gallbladder cancer, while non-cancer deaths in cancer patients are becoming more common. The main cause of this is cardiovascular mortality (CVM). The purpose of this study was to determine the CVM risk in patients with primary gallbladder cancer (PGC). METHODS: We extracted information on patients in the SEER database who were diagnosed with PGC from 2004 to 2015, compared CVM in patients with PGC with the general United States population, and calculated standardized mortality rates (SMRs) and the absolute excess risk. A competing risks model was used to identify and analyze the independent risk factors for cardiovascular death in patients with PGC. RESULTS: This study included 5925 patients, 247 of whom died from cardiovascular disease. The SMR of cardiovascular death in patients with PGC was 15.84 (95% confidence interval: 15.83-15.85), and the SMR was slightly lower in male than female patients. The competing risks analysis indicated that age, marital status, cancer cell differentiation, chemotherapy status, and year of diagnosis were risk factors for cardiovascular death in patients with PGC. CONCLUSIONS: The CVM risk is considerably higher in patients with PGC than in the general population. It is therefore very necessary to apply cardioprotective interventions to patients with PGC.

Metformin Protects Cardiovascular Health in People With Diabetes.

Background: Metformin is the most commonly used drug for patients with diabetes, but there is still some controversy about whether it has a protective effect on cardiovascular health. We therefore used the National Health and Nutritional Examination Survey (NHANES) database to analyze the impact of metformin use on cardiovascular health in patients with diabetes. Methods: We extracted the demographic data and laboratory test results of all people with diabetes in the NHANES database from January 2017 to March 2020. The outcomes were seven indicators of cardiovascular health from the American Heart Association, each was scored as 0, 1, and 2 to represent poor, moderate, and ideal health statuses, respectively. The scores for the indicators (excluding diet and glycemic status) were summed, and the sum score was then considered to indicate unhealthy (0-5) or healthy (>5). Multivariate logistic regression analysis was used, and subgroup analyses were performed by age, alcohol consumption, education, and marital status. Results: This study included 1,356 patients with diabetes, among which 606 were taking metformin. After adjusting for all included variables, oral metformin in patients with diabetes had a protective effect on the cardiovascular health of patients (OR = 0.724, 95% CI = 0.573-0.913, P = 0.007). Subgroup analysis indicated that metformin protects the cardiovascular health of people with diabetes more clearly in those who are young (OR = 0.655, 95% CI = 0.481-0.892, P = 0.007), married (OR = 0.633, 95% CI = 0.463-0.863, P = 0.003), and drink alcohol (OR = 0.742, 95% CI = 0.581-0.946, P = 0.016). Conclusion: This study found that metformin has a protective effect on the cardiovascular health of patients with diabetes. The study findings support the general applicability of metformin.