Frailty and psychiatric disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.

Causal effects of gut microbiota on sepsis: a two-sample Mendelian randomization study.

Background: Recent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear. Methods: The present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS (N = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and the genome-wide statistical significance threshold (5 × 10-8) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran's Q test, and leave-one-out test, were carried out to assess the robustness of our findings. Results: Our study suggested that increased abundance of Deltaproteobacteria, Desulfovibrionales, Catenibacterium, and Hungatella were negatively associated with sepsis risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group, and Terrisporobacter were positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy. Conclusion: This study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment.

[Determination of apparent oil-water partition coefficient of andrographolide and dehydroandrographolide and effect of pH on them].

OBJECTIVE: To determine the apparent n-octanol-water/buffer partition coefficient of andrographolide and dehydroandrographolide. METHODS: The apparent n-octanol-water/buffer partition coefficients of andrographolide and dehydroandrographolide were measured by shaking flask method. The concentrations of andrographolide and dehydroandrographolide were analyzed by HPLC method. RESULTS: The Papp of andrographolide and dehydroandrographolide were 3.90 (log Papp = 0.59) and 19.75 (log Papp = 1. 30) in water at 37 degrees C, respectively. CONCLUSIONS: The apparent n-octanol-buffer partition coefficients of andrographolide and dehydroandrographolide are influenced by pH, and the higher pH may decrease the apparent n-octanol-buffer partition coefficients of them. Andrographolide has the highest partition coefficient in pH6, and dehydroandrogapholide in pH5.