ABSTRACT
Purpose: Trimethylamine N-oxide (TMAO) is a metabolite of phosphatidylcholine in red meat and other diets, which is associated with cardiovascular and other diseases. The aim of this study is to evaluate the associations of serum TMAO with mild cognitive impairment (MCI) in the Chinese type 2 diabetes mellitus (T2DM) population. Materials and Methods: A total of 253 hospitalized T2DM patients and 150 healthy controls were included in this cross-sectional study. Montreal Cognitive Assessment (MoCA) assessed the cognition function, and the 253 T2DM patients were divided into 74 subjects with MCI and 179 with non-MCI. Demographic data and biochemical test results were evaluated. Serum TMAO level was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: A higher serum TMAO level was observed in T2DM patients compared with the healthy controls (P < 0.001). Among all T2DM patients, the MCI group (n = 74) showed higher serum TMAO levels than the non-MCI group. Spearman correlation test showed that TMAO levels were significantly positively correlated with age (r = 0.147, P = 0.019), body mass index (BMI) (r = 0.153, P = 0.015), diabetes duration (r = 0.160, P = 0.011), HbA1c (r = 0.138, P = 0.029), triglyceride (TG) (r = 0.138, P = 0.029), creatinine (r = 0.184, p = 0.003), hs-CRP (r = 0.243, P < 0.001), and were negatively correlated with HDL-C (r = -0.144, P = 0.022), BDNF (r = -0.165, p = 0.009), and MoCA (r = -0.386, P < 0.001) score (all P < 0.05). Multivariable Logistic regression identified high serum TMAO level as a significant independent factor of MCI in the T2DM patients (OR = 1.404, 95% CI = 1.255-1.571; P < 0.001). Conclusion: Our study showed that T2DM patients with MCI have elevated serum TMAO levels.
ABSTRACT
γ-Cyclodextrin metal-organic frameworks (γCDMOF) recently emerged as biofriendly, highly porous, and crystalline materials with potential applications in drug delivery. However, little is known about their drug entrapment and release characteristics, which are key parameters in the design of drug carriers. The macroscopic properties of a material are determined by its microstructure. Thus, the characteristics of the constitutive units of the cubic crystalline γCDMOF determine their drug loading and release behaviors. In this study, the release profile of prednisolone (PNS) form γCDMOF was predicted, and the mechanism was analyzed based on the γCDMOF molecular structure. For the first time, experimental, molecular simulation, and mathematical modeling methods were combined to gain insights into the drug distribution in cubic porous crystals of γCDMOF as well as on drug release kinetics. The predicted release profile was in good agreement with the experimental results, showing that the modeling method was reliable. The methodology developed here could provide a reference for further investigations of drug penetration and release in supramolecular systems.
