Multimorbidity, healthy lifestyle, and the risk of cognitive impairment in Chinese older adults: a longitudinal cohort study.

BACKGROUND: Evidence on the association between multimorbidity and cognitive impairment in Chinese older population is limited. In addition, whether a healthy lifestyle can protect cognitive function in multimorbid older population remains unknown. METHODS: A total of 6116 participants aged ≥ 65 years from the Chinese Longitudinal Healthy Longevity Survey were followed up repeatedly. The number of coexisting chronic diseases was used for assessing multimorbidity and cardiometabolic multimorbidity. Three lifestyle statuses (unhealthy, intermediate, and healthy) were defined based on a lifestyle score covering smoking, alcohol drinking, body mass index, outdoor activities, and dietary pattern. Cognitive impairment was defined as the Mini-Mental State Examination score < 24. A modified Poisson regression model with robust error variance was used to assess the associations between multimorbidity, healthy lifestyle, and cognitive impairment. RESULTS: During a median follow-up period of 5.8 years, 1621 incident cases of cognitive impairment were identified. The relative risk (RR) of cognitive impairment associated with heavy multimorbidity burden (≥ 3 conditions) was 1.39 (95% confidence interval: 1.22-1.59). This association declined with age, with RRs being 3.08 (1.78-5.31), 1.40 (1.04-1.87), and 1.19 (1.01-1.40) in subjects aged < 70 years, ≥ 70 and < 80 years, and ≥ 80 years, respectively (P for interaction = 0.001). Compared to unhealthy lifestyle, a healthy lifestyle was related to an approximately 40% reduced risk of cognitive impairment regardless of multimorbidity burden. Among the 5 lifestyle factors assessed, daily outdoor activities and a healthy dietary pattern showed convincing protective effects on cognitive function. CONCLUSIONS: The relationship between multimorbidity and cognitive impairment is age-dependent but remains significant in the population aged 80 years or older. A healthy lifestyle may protect cognitive function regardless of the multimorbidity burden. These findings highlight the importance of targeting individuals with heavy multimorbidity burden and promoting a heathy lifestyle to prevent cognitive impairment in Chinese older population.

Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management.

The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.

Phloretin exhibits potential food-drug interactions by inhibiting human UDP-glucuronosyltransferases in vitro.

Phloretin is a well-known apple polyphenol possessing a wide variety of biological effects and has been widely used in many fields. However, it's unclear whether phloretin has an effect on the activity of human UGT enzymes. Our study indicated that phloretin inhibited human UGTs on a broad spectrum. Further kinetic analysis revealed that phloretin inhibited UGT1A1, 1A6, 1A9, 2B7, and 2B15 in a noncompetitive manner, with calculated Ki of 8.34 µM, 16.69 µM, 10.58 µM, 17.74 µM and 2.46µΜ, respectively, whereas phloretin inhibited UGT1A7 in an un-competitive manner, with calculated Ki of 5.70 µM. According to the quantitative risk prediction, co-administration of phloretin with drugs primarily metabolized by UGT1A7 and/or UGT2B15 may result in potential food-drug interactions. To sum up, when phloretin or phloretin-rich food is administered with medications metabolized by UGT1A7 and/or UGT2B15, concern should be exercised.

Potential interactions among myricetin and dietary flavonols through the inhibition of human UDP-glucuronosyltransferase in vitro.

Myricetin is a dietary flavonol and possesses multiple bioactivities, which making it an excellent nutritional supplement and a new drug candidate. However, whether myricetin and other homologous dietary flavonols affect the activities of UDP-glucuronosyltransferases (UGT) enzymes and facilitated food-drug interactions remains unclear. Our results demonstrated that myricetin displayed broad-spectrum inhibition against human UGTs. Myricetin exhibited strong inhibitory effects against UGT1A1, 1A3, 1A6, 1A7, 1A10 (IC50 < 10 µM) with non-competitive inhibition type, while serving as a moderate inhibitor against UGT1A9 and 2B7 (IC50 range from 25 to 29 µM) with competitive and mixed inhibition type, respectively. In Silico docking was carried out to explore the binding models and free energies of myricetin towards inhibitory UGTs. The potential risks of food-drug interactions after myricetin consumption were predicted by combining the in vitro inhibitory data and physiological data. The quantitative prediction in vivo of inhibition on gastrointestinal UGTs by myricetin showed that the inhibition against UGT1A1, 1A3, 1A6, 1A7, 1A9, 1A10 and 2B7 would likely occur with high risk. The follow-up findings demonstrated that morin, kaempferol, quercetin and galangin, the four homologous dietary flavonols, shared similar inhibition patterns towards UGTs. These findings altogether demonstrate that myricetin and homologous dietary flavonols have potent and broad-spectrum inhibitory effects against most human UGTs, thus suggest that much caution should be exercised when flavonols-rich foods or supplements are co-administered with UGT substrate drugs.