Smart antioxidant function enhancing(SAFE)nucleic acid therapy for ROS-related chronic diseases and comorbidities

Reactive oxygen species(ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders.The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system.However,ROS under redox homeostasis regulates a wide range of life activities.Therefore,smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely.This study reports a smart antioxidant function enhancement(SAFE)strategy.On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system,thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner.Through structural modulation and ligand modification,we develop SAFE nanoparticles based on nanohybrid complexes(SAFE-complex)adapted to brain delivery of nucleic acid drugs.SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage.Moreover,SAFE-complex can stabilize storage in the form of freeze-dried powder.These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.

Associations of socioeconomic status with infectious diseases mediated by lifestyle, environmental pollution and chronic comorbidities: a comprehensive evaluation based on UK Biobank

Background Socioeconomic status(SES)inequity was recognized as a driver of some certain infectious diseases.However,few studies evaluated the association between SES and the burden of overall infections,and even fewer identified preventable mediators.This study aimed to assess the association between SES and overall infectious diseases burden,and the potential roles of factors including lifestyle,environmental pollution,chronic disease history.Methods We included 401,009 participants from the UK Biobank(UKB)and defined the infection status for each participant according to their diagnosis records.Latent class analysis(LCA)was used to define SES for each participant.We further defined healthy lifestyle score,environment pollution score(EPS)and four types of chronic comorbidities.We used multivariate logistic regression to test the associations between the four above covariates and infectious diseases.Then,we performed the mediation and interaction analysis to explain the relationships between SES and other variables on infectious diseases.Finally,we employed seven types of sensitivity analyses,including considering the Townsend deprivation index as an area level SES variable,repeating our main analysis for some individual or composite factors and in some subgroups,as well as in an external data from the US National Health and Nutrition Examination Survey,to verify the main results.Results In UKB,60,771(15.2%)participants were diagnosed with infectious diseases during follow-up.Lower SES[odds ratio(OR)=1.5570]were associated with higher risk of overall infections.Lifestyle score mediated 2.9%of effects from SES,which ranged from 2.9 to 4.0%in different infection subtypes,while cardiovascular disease(CVD)mediated a proportion of 6.2%with a range from 2.1 to 6.8%.In addition,SES showed significant negative interaction with lifestyle score(OR=0.8650)and a history of cancer(OR=0.9096),while a significant synergy interaction was observed between SES and EPS(OR=1.0024).In subgroup analysis,we found that males and African(AFR)with lower SES showed much higher infection risk.Results from sensitivity and validation analyses showed relative consistent with the main analysis.Conclusions Low SES is shown to be an important risk factor for infectious disease,part of which may be mediated by poor lifestyle and chronic comorbidities.Efforts to enhance health education and improve the quality of living environment may help reduce burden of infectious disease,especially for people with low SES.