ABSTRACT
The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.
ABSTRACT
Objective To investigate the association of serum uric acid level with glomerular filtration rate and explore the predictive value of the physiological uric acid levels for reduced renal function.Methods A total of 6 532 subjects from Karemary community and 2 402 subjects from the First Affiliated Hospital of Xinjiang Medical University were enrolled.All subjects were surveyed with questionnaire and their serum biochemical indices and liver functions were measured.Meanwhile,a cohort study was conducted,752 subjects with normal renal function were selected from young and middle-aged healthy people in 2008.During the 3-year follow-up,the incidence of reduced renal function and the risk factors of estimated glomerular filtration rate (eGFR) were analyzed.Results Serum uric acid (SUA) was the independent risk factor of reduced GFR in cross-sectional analysis.The 2 groups were stratified by sex and age,except for female population over 45 years old in the first group,the level of physiological serum uric acid was the risk factor for decreased eGFR in the rest of groups.During 3-year follow-up,the incidence of reduced renal function was 15.40％ and SUA was the independent risk factor of decreased eGFR.Conclusions The concentration of physiological serum uric acid was closely related with renal function,and the increase in SUA whthin normal range had an important early predictive value for decreased GFR.