RESUMEN
Exon skipping is an efficient technique to inhibit specific gene expression induced by a short-sequence peptide nucleic acid (PNA).To date, there has been no study on the effects of PNA on skin pigmentation. In melanocytes, the tripartite complex is responsible for the transport of mature melanosomes from the nucleus to the dendrites. The tripartite complex is composed of Rab27a, Mlph (Melanophilin), and Myosin Va. Defects in the protein Mlph, a melanosome transport-related protein, are known to cause hypopigmentation. Our study shows that Olipass peptide nucleic acid (OPNA), a cell membrane-permeable PNA, targets exon skipping in the Mlph SHD domain, which is involved in Rab27a binding. Our findings demonstrate that OPNA induced exon skipping in melan-a cells, resulting in shortened Mlph mRNA, reduced Mlph protein levels, and melanosome aggregation, as observed by microscopy. Therefore, OPNA inhibits the expression of Mlph by inducing exon skipping within the gene. These results suggest that OPNA, which targets Mlph, may be a potential new whitening agent to inhibit melanosome movement.
RESUMEN
Objectives@#This study investigated the effect of cognitive impairment on the association between social network properties and mortality among older Korean adults. @*Methods@#This study used data from the Korean Social Life, Health, and Aging Project. It obtained 814 older adults’ complete network maps across an entire village in 2011-2012. Participants’ deaths until December 31, 2020 were confirmed by cause-of-death statistics. A Cox proportional hazards model was used to assess the risks of poor social network properties (low degree centrality, perceived loneliness, social non-participation, group-level segregation, and lack of support) on mortality according to cognitive impairment. @*Results@#In total, 675 participants (5510.4 person-years) were analyzed, excluding those with missing data and those whose deaths could not be verified. Along with cognitive impairment, all social network properties except loneliness were independently associated with mortality. When stratified by cognitive function, some variables indicating poor social relations had higher risks among older adults with cognitive impairment, with adjusted hazard ratios (HRs) of 2.12 (95% confidence interval [CI], 1.34 to 3.35) for social nonparticipation, 1.58 (95% CI, 0.94 to 2.65) for group-level segregation, and 3.44 (95% CI, 1.55 to 7.60) for lack of support. On the contrary, these effects were not observed among those with normal cognition, with adjusted HRs of 0.73 (95% CI, 0.31 to 1.71), 0.96 (95% CI, 0.42 to 2.21), and 0.95 (95% CI, 0.23 to 3.96), respectively. @*Conclusions@#The effect of social network properties was more critical among the elderly with cognitive impairment. Older adults with poor cognitive function are particularly encouraged to participate in social activities to reduce the risk of mortality.
RESUMEN
The Korean Social Life, Health, and Aging Project (KSHAP) is a population-based longitudinal study of health determinants among elderly Koreans. The target population of the KSHAP are people aged 60 years or older and their spouses living in a rural community of Korea. A complete enumeration survey was conducted in the first wave of the KSHAP on 94.7% (814 of 860) of the target population between December 2011 and July 2012. The KSHAP-Health Examination (KSHAP-HE) cohort consists of 698 people who completed additional health examinations at a public health center (n=533) or at their home (n=165). Face-to-face questionnaires were used to interview participants on their demographics, social network characteristics, medical history, health behaviors, cognitive function, and depression symptoms. Health center examinations included anthropometric measures, body impedance analysis, resting blood pressure measurement, radial artery tonometry, bone densitometry, the timed up-and-go test, and fasting blood analysis. However, only anthropometric measures, blood pressure measurement, and non-fasting blood analysis were available for home health examinations. Collaboration is encouraged and access to the KSHAP baseline data will be available via the website of the Korean Social Science Data Archive (http://www.kossda.or.kr).