Association Between Knowledge and Attitude About Aging and Life Satisfaction Among Older Koreans

SummaryPurposeThe purpose of this study was to measure knowledge and attitude about aging and life satisfaction among older Korean adults and to examine the influence of attitude and knowledge about aging on these adults' life satisfaction.MethodsA cross-sectional and correlational design was used. A total of 405 older adults were surveyed using a written questionnaire at six elderly welfare centers in a metropolitan city in South Korea in mid April 2011. The data were analyzed using descriptive statistics, Pearson's correlation analysis, and multiple regression.ResultsThe score of knowledge on aging was below the medium level. Attitude about aging was neutral, and life satisfaction was at the medium level. Variables such as female sex, age, economic status, monthly allowance, living with a spouse, self-rated overall health, knowledge and attitude about aging accounted for 33.8% of the total variance in predicting life satisfaction of the older adults. Older age and lower economic status reduced life satisfaction. Being female, having a monthly income of 300,000 Korea Republic Won or more, living with a spouse, and better knowledge and attitude about aging were associated with enhanced life satisfaction.ConclusionThe effect of knowledge and attitude about aging on life satisfaction is significant. Economic status, living with a spouse and self-rated overall health status are also predictive factors in life satisfaction. Consequently, nursing interventions for education and psychological support to increase knowledge about aging and induce a positive attitude towards it should be developed to improve older adults' life satisfaction

Intracellular Nanomaterial Delivery via Spiral Hydroporation

In recent nanobiotechnology developments, a wide variety of functional nanomaterials and engineered biomolecules have been created, and these have numerous applications in cell biology. For these nanomaterials to fulfill their promises completely, they must be able to reach their biological targets at the subcellular level and with a high level of specificity. Traditionally, either nanocarrier- or membrane disruption-based method has been used to deliver nanomaterials inside cells; however, these methods are suboptimal due to their toxicity, inconsistent delivery, and low throughput, and they are also labor intensive and time-consuming, highlighting the need for development of a next-generation, intracellular delivery system. This study reports on the development of an intracellular nanomaterial delivery platform, based on unexpected cell-deformation phenomena via spiral vortex and vortex breakdown exerted in the cross- and T-junctions at moderate Reynolds numbers. These vortex-induced cell deformation and sequential restoration processes open cell membranes transiently, allowing effective and robust intracellular delivery of nanomaterials in a single step without the aid of carriers or external apparatus. By using the platform described here (termed spiral hydroporator), we demonstrate the delivery of different nanomaterials, including gold nanoparticles (200 nm diameter), functional mesoporous silica nanoparticles (150 nm diameter), dextran (hydrodynamic diameters between 2–55 nm), and mRNA, into different cell types. We demonstrate here that the system is highly efficient (up to 96.5%) with high throughput (up to 1 × 106 cells/min) and rapid delivery (∼1 min) while maintaining high levels of cell viability (up to 94%)

Spatiotemporally controlled drug delivery via photothermally driven conformational change of self-integrated plasmonic hybrid nanogels

Background Spatiotemporal regulation is one of the major considerations for developing a controlled and targeted drug delivery system to treat diseases efficiently. Light-responsive plasmonic nanostructures take advantage due to their tunable optical and photothermal properties by changing size, shape, and spatial arrangement. Results In this study, self-integrated plasmonic hybrid nanogels (PHNs) are developed for spatiotemporally controllable drug delivery through light-driven conformational change and photothermally-boosted endosomal escape. PHNs are easily synthesized through the simultaneous integration of gold nanoparticles (GNPs), thermo-responsive poly (N-isopropyl acrylamide), and linker molecules during polymerization. Wave-optic simulations reveal that the size of the PHNs and the density of the integrated GNPs are crucial factors in modulating photothermal conversion. Several linkers with varying molecular weights are inserted for the optimal PHNs, and the alginate-linked PHN (A-PHN) achieves more than twofold enhanced heat conversion compared with others. Since light-mediated conformational changes occur transiently, drug delivery is achieved in a spatiotemporally controlled manner. Furthermore, light-induced heat generation from cellular internalized A-PHNs enables pinpoint cytosolic delivery through the endosomal rupture. Finally, the deeper penetration for the enhanced delivery efficiency by A-PHNs is validated using multicellular spheroid. Conclusion This study offers a strategy for synthesizing light-responsive nanocarriers and an in-depth understanding of light-modulated site-specific drug delivery.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (Ministry of Science, ICT and Future Planning, No. 2023R1A2C2003947) for S.L., D.K., H.K., and I.C. This work was supported by the Samsung Research Funding and Incubation Center for Future Technology (SRFC-IT1802-03) for S.L., J.Y., H.K., and I.C. This work was supported by Basic Science Research Program through the NRF funded by the MSIT (No. 2021R1F1A1062856) and was also supported by Regional Innovation Strategy (RIS) through the NRF funded by the Ministry of Education (MOE) (2021RIS-004) for S.K. and J.S

Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19

Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.Peer reviewe

Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models

© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.Alzheimer's disease (AD) is an age-related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD-504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLPAPT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient-derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau-interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLPAPT mice11Nsciescopu

A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood–brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs. © 2021, The Author(s).1

Direct Observation of Defects and Increased Ion Permeability of a Membrane Induced by Structurally Disordered Cu/Zn-Superoxide Dismutase Aggregates

Interactions between protein aggregates and a cellular membrane have been strongly implicated in many protein conformational diseases. However, such interactions for the case of Cu/Zn superoxide dismutase (SOD1) protein, which is related to fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS), have not been explored yet. For the first time, we report the direct observation of defect formation and increased ion permeability of a membrane induced by SOD1 aggregates using a supported lipid bilayer and membrane patches of human embryonic kidney cells as model membranes. We observed that aggregated SOD1 significantly induced the formation of defects within lipid membranes and caused the perturbation of membrane permeability, based on surface plasmon resonance spectroscopy, atomic force microscopy and electrophysiology. In the case of apo SOD1 with an unfolded structure, we found that it bound to the lipid membrane surface and slightly perturbed membrane permeability, compared to other folded proteins (holo SOD1 and bovine serum albumin). The changes in membrane integrity and permeability were found to be strongly dependent on the type of proteins and the amount of aggregates present. We expect that the findings presented herein will advance our understanding of the pathway by which structurally disordered SOD1 aggregates exert toxicity in vivo