Efficiency of PGK1 proteins delivered to the brain via a liposomal system through intranasal route administration for the treatment of spinocerebellar ataxia type 3.

A patient-friendly and efficient treatment method for patients with spinocerebellar ataxia type 3 (SCA3) was provided through a nose-to-brain liposomal system. Initially, PGK1 was overexpressed in HEK 293-84Q-GFP diseased cells (HEK 293-84Q-GFP-PGK1 cells) to confirm its effect on the diseased protein polyQ. A decrease in polyQ expression was demonstrated in HEK 293-84Q-GFP-PGK1 cells compared to HEK 293-84Q-GFP parental cells. Subsequently, PGK1 was encapsulated in a liposomal system to evaluate its therapeutic efficiency in SCA3. The optimized liposomes exhibited a significantly enhanced positive charge, facilitating efficient intracellular protein delivery to the cells. The proteins were encapsulated within the liposomes using an optimized method involving a combination of heat shock and sonication. The liposomal system was further demonstrated to be deliverable to the brain via intranasal administration. PGK1/liposomes were intranasally delivered to SCA3 mice, which subsequently exhibited an amelioration of motor impairment, as assessed via the accelerated rotarod test. Additionally, fewer shrunken morphology Purkinje cells and a reduction in polyQ expression were observed in SCA3 mice that received PGK1/liposomes but not in the untreated, liposome-only, or PGK1-only groups. This study provides a non-invasive route for protein delivery and greater delivery efficiency via the liposomal system for treating neurodegenerative diseases.

Preconditioning of exosomes derived from human olfactory ensheathing cells improved motor coordination and balance in an SCA3/MJD mouse model: A new therapeutic approach.

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.

Predictors of Depression Level among Community-Dwelling Elderly Persons.

Elderly people in the community have difficulty taking care of themselves because of their inability to care for themselves in daily life as well as their poor social support system, which leads to loneliness, resulting in depression. The primary objective was to investigate the level of depression and related factors among community-dwelling elderly persons (CDEP). This was a cross-sectional study, and 150 participants were interviewed. The questionnaires included demographics, the Functional Independence Measure, the Interpersonal Support Evaluation List, the UCLA Loneliness Scale, and the Geriatric Depression Scale Short Form. It was found that participants with different levels of depression accounted for 26%, and education level, living status, chronic disease, daily life function, social support, and loneliness were all significant factors influencing the depression level among the CDEP that could significantly predict 63.4% of the variation in depression level. Nursing staff must understand the level of depression and its influencing factors, encourage the elderly in the community to increase social networks, and integrate leisure into their lives, thereby enhancing the sense of value and meaning of life and reducing feelings of loneliness and depression.

The relationship between infertility family stigma, self-stigma and psychological well-being in female first-visit patients at a reproductive medicine center in Taiwan.

BACKGROUND: Steeped in Chinese culture which considers continuing the family lineage highly important, infertility stigma endorsed by others and oneself can both negatively impact psychological well-being in women with infertility in Taiwan. The aim of the present study was to find out whether family stigma attached to infertility has a direct effect on psychological well-being, or whether it is only when family stigma is internalized into self-stigma that psychological well-being is affected. PARTICIPANTS AND PROCEDURE: The present study had a cross-sectional design, approved by an institutional review board in Taiwan. 245 female participants with infertility completed measures on infertility stigma, self-esteem, and positive and negative affect. The main question of this study was analyzed by conducting structural equation modeling. RESULTS: The present study found that none of the direct effects of family stigma on self-esteem, negative affect, or positive affect were significant, while the indirect effects of family stigma on the three psychological well-being indexes through the mediator of self-stigma were significant. CONCLUSIONS: Self-stigma fully mediates the effect of family stigma on self-esteem, positive affect, and negative affect in women with infertility. Collectively, stigma endorsed by others does not necessarily lead to negative psychological well-being. The negative influence comes from internalizing public/family stigma into self-stigma.