Sleep and Caregiver Burden Among Caregivers of Persons Living With Dementia: A Scoping Review.

Background and Objectives: Caregivers of persons with dementia report worse sleep when compared to the general population. The objective of this review was to synthesize evidence regarding the link between caregiver burden and dementia caregivers' sleep. Research Design and Methods: We conducted a scoping review using a systematic search for pertinent literature in PubMed, CINAHL, and Web of Science through March 2022. Keywords included content areas of dementia, caregiver burden, and sleep. Inclusion criteria were informal caregivers of persons living with dementia, a measured relationship between informal dementia caregiver sleep and subjective caregiver burden variables, and original research. Non-English studies were excluded. Extracted data were organized in tables, compared, and synthesized. Results: The search yielded 540 nonduplicate articles screened by title and abstract; 118 full-text articles were reviewed; 24 were included. Most studies were cross-sectional, with variable sample sizes. Dementia caregivers had significantly poorer overall perceived sleep than noncaregivers across 4 studies that examined self-reported sleep measures. Eighteen studies investigated the association between caregiver burden and self-reported sleep quality, with 14 reporting a significant positive association between caregiver burden and self-reported sleep quality, and 4 finding null results. Only 2 of the 4 studies reporting the association between caregiver burden and objective sleep parameters (ie, actigraphy and polysomnography) reported a significant positive association for at least one sleep subdomain. Discussion and Implications: Although subjective sleep quality is commonly affected by dementia caregiving burden, there is a lack of corresponding evidence on the relationship between burden and objective sleep metrics. Healthcare providers should consider the dementia caregiver burden's impact on sleep and regularly assess caregivers' sleep difficulties. Future studies should focus on consistently measuring caregiver burden and sleep to promote dementia caregiver health and well-being.

The relationship between social support and sleep quality in older adults: A review of the evidence.

OBJECTIVES: Sleep quality is crucial for the health and well-being of older adults, and social support has been consistently shown to be related to sleep quality. However, there is a need for research to understand the mechanisms through which these two factors are linked. The purpose of this review is to synthesize scientific literature on the relationship between social support and sleep quality in older adults. METHODS: Using an integrative review method, this review was conducted for a period from January 2012 to November 2022 using a combination of keywords related to social support and sleep quality in older adults. RESULTS: A total of 21 studies that met the inclusion criteria were included. Social support was found to have a positive relationship with subjective and objective sleep quality. It may act as both a mediator between insomnia and hopelessness and a moderator buffering the influence of rumination and negative emotions on sleep quality. CONCLUSION: This review provides evidence for the positive relationship between social support and sleep quality in older adults. Based on the findings of this review, healthcare professionals should prioritize incorporating assessments of social support and implementing interventions aimed at enhancing social support in older adults to improve their sleep quality.

Chemical characterization and biological activity data for a novel indirubin derivative, LDD-1819.

This article contains chemical characterization and biological activity data for a novel indirubin derivative, termed LDD-1819. The detailed synthesis procedure and associated NMR data are presented. The concentration-dependent inhibition data of two biological targets, glycogen synthase kinase-3 ß and aurora kinase A are described. The following biological data are also contained in this article: 1) the cellularization of skeletal muscle myotubes by LDD-1819 or two small molecule inhibitors of glycogen synthase kinase-3 ß and aurora kinase A (BIO and reversine) and gene expression data for the myoblast markers Pax-7 and Myf5, 2) Cell viability of hTERT human immortalized fibroblasts, colon cancer cells and breast cancer cells, and 3) Western blotting analysis of full length and cleaved caspse-7, and cleaved poly (ADP-ribose) polymerase (PARP) in hTERT fibroblasts treated with LDD-1819. A schematic diagram of the biological activities of LDD-1819 is also presented. Further interpretation and discussion of these data are provided in the associated research article 'A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity' (Kim et al., 2019).

A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity.

Indirubin-based compounds affect diverse biological processes, such as inflammation and angiogenesis. In this study, we tested a novel indirubin derivative, LDD-1819 (2-((((2Z,3E)-5-hydroxy-5'-nitro-2'-oxo-[2,3'-biindolinylidene]-3-ylidene)amino)oxy)ethan-1-aminium chloride) for two major biological activities: cell plasticity and anti-cancer activity. Biological assays indicated that LDD-1819 induced somatic cell plasticity. LDD-1819 potentiated myoblast reprogramming into osteogenic cells and fibroblast reprogramming into adipogenic cells. Interestingly, in an assay of skeletal muscle dedifferentiation, LDD-1819 induced human muscle cellularization and blocked residual proliferative activity to produce a population of mononuclear refractory cells, which is also observed in the early stages of limb regeneration in urodele amphibians. In cancer cell lines, LDD-1819 treatment inhibited cell invasion and selectively induced apoptosis compared to normal cells. In an animal tumor xenograft model, LDD-1819 reduced human cancer cell metastasis in vivo at doses that did not produce toxicity. Biochemical assays showed that LDD-1819 possessed inhibitory activity against glycogen synthase kinase-3ß, which is linked to cell plasticity, and aurora kinase, which regulates carcinogenesis. These results indicate that novel indirubin derivative LDD-1819 is a dual inhibitor of glycogen synthase kinase-3ß and aurora A kinase, and has potential for development as an anti-cancer drug or as a reprogramming agent for cell-therapy based approaches to treat degenerative diseases.

5-Nitro-5'hydroxy-indirubin-3'oxime is a novel inducer of somatic cell transdifferentiation.

Patient-derived cell transplantation is an attractive therapy for regenerative medicine. However, this requires effective strategies to reliably differentiate patient cells into clinically useful cell types. Herein, we report the discovery that 5-nitro-5'hydroxy-indirubin-3'oxime (5'-HNIO) is a novel inducer of cell transdifferentiation. 5'-HNIO induced muscle transdifferentiation into adipogenic and osteogenic cells. 5'-HNIO was shown to inhibit aurora kinase A, which is a known cell fate regulator. 5'-HNIO produced a favorable level of transdifferentiation compared to other aurora kinase inhibitors and induced transdifferentiation across cell lineage boundaries. Significantly, 5'-HNIO treatment produced direct transdifferentiation without up-regulating potentially oncogenic induced pluripotent stem cell (iPSC) reprogramming factors. Thus, our results demonstrate that 5'-HNIO is an attractive molecular tool for cell transdifferentiation and cell fate research.

Chemical targeting of GAPDH moonlighting function in cancer cells reveals its role in tubulin regulation.

Glycolytic enzymes are attractive anticancer targets. They also carry out numerous, nonglycolytic "moonlighting" functions in cells. In this study, we investigated the anticancer activity of the triazine small molecule, GAPDS, that targets the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDS showed greater toxicity against cancer cells compared to a known GAPDH enzyme inhibitor. GAPDS also selectively inhibited cell migration and invasion. Our analysis showed that GAPDS treatment reduced GAPDH levels in the cytoplasm, which would modulate the secondary, moonlighting functions of this enzyme. We then used GAPDS as a probe to demonstrate that a moonlighting function of GAPDH is tubulin regulation, which may explain its anti-invasive properties. We also observed that GAPDS has potent anticancer activity in vivo. Our study indicates that strategies to target the secondary functions of anticancer candidates may yield potent therapeutics and useful chemical probes.

Double-stranded DNA-graphene hybrid: preparation and anti-proliferative activity.

Herein, we demonstrate a simple method to prepare graphene dispersions in an aqueous solution of DNA by the sonication of bulk graphite. The use of a commercial double-stranded DNA as a stabilizer for graphite exfoliation without any chemical modification is presented. The high energy sound waves cleave a double-stranded DNA into two single-stranded DNAs. UV-vis spectral studies show that the nucleobases in the product are intact. Atomic force microscopy studies reveal that the size of the obtained nanosheets can be enriched into smaller lateral dimensions using centrifugation. Raman spectroscopy suggests that the defects found in the nanosheets induced by the sonication are edge defects, whereas the bodies of the sheets remain relatively defect free. The graphene dispersions are extremely stable over a wide range of pH values, possessing high negative zeta potential values. The anti-proliferative effect observed through in vitro cytotoxicity studies is supported by in vivo studies using the zebrafish human tumor xenograft model. The migration of cancer cells in zebrafish embryos are inhibited by the graphene nanosheet dispersion. The negatively charged nanosheet serves as a platform for the adsorption of gold nanoparticles with positively charged surfaces.