Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay.

i-Motifs are quadruplex DNA structures formed from sequences rich in cytosine and held together by intercalated, hemi-protonated cytosine-cytosine base pairs. These sequences are prevalent in gene promoter regions and may play a role in gene transcription. Targeting these structures with ligands could provide a novel way to target genetic disease but there are very few ligands which have been shown to interact with i-motif DNA. Fluorescent intercalator displacement (FID) assays are a simple way to screen ligands against DNA secondary structures. Here we characterise how thiazole orange interacts with i-motif DNA and assess its ability for use in a FID assay. Additionally, we report FID-based ligand screening using thiazole orange against the i-motif forming sequence from the human telomere to reveal new i-motif binding compounds which have the potential for further development.

Adipose-Derived Mesenchymal Stem Cells and Their Derived Epidermal Progenitor Cells Conditioned Media Ameliorate Skin Aging in Rats.

BACKGROUND: Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging. METHODS: In this study, we isolated and characterized adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of male Sprague Dawley rats. We assessed the in vitro differentiation of Ad-MSCs into epidermal progenitor cells (EPCs) using ascorbic acid and hydrocoritsone. Additionally, we induced skin aging in female Sprague Dawley rats via daily intradermal injection of D-galactose over a period of 8 weeks. Then we evaluated the therapeutic potential of intradermal transplantation of Ad-MSCs and conditioned media (CM) derived from differentiated EPCs in the D-galactose-induced aging rats. Morphological assessments, antioxidant assays, and histopathological examinations were performed to investigate the effects of the treatments. RESULTS: Our findings revealed the significant capability of Ad-MSCs to differentiate into EPCs. Notably, compared to the group that received CM treatment, the Ad-MSCs-treated group exhibited a marked improvement in morphological appearance, antioxidant levels and histological features. CONCLUSIONS: These results underscore the effectiveness of Ad-MSCs in restoring skin aging as a potential therapy for skin aging.