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Objectives: Melanoma is a highly aggressive and metastatic form of cancer, and the role of exosomal microRNAs (miRNAs) in its progression remains largely unexplored. This study aimed to investigate the effects of melanoma cell-derived exosomal miR-424-5p on angiogenesis and its underlying mechanisms. Methods: Exosomes were isolated from melanoma cell lines A375 and A2058, and their effects on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were examined. The interaction between miR-424-5p and its target gene, large tumor suppressor kinase 2 (LATS2), was analyzed using luciferase reporter assays and functional experiments. In vivo, tumor growth and angiogenesis were studied in a xenograft model using nude mice. Results: Melanoma cell-derived exosomes could be internalized by HUVECs, which promoted proliferation, migration, and angiogenesis. miR-424-5p was highly expressed in melanoma cells and their exosomes, and its inhibition in exosomes suppressed HUVEC proliferation, migration, and angiogenesis. LATS2 was identified as a direct target of miR-424-5p, and its silencing reversed the inhibitory effects of miR-424-5p inhibition on HUVEC functions. In vivo, exosomes derived from miR-424-5p-inhibited melanoma cells suppressed tumor growth and angiogenesis in xenograft models. Conclusions: Melanoma cell-derived exosomal miR-424-5p promotes angiogenesis by targeting LATS2, contributing to melanoma progression. Targeting the exosomal miR-424-5p/LATS2 axis could be a potential therapeutic strategy for melanoma. [ABSTRACT FROM AUTHOR]

Exosomes are extracellular vesicles that received attention for their potential use in the treatment of various injuries. They communicate intercellularly by transferring genetic and bioactive molecules from parent cells. Although exosomes hold immense promise for treating neurodegenerative and oncological diseases, their actual clinical use is very limited because of their biogenesis and secretion. Recent studies have shown that small molecules can significantly enhance exosome biogenesis, thereby remarkably improving yield, functionality, and therapeutic effects. These molecules modulate critical pathways toward optimum exosome production in a mode that is either ESCRT dependent or ESCRT independent. Improved exosome biogenesis may provide new avenues for targeted cancer therapy, neuroprotection in neurodegenerative diseases, and regenerative medicine in wound healing. This review explores the role of small molecules in enhancing exosome biogenesis and secretion, highlights their underlying mechanisms, and discusses emerging clinical applications. By addressing current challenges and focusing on translational opportunities, this study provides a foundation for advancing cell-free therapies in regenerative medicine and beyond., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neurocognitive disorders are characterized by a decline in various components of cognitive function, resulting in a high rate of morbidity and mortality. Despite multiple efforts, there is still a lack of practical preventive and therapeutic approaches for these diseases, and current pharmaceuticals have failed to manage their progression. Consequently, this chapter aims to provide a concise overview of the existing preclinical and clinical evidence that explores the impact of plant-based therapies on the prevention and treatment of neurocognitive disorders.We thoroughly searched different web databases to identify preclinical and clinical studies that investigate the effect of plant-based medicines on cognitive function in animal models, as well as individuals who are healthy, those with mild cognitive decline, or those with Alzheimer's disease. We included studies that examined plant extracts, multi-component herbal preparations, and phytochemicals such as Nigella sativa Linn., Rosmarinus officinalis L., Ginkgo biloba, and Melissa officinalis. The neuroprotective effects of these plants were associated with their anticholinesterase, anti-inflammatory, and antioxidative activities. None of the included studies reported severe adverse reactions.In conclusion, the results of the preclinical and clinical studies indicate the potential benefits of plant-based therapies on neurocognitive disorders. However, more extended and comprehensive clinical studies must confirm these findings thoroughly., (© 2025. The Author(s), under exclusive license to Springer Nature Switzerland AG.)