Exosomes are nanoscale, membrane-bound vesicles secreted by various cell types. Owing to their cargo of parental cel-derived cellular components, exosomes show significant promise as clinical biomarkers. Meanwhile, due to their diverse origins and cargo, exosomes play a dual role in cancer, possessing the capacity to both promote and suppress tumor progression The efficient and rapid isolation and purification of exosomes are foundational for advancing their clinical applications. Additionally, a comprehensive understanding of exosome biogenesis is essential to elucidate their underlying biological functions. However, current knowledge regarding their biological characteristics and functions of action remains limited. This review delves into exosome isolation techniques, the regulatory mechanisms underlying their biogenesis and secretion, and their dual roles in cancer progression, metastasis, and tumor immunity, concluding with a discussion of the challenges and future directions in their clinical translation.
Ying-Ying Li, Ya Gao, Yanhong Wang et al.· Frontiers in Cell and Develo...· 0 citations
Nine previously undescribed prenylated xanthones, aspxanthones A-I (1-9), were isolated and characterized from the endophytic fungus Aspergillus sp. TJ507. Their structures were established through comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and DP4+ probability analysis. Compounds 1, 2, and 4 exhibited modest in vitro SIRT1 activating effects, with EC50 values ranging from 9.3 to 13.7 μM. The positive control resveratrol yielded an EC50 of 2.4 ± 0.4 μM under identical assay conditions. Molecular docking was conducted with resveratrol as a reference ligand, which revealed obvious differences in binding modes between resveratrol and the tested xanthones. To further clarify their dynamic binding behaviors, molecular dynamics simulations, free-energy landscape analysis, and MM/GBSA calculations were carried out on these active compounds. Among them, compound 4 displayed the most stable simulated binding profile and the most favorable estimated binding free energy among the three complexes, broadly consistent with the experimental activity ranking. In contrast, compound 2 exhibited higher conformational flexibility throughout the simulation, indicating a distinct binding mode. This study expands the chemical diversity of fungal-derived xanthones and provides valuable templates for the design and development of potential SIRT1 activators.
Xueqi Lan, Dong-Chun Liang, Li Tang et al.· Bioorganic chemistry (Print)· 0 citations
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