ABSTRACT
Biologically speaking, normal aging is a spontaneous and inevitable process of organisms over time. It is a complex natural phenomenon that manifests itself in the form of degenerative changes in structures and the decline of functions, with diminished adaptability and resistance. Brain aging is one of the most critical biological processes that affect the physiological balance between health and disease. Age-related brain dysfunction is a severe health problem that contributes to the current aging society, and so far, there is no good way to slow down aging. Mesenchymal stem cells (MSCs) have inflammation-inhibiting and proliferation-promoting functions. At the same time, their secreted exosomes inherit the regulatory and therapeutic procedures of MSCs with small diameters, allowing high-dose injections and improved therapeutic efficiency. This manuscript describes how MSCs and their derived exosomes promote brain neurogenesis and thereby delay aging by improving brain inflammation.
ABSTRACT
Accumulating evidence indicates that hepatocellular carcinoma (HCC) tumorigenesis, recurrence, metastasis, and therapeutic resistance are strongly associated with liver cancer stem cells (CSCs), a rare subpopulation of highly tumorigenic cells with self-renewal capacity and differentiation potential. Previous studies identified B cell leukemia/lymphoma-11b (BCL11B) as a novel tumor suppressor with impressive capacity to restrain CSC traits. However, the implications of BCL11B in HCC remain unclear. In this study, we found that low BCL11B expression was an independent indicator for shorter overall survival (OS) and time to recurrence (TTR) for HCC patients with surgical resection. In vitro and in vivo experiments confirmed BCL11B as a tumor suppressor in HCC with inhibitory effects on proliferation, cell cycle progression, apoptosis, and mobility. Furthermore, BCL11B could suppress CSC traits, as evidenced by dramatically decreased tumor spheroid formation, self-renewal potential and drug resistance. A Cignal Finder Array and dual-luciferase activity reporter assays revealed that BCL11B could activate the transcription of P73 via an E2F1-dependent manner. Thus, we concluded that BCL11B is a strong suppressor of retaining CSC traits in HCC. Ectopic expression of BCL11B might be a promising strategy for anti-HCC treatment with the potential to cure HBV-related HCC regardless of P53 mutation status.