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Zhou J.-N.,Beijing Institute of Transfusion Medicine | Zhou J.-N.,South China Research Center for Stem Cell and Regenerative Medicine | Zeng Q.,Beijing Institute of Transfusion Medicine | Zeng Q.,South China Research Center for Stem Cell and Regenerative Medicine | And 31 more authors.
Hepatology | Year: 2015

Emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor-related miRNAs were significantly decreased. Among these miRNAs, miR-125b expression was most strongly suppressed. We also found down-regulation of miR-125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR-125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR-125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR-125b attenuated EMT-associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR-125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR-125b suppressed EMT and EMT-associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR-125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR-125b for liver cancer. Conclusion: miR-125b exerts inhibitory effects on EMT and EMT-associated traits in HCC by SMAD2 and 4. Ectopic expression of miR-125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801-815). © 2015 by the American Association for the Study of Liver Diseases.

Zhai J.-L.,Guangxi Medical University | Zhai J.-L.,Beijing Institute of Transfusion Medicine | Cao N.,Beijing Institute of Transfusion Medicine | Yue W.,Beijing Institute of Transfusion Medicine | And 6 more authors.
Progress in Biochemistry and Biophysics | Year: 2016

Alzheimer's disease (AD) is currently an incurable neurodegenerative disease, which is the most common cause of dementia worldwide. AD is also a progressive disorder, pathologically characterized by extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments of microtubule-associated tau protein that is hyperphosphorylated and the density of tau tangles correlates well with regional and global aspects of AD-associated cognitive dysfunction. Furthermore, the established toxic role of tau in certain genetic forms of frontotemporal dementia strongly suggests that tau aggregation may result in a toxic gain-of-function leading to the AD-associated neurodegeneration. Thus, there is a growing interest in discovering novel compounds that will help in reducing the deleterious accumulation of tau protein tangles in the AD brain. Stem cells treatment open a gate to this which many drugs show hard to control the disease progression or enhance the patients' consideration function. hUC-MSCs (mesenchymal stem cells isolated from human Wharton's jelly of unbilical cord), emphasized by its powerful paracrine, great function of multi-directional differentiation and east to isolate, have been confirmed effective to many nervous system disease including AD. But the treatment mechanism was still unknown. Along with the studies of secreted factors by hUC-MSCs, the paracrine function of the adult stem cells attracted us to answer this treatment mechanism from those star factors. Here, we set up the AD model in vitro by okadaic acid (OA), and demonstrate that IL-6 maybe the key protein to effect the recovery function of hUC-MSCs to protect the injured cells.

Xie X.Y.,Beijing Institute of Transfusion Medicine | Xie X.Y.,South China Research Center for Stem Cell and Regenerative Medicine | Li Y.H.,Beijing Institute of Transfusion Medicine | Li Y.H.,South China Research Center for Stem Cell and Regenerative Medicine | And 2 more authors.
Science China Life Sciences | Year: 2014

The generation of red blood cells (RBCs) from stem cells provides a solution for deficiencies in blood transfusion. Currently, primary hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells have shown the potential to produce fully mature RBCs. Here, we discuss the advantages, induction protocols, progress and possible clinical applications of stem cells in RBC production. © 2014 The Author(s).

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