The introduction of induced pluripotent stem cells (iPSCs) has opened up the potential for personalized cell therapies and ushered in new opportunities for regenerative medicine, disease modeling, iPSC-based drug discovery and toxicity assessment. Over the past 10 years, several initiatives have been established that aim to collect and generate a large amount of human iPSCs for scientific research purposes. In this review, we compare the construction and operation strategy of some iPSC banks as well as their ongoing development. We also introduce the technical challenges and offer future perspectives pertaining to the establishment and management of iPSC banks.

The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.

Osteosarcoma is the most common primary solid tumor of bone. It has a high metastatic potential and occurs predominantly in adolescents and young adults. Angiopoietin 2 (Angpt2) is a key regulator in tumor angiogenesis, facilitating tumor growth and metastasis. Connective tissue growth factor (CTGF, also known as CCN2), is a cysteine-rich protein that has been reported to promote metastasis of osteosarcoma. However, the effect of CTGF on Angpt2 regulation and angiogenesis in human osteosarcoma remains largely unknown. We found that overexpression of CTGF in osteosarcoma cells increased Angpt2 production and induced angiogenesis, in vitro and in vivo. Our findings demonstrate that CTGF-enhanced Angpt2 expression and angiogenesis is mediated by the phospholipase C (PLC)/protein kinase C (PKCδ) signaling pathway. Moreover, endogenous microRNA-543 (miR-543) expression was negatively regulated by CTGF via the PLC/PKCδ pathway. We also provide evidence showing clinical significance between CTGF, Angpt2, and miR-543 as well as tumor staging in human osteosarcoma tissue. CTGF may serve as a therapeutic target in the process of osteosarcoma metastasis and angiogenesis.

Purpose: To clarify the effects of cyclin E1 suppression on antitumor efficacy of sorafenib in hepatocellular carcinoma cells and to explore the potential of combining sorafenib with cyclindependent kinase (CDK) inhibition in therapy.Experimental Design: The effects of cyclin E1 suppression on sorafenib-induced apoptosis were tested in both sorafenibsensitive (Huh-7 and HepG2, IC 50 5-6 mmol/L) and sorafenib-resistant (Huh-7R and HepG2R, IC 50 14-15 mmol/L) hepatocellular carcinoma cells. The activity of pertinent signaling pathways and the expression of cell cycle and apoptosisrelated proteins were measured using Western blotting. Efficacy of sorafenib combined with the pan-CDK inhibitor flavopiridol was tested both in vitro and in xenograft experiments. The pertinent downstream mediators of antitumor efficacy were tested in transient transfection and RNA interference experiments.Results: Cyclin E1 mRNA and protein expressions were suppressed after sorafenib treatment in sorafenib-sensitive but not in sorafenib-resistant hepatocellular carcinoma cells. Changes in cyclin E2 or D1 were not correlated with sorafenib sensitivity. The knockdown of cyclin E1 expression reversed the resistance of hepatocellular carcinoma cells to sorafenib in terms of cell growth and apoptosis induction, whereas the overexpression of cyclin E1 increased the resistance to sorafenib. The growth-inhibitory and apoptosis-inducing effects of sorafenib were enhanced by flavopiridol, and Mcl-1 suppression was determined to play a critical role in mediating this enhancing effect.Conclusions: The cyclin E1 suppression in hepatocellular carcinoma cells may serve as a pharmacodynamic biomarker for predicting sorafenib efficacy. The combination of sorafenib and CDK inhibitors may improve the efficacy of sorafenib in hepatocellular carcinoma.

B-cell translocation gene 3 (BTG3) is a member of the antiproliferative BTG/ Transducer of ErbB2 gene family and is induced by genotoxic stress in a p53-and Checkpoint kinase 1 (CHK1)-dependent manner. Down-regulation of BTG3 has been observed in human cancers, suggesting that it plays an important role in tumor suppression, although the underlying mechanisms are unclear. Here, we report that BTG3 interacts with CHK1, a key effector kinase in the cell cycle checkpoint response, and regulates its phosphorylation and activation. Upon interaction, BTG3 mediates K63-linked ubiquitination of CHK1 at Lys132 through the cullin-RING ligase 4Cdt2 E3 complex, thus facilitating CHK1 chromatin association. We show that BTG3-depleted cells phenocopy those CHK1-deficient cells, exhibiting increased cell death after replication block and impaired chromosome alignment and segregation. These defects could be corrected by wild-type BTG3 but not by a mutant impaired in CHK1 interaction. We propose that BTG3-dependent CHK1 ubiquitination contributes to its chromatin localization and activation and that a defect in this regulation may increase genome instability and promote tumorigenesis.