Effect of Crystallization on Shape Memory Effect of Poly(lactic Acid).

The opportunity for the preparation of high-performance shape memory materials was brought about by the excellent mechanical properties of poly(lactic acid) (PLA). As the effect of crystallization on shape memory was still unclear, this brings constraints to the high-performance design of PLA. The PLA plates with different aggregation structure were prepared by three kinds of molding methods in this paper. The PLA plates were pre-stretched with a series of different strains above glass transition temperature (i.e., 70 °C). The recovery stress and ratio of the material were measured above stretching temperature (i.e., 80 °C). Prolonging of annealing time resulted in more perfect crystal structure and higher crystallinity. The crystal region acted as network nodes in shape memory PLA, and crystal region structure determined the shape memory performance. Based on the experimental results, the structural evolution of network nodes in shape memory PLA was established.

HFE promotes mitotic cell division through recruitment of cytokinetic abscission machinery in hepatocellular carcinoma.

HFE (Hemochromatosis) is a conventional iron level regulator and its loss of function due to gene mutations increases the risk of cancers including hepatocellular carcinoma (HCC). Likewise, studies focusing on HFE overexpression in cancers are all limited to linking up these events as a consequence of iron level deregulation. No study has explored any iron unrelated role of HFE in cancers. Here, we first reported HFE as an oncogene in HCC and its undescribed function on promoting abscission in cytokinesis during mitotic cell division, independent of its iron-regulating ability. Clinical analyses revealed HFE upregulation in tumors linking to large tumor size and poor prognosis. Functionally and mechanistically, HFE promoted cytokinetic abscission via facilitating ESCRT abscission machinery recruitment to the abscission site through signaling a novel HFE/ALK3/Smads/LIF/Hippo/YAP/YY1/KIF13A axis. Pharmacological blockage of HFE signaling axis impeded tumor phenotypes in vitro and in vivo. Our data on HFE-driven HCC unveiled a new mechanism utilized by cancer cells to propel rapid cell division. This study also laid the groundwork for tumor intolerable therapeutics development given the high cytokinetic dependency of cancer cells and their vulnerability to cytokinetic blockage.

Involvement of gap junctions in propylthiouracil-induced cytotoxicity in BRL-3A cells.

Gap junctions (GJs), which are important plasma membrane channels for the transfer of signaling molecules between adjacent cells, have been implicated in drug-induced liver injury. However, the influence and the underlying mechanisms of GJs in propylthiouracil (PTU)-induced hepatotoxicity are unclear. In the present study, distinct manipulations were performed to regulate GJ function in the BRL-3A rat liver cell line. The results indicated that the toxic effect of PTU in BRL-3A cells was mediated by GJ intercellular communication, as cell death was significantly attenuated in the absence of functional GJ channels. Furthermore, the specific knockdown of connexin-32 (Cx32; a major GJ component protein in hepatocytes) using small interfering RNA was observed to decrease necrosis, intracellular PTU content and the level of reactive oxygen species (ROS) following PTU exposure. These observations demonstrated that suppressing GJ Cx32 could confer protection against PTU-induced cytotoxicity through decreasing the accumulation of PTU and ROS. To the best of our knowledge, the present study is the first to demonstrate the role and possible underlying mechanisms of GJs in the regulation of PTU-induced toxicity in BRL-3A rat liver cells.

Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes.

The effect of gap junction intercellular communication (GJIC) on docetaxel-induced hepatotoxicity and its underlying mechanisms are largely unknown. The present study involved investigating the effect of downregulating GJs derived from connexin (Cx) 32 in BRL-3A cells by three different mechanisms: Using a low-density culture; suppression of Cx32 using small interfering RNA; and use of the chemical inhibitor 2­aminoethoxydiphenyl borate (2­APB), all of which led to attenuated docetaxel hepatotoxicity. In order to investigate the relevant mechanisms involved, apoptosis and caspase activities of BRL­3A cells were determined. The increase of apoptosis and the activation of caspase­3 and caspase­9, but not caspase-8, were detected following cell exposure with docetaxel, demonstrating that the mitochondrial­mediated apoptosis pathway is largely responsible for docetaxel hepatotoxicity. However, reduced apoptosis and caspase­3, and ­9 activities were observed following docetaxel application when BRL­3A GJIC was deficient from the knockdown of Cx32 expression or pretreatment with 2­APB. These observations illustrate that GJs are important in docetaxel-induced hepatotoxicity. Furthermore, inhibition of GJIC could prevent amplification of toxicity to docetaxel. Due to GJIC blockage, this hepatoprotection was associated, in part, with decreasing apoptosis of BRL­3A cells through the mitochondrial pathway. The present study provides evidence for potential therapeutic targets for the treatment of docetaxel-induced liver injury.