Regulation of Hepatocyte Nuclear Factor 4α Attenuated Lipotoxicity but Increased Bile Acid Toxicity in Non-Alcoholic Fatty Liver Disease

Hepatocyte nuclear factor 4 alpha (HNF4α) is a key master transcriptional factor for hepatic fat and bile acid metabolic pathways. We aimed to investigate the role of HNF4α in non-alcoholic fatty liver disease (NAFLD). The role of HNF4α was evaluated in free fatty acid–induced lipotoxicity and chenodeoxycholic acid (CDCA)-induced bile acid toxicity. Furthermore, the role of HNF4α was evaluated in a methionine choline deficiency (MCD)-diet-induced NAFLD model. The overexpression of HNF4α reduced intracellular lipid contents and attenuated palmitic acid (PA)-induced lipotoxicity. However, the protective effects of HNF4α were reversed when CDCA was used in a co-treatment with PA. HNF4α knockdown recovered cell death from bile acid toxicity. The inhibition of HNF4α decreased intrahepatic inflammation and the NAFLD activity score in the MCD model. Hepatic HNF4α inhibition can attenuate bile acid toxicity and be more effective as a therapeutic strategy in NAFLD patients; however, it is necessary to study the optimal timing of HNF4α inhibition

Ligand Coupling and Decoupling Modulates Stem Cell Fate

In natural microenvironment, various proteins containing adhesive ligands in fibrous and non-fibrous structures dynamically couple and decouple to regulate stem cell fate. Herein, materials presenting movably couplable ligands are developed by grafting liganded gold nanoparticles (AuNPs) to a substrate followed by flexibly grafting liganded movable linear nanomaterials (MLNs) to the substrate via a long bendable linker, thereby creating a space between the MLNs and the AuNPs in the decoupled state. Magnetic control of the MLNs decreases this space via the bending of the linker to couple the MLNs to the AuNPs. Remote control of ligand coupling stimulates integrin recruitment to the coupled ligands, thereby non-toxically facilitating the focal adhesion, mechanosensing, and potential differentiation of stem cells, which is suppressed by ligand decoupling. Versatile tuning of size, aspect ratio, distributions, and ligands of the MLNs can help to decipher dynamic ligand-coupling-dependent stem cell fate to advance regenerative therapies.11Nsciescopu

Mass propagation of microtubers from suspension cultures of Pinellia ternata cells and quantitative analysis of succinic acid in Pinellia tubers

The conditions for efficient tuber production from suspension cultures of Pinellia ternata cells which is one of medicinal herbs were established and succinic acid in tubers propagated in vitro was determined. Leaf explants formed white nodular structures and off-white calluses at a frequency of 90.6 % when cultured on Murashige and Skoog medium supplemented with 0.54 μM α-naphthaleneacetic acid (NAA); however, this frequency declined substantially with increasing NAA concentration, up to 16.2 μM, at which the frequency reached zero percent. In combination treatments with 4.44 μM 6-benzyladenine (BA) and NAA, however, the frequency of white nodular structure and off-white callus formation from leaf explants did not decrease, even at 16.2 μM NAA. Suspension cultures of P. ternata cells were established from leaf-derived off-white calluses in MS liquid medium containing 5.4 μM NAA and 4.44 μM BA. Upon plating onto MS basal medium, over 90 % of cell aggregates gave rise to microtubers and developed into plantlets. Regenerated plantlets were transplanted in potting soil and grown to maturity in a growth chamber, with a survival rate of >90 %. The highest succinic acid content in suspension culture-derived microtubers was 45 g/kg of extract. Compared with wild P. ternata medicinal tubers, the succinic acid content was very similar. The in vitro P. ternata microtuber proliferation system established in this study is thus an efficient alternative for the mass production of medicinal tubers. © 2015, Korean Society for Plant Biotechnology and Springer Japan.

Modulation of Macrophages by In Situ Ligand Bridging

Extracellular matrix (ECM) proteins containing cell-attachable Arg-Gly-Asp (RGD) sequences exhibit variable bridging and non-bridging in fibronectin-collagen and laminin-collagen complexes that can regulate inflammation, tissue repair, and wound healing. In this study, linking molecule-mediated conjugation of 1D magnetic nanocylinders (MNCs) to material surfaces pre-decorated with gold nanospheres (GNSs) is performed, thereby yielding RGD-coated MNCs (RGD-MNCs) over RGD-coated GNSs (RGD-GNSs) in a non-bridging state. The RGD-MNCs are drawn closer to the RGD-GNSs via magnetic field-mediated compression of the linking molecules to establish the bridging between them. Relative proportion of the RGD-MNCs to the RGD-GNSs is optimized to yield effective remote stimulation of integrin binding to variably bridged RGDs similar to that of invariably bridged RGDs used as a control group. Remote manipulation of the RGD bridging facilitates the attachment structure assembly of macrophages that leads to pro-healing/anti-inflammatory phenotype acquisition. In contrast, the non-bridged RGDs inhibited macrophage attachment that acquired pro-inflammatory phenotypes. The use of various nanomaterials in constructing heterogeneous RGD-coated materials can further offer various modes in remote switching of RGD bridging and non-bridging to understand dynamic integrin-mediated modulation of macrophages that regulate immunomodulatory responses, such as foreign body responses, tissue repair, and wound healing