Generation of rat-derived lung epithelial cells in Fgfr2b-deficient mice retains species-specific development.

Regenerative medicine is a tool to compensate for the shortage of lungs for transplantation, but it remains difficult to construct a lung in vitro due to the complex three-dimensional structures and multiple cell types required. A blastocyst complementation method using interspecies chimeric animals has been attracting attention as a way to create complex organs in animals, although successful lung formation using interspecies chimeric animals has not yet been achieved. Here, we applied a reverse-blastocyst complementation method to clarify the conditions required to form lungs in an Fgfr2b-deficient mouse model. We then successfully formed a rat-derived lung in the mouse model by applying a tetraploid-based organ-complementation method. Importantly, rat lung epithelial cells retained their developmental timing even in the mouse body. These findings provide useful insights to overcome the barrier of species-specific developmental timing to generate functional lungs in interspecies chimeras.

ARID2 is a pomalidomide-dependent CRL4CRBN substrate in multiple myeloma cells.

The immunomodulatory drug (IMiD) thalidomide and its derivatives lenalidomide and pomalidomide are therapeutic agents used in the treatment of multiple myeloma. Although pomalidomide offers considerable clinical benefits to patients with lenalidomide-resistant multiple myeloma, the molecular mechanisms underlying its superior efficacy remain unclear. Here we show that ARID2, a component of the polybromo-associated BAF (PBAF) chromatin-remodeling complex, is a pomalidomide-induced neosubstrate of CRL4CRBN. BRD7, another subunit of PBAF, is critical for pomalidomide-induced ARID2 degradation. ARID2 is involved in transcriptional regulation of pomalidomide target genes including MYC. Pomalidomide is more effective than lenalidomide in degrading ARID2 and is capable of inhibiting MYC expression and proliferation in lenalidomide-resistant cell lines. Notably, ARID2 expression is associated with a poor prognosis and is higher in chemoresistant minimal residual disease (MRD) populations, and in patients with relapsed/refractory multiple myeloma. These findings suggest that ARID2 is a promising target for overcoming lenalidomide resistance in patients with multiple myeloma.

Color changes in bulk-fill resin composites as a result of visible light-curing.

We evaluated twelve commercially available bulk-fill resin composites to determine the colorimetric changes that occurred as a result of the photo-polymerization reaction. Samples of the resin composites were prepared as disks 8 mm in diameter and 3 mm in thickness. A colorimeter was used to measure the color of samples on a black background before and after the polymerization processed had been initiated. As results, each of the photo-initiated bulk-fill resin composites tested except for Beautifil Bulk A showed a significant color difference more than that of conventional resin composites. Bulk Base Flow became darker, whereas Beautifil Bulk Flow became clearly lighter. All resin composites except for Bulk Base Flow became less yellow. Thus, Beautifil Bulk A exhibited the least color change among all the bulk-fill resin composites. However, this color change showed a marked change (NBS units) as observed by the human naked eye.

Use of new scratch test and tensile test for evaluation of bond strength of selfadhesive flowable resin composite for repair of artificial tooth erosion.

The purpose of this study was to use a new scratch test and tensile test to evaluate the bond strength between artificial erosive enamel or dentin and self-adhesive resin composites as a coating material. Coronal enamel or dentin surface was exposed to an erosive cycle (artificial saliva [AS], pH:7.0 for 6.5 h and acidic carbonated beverages for 5 min, alternated 3 times per day) for the eroded-surface or stored in AS for the remineralized-surface. Two self-adhesive flowable resin composites, Fusio and LLB-CR6 (prototype), and a conventional flowable resin composite, BEAUTIFIL FLOW with self-etching primer system, Clearfil Mega Bond, were applied to enamel or dentin surfaces; and then the bond strengths were measured. For the eroded-surface, there were no significant differences in bonding strength among all materials, as assessed by the new scratch test. Thus, these self-adhesive flowable resin composites might be useful for coating materials on acid-eroded tooth surfaces.

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex.

Restores TBP function 1 (Rtf1) is generally considered to be a subunit of the Paf1 complex (PAF1C), a multifunctional protein complex involved in histone modification and transcriptional or posttranscriptional regulation. Rtf1, however, is not stably associated with the PAF1C in most species except Saccharomyces cerevisiae, and its biochemical functions are not well understood. Here, we show that human Rtf1 is a transcription elongation factor that may function independently of the PAF1C. Rtf1 requires "Rtf1 coactivator" activity, which is most likely unrelated to the PAF1C or DSIF, for transcriptional activation in vitro. A mutational study revealed that the Plus3 domain of human Rtf1 is critical for its coactivator-dependent function. Transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation studies in HeLa cells showed that Rtf1 and the PAF1C play distinct roles in regulating the expression of a subset of genes. Moreover, contrary to the finding in S. cerevisiae, the PAF1C was apparently recruited to the genes examined in an Rtf1-independent manner. The present study establishes a role for human Rtf1 as a transcription elongation factor and highlights the similarities and differences between the S. cerevisiae and human Rtf1 proteins.

A novel DDS strategy, "dual-targeting", and its application for antineovascular therapy.

Dual-targeting liposomes modified with Ala-Pro-Arg-Pro-Gly (APRPG) and Gly-Asn-Gly-Arg-Gly (GNGRG) peptides were developed. They remarkably associated to growing human umbilical vein endothelial cells (HUVECs) compared with single-targeting liposomes modified with APRPG or GNGRG. Doxorubicin (DOX) encapsulated in the dual-targeting liposomes significantly suppressed the growth of HUVECs compared with that in single-targeting liposomes. The dual-targeting liposomes containing DOX strongly suppressed tumor growth in Colon26 NL-17 carcinoma-bearing mice. Confocal microscopic data indicated that this anticancer effect was brought by the association of these liposomes to angiogenic vessels in the tumor. These findings suggest that "dual-targeting" would be a hopeful method for targeting therapies.