Cadherin-6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell-derived factor-1.

Glioblastoma recruits various nontransformed cells from distant tissues. Although bone marrow-derived mesenchymal stem cells (MSCs) have been observed migrating to glioblastoma, the underlying mechanism driving MSC migration toward glioblastoma remains unclear. Tumor vascularity is critical in the context of recurrent glioblastoma and is closely linked to the expression of stromal cell-derived factor-1 (SDF-1). We demonstrated that cadherin-6 mediated MSC migration both toward SDF-1 and toward glioblastoma cells. Cadherin-6 knockdown resulted in the downregulation of MSCs capacity to migrate in response to SDF-1. Furthermore, MSCs with cadherin-6 knockdown exhibited impaired migration in response to conditioned media derived from glioblastoma cell lines (U87 and U373) expressing SDF-1, thus simulating the glioblastoma microenvironment. Moreover, MSCs enhanced the vasculogenic capacity of U87 cells without increasing the proliferation, cancer stem cell characteristics, or migration of U87. These results suggest that the current strategy of utilizing MSCs as carriers for antiglioblastoma drugs requires careful examination. Furthermore, cadherin-6 may represent a novel potential target for controlling the recruitment of MSCs toward glioblastoma.

Design, synthesis of new 3H-imidazo[4,5-b]pyridine derivatives and evaluation of their inhibitory properties as mixed lineage kinase 3 inhibitors.

Mixed-lineage protein kinase 3 (MLK3) is implicated in several human cancers and neurodegenerative diseases. A series of 3H-imidazo[4,5-b]pyridine derivatives were designed, synthesized and evaluated as novel MLK3 inhibitors. A homology model of MLK3 was developed and all designed compounds were docked to assess their binding pattern and affinity toward the MLK3 active site. Based on this knowledge, we synthesized and experimentally evaluated the designed compounds. Majority of the compounds showed significant inhibition of MLK3 in the enzymatic assay. In particular, compounds 9a, 9e, 9j, 9 k, 12b and 12d exhibited IC50 values of 6, 6, 8, 11, 14 and 14 nM, respectively. Furthermore, compounds 9a, 9e, 9 k and 12b exhibited favorable physicochemical properties among these compounds.

Molecular Oriented Charge Accumulation in High-Efficiency Polymer Solar Cells as Revealed by Operando Spin Analysis.

A low band-gap polymer, PTB7-Th, is one of the typical p-type semiconductors among the next-generation solar-cell materials that have achieved power conversion efficiencies of over 10%. However, the internal deterioration mechanism of high-efficiency polymer solar cells such as PTB7-Th-based cells is still an open issue and has been extensively studied. Here, we report a study with operando electron spin resonance (ESR) spectroscopy for PTB7-Th polymer solar cells with an n-type semiconductor PC71BM to clarify the internal deterioration mechanism at a molecular level. We have directly observed ambipolar charge accumulation with a face-on molecular orientation in the cells under simulated solar irradiation using an operando light-induced ESR technique. Moreover, we have found a clear correlation between the charge accumulation and performance deterioration of the cells. The charge accumulation sites have been clarified by the ESR analysis and density functional theory calculation. The prevention of such charge accumulation on the basis of the present finding would be important for the commercialization of high-efficiency polymer solar cells.

Protective efficacy and immunogenicity of an inactivated avian-origin H3N2 canine influenza vaccine in dogs challenged with the virulent virus.

Transmission of avian-origin influenza A virus (H3N2) to dogs had been reported and since then the H3N2 virus infection across South Korea has been occurred repeatedly in the country's animal clinics and kennels. Dog-to-dog transmission of the virus had also been experimentally demonstrated by direct contact. In this study, immunogenicity and protective efficacy against challenge exposure of the formalin-inactivated H3N2 influenza virus vaccine with a synthetic polymer adjuvant was investigated in dogs. The beagle puppies received two inactivated vaccine injections intramuscularly 2 weeks apart. Serological investigation by a hemagglutination inhibition (HI) test and an ELISA assay indicated that a significant increase in antibody titer was displayed 2 weeks after the second vaccination. Clinical signs, virus shedding and histopathological lesions in the lungs were exhibited in unvaccinated beagle puppies directly challenged through an intranasal route with the virus 2 weeks after the second vaccination. However, the vaccinated animals did not show any clinical signs and showed milder pathological lung lesions and shorter shedding duration with lower loads than controls'. These results indicated that the synthetic polymer-adjuvant avian-origin canine influenza virus (CIV) vaccine had produced antibody response and protection from avian-origin CIV challenge in dogs.