Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid ß plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation.

In this study, polyhydroxyisoflavones that directly prevent the aggregation of both amyloid ß (Aß) and tau were expediently synthesized via divergent Pd(0)-catalyzed Suzuki-Miyaura coupling and then biologically evaluated. By preliminary structure-activity relationship studies using thioflavin T (ThT) assays, an ortho-catechol containing isoflavone scaffold was proven to be crucial for preventing both Aß aggregation and tau-mediated neurofibrillary tangle formation. Additional TEM experiment confirmed that ortho-catechol containing isoflavone 4d significantly prevented the aggregation of both Aß and tau. To investigate the mode of action (MOA) of 4d, which possesses an ortho-catechol moiety, 1H-15N HSQC NMR analysis was thoroughly performed and the result indicated that 4d could directly inhibit both the formation of Aß42 fibrils and the formation of tau-derived neurofibrils, probably through the catechol-mediated nucleation of tau. Finally, 4d was demonstrated to alleviate cognitive impairment and pathologies related to Alzheimer's disease in a 5XFAD transgenic mouse model.

Immobilization of Collagen on the Surface of a PEEK Implant with Monolayer Nanopores.

Polyetheretherketone (PEEK) is the only polymer material that can replace titanium implants in the field of orthopedics. This is because the mechanical properties of PEEK are similar to those of bone, and PEEK has natural radiolucency, chemical stability, and sterilization resistance. Despite these advantages, PEEK has a disadvantage-that it is bio-inert. Therefore, many studies have attempted to change the bio-inertness of PEEK into bioactivity. Among them, a method of forming pores by acid treatment is attracting attention. In this study, an attempt was made to form pores on the surface of PEEK implant using a mixed acid of sulfuric acid and nitric acid. As a result, it was found that the condition when the PEEK surface is in contact with the acid is very important. That is, it was possible to form single-layered nanopores on the surface by contacting PEEK with a mixed acid under ultrasound. Additionally, by immobilizing type I collagen on the porous PEEK surface through dopamine coating, it was possible to obtain collagen-immobilized porous PEEK (P-PEEK-Col) with high compatibility with osteoblasts. This P-PEEK-Col has high potential for use as a bone substitute that promotes bone formation.