14-3-3 and Smad2/3 are crucial mediators of atypical-PKCs: Implications for neuroblastoma progression.

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and BE(2)-M17 cells: a PKC-ι-specific 5-amino-1-2,3-dihydroxy-4-(methylcyclopentyl)-1H-imidazole-4-carboxamide and a PKC-ζ specific 8-hydroxy-1,3,6-naphthalenetrisulfonic acid. Both compounds induced apoptosis and retarded the epithelial-mesenchymal transition (EMT) of NB cells. Proteins 14-3-3 and Smad2/3 acted as central regulators of aPKC-driven progression in BE(2)-C and BE(2)-M17 cells in relation to the Akt1/NF-κB and TGF-ß pathways. Data indicates that aPKCs upregulate Akt1/NF-κB and TGF-ß pathways in NB cells through an association with 14-3-3 and Smad2/3 that can be diminished by aPKC inhibitors. In summary, both inhibitors appear to be promising potential neuroblastoma therapeutics and merit further research.

Thermal behavior of resistant starches RS 2, RS 3, and RS 4.

The thermal behaviors of 3 resistant starch types-RS 2, RS 3, and RS 4-were investigated. Samples were heated in excess water to specific temperatures, from 35 to 85 degrees C at 5 degrees C intervals, and freeze-dried. The treated samples were analyzed using SEM, DSC, XRD, and HPSEC to determine the structural changes at granular and molecular levels. Light microscopy was used to determine real-time thermal behavior of the starches. Although the resistant starches did not show significant morphological changes, as revealed by microscopy, they underwent internal structural changes at low temperatures before complete phase transitions occurred. The structural changes were less in RS 2 compared to the other 2 starches studied. The nongranular material of RS 3's crystallinity decreased gradually from 35 to 85 degrees C and showed microscopically visible changes at >80 degrees C. Cross-linking might have prevented RS 4 from becoming completely amorphous within the temperature range (35 to 85 degrees C) tested. The study indicated that the extent of structural changes depended on the treatment temperature and RS type.