YZ9

Effect of ceramic infrastructure on the failure behavior and stress distribution of fixed partial dentures.[Pubmed:25657090]

Dent Mater. 2015 Apr;31(4):413-22.

OBJECTIVES: The effect of the ceramic infrastructure (IS) on the failure behavior and stress distribution of fixed partial dentures (FPDs) was evaluated. METHODS: Twenty FPDs with a connector cross-section of 16 mm(2) were produced for each IS and veneered with porcelain: (YZ) Vita In-Ceram YZ/Vita VM9 porcelain; (IZ) Vita In-Ceram Zirconia/Vita VM7 porcelain; (AL) Vita In-Ceram AL/Vita VM7 porcelain. Two experimental conditions were evaluated (n = 10). For control specimens, load was applied in the center of the pontic at 0.5 mm/min until failure, using a universal testing machine, in 37 degrees C deionized water. For mechanical cycling (MC) specimens, FPDs were subjected to MC (2 Hz, 140 N, 10(6) cycles) and subsequently tested as described for the control group. For YZ, an extra group of 10 FPDs were built with a connector cross-section of 9 mm(2) and tested until failure. Fractography and FEA were performed. Data were analyzed by ANOVA and Tukey's test (alpha = 0.05). RESULTS: YZ16 showed the greatest fracture load mean value, followed by YZ16-MC. Specimens from groups YZ9, IZ16, IZ16-MC, AL16 and AL16-MC showed no significant difference for the fracture load. SIGNIFICANCE: The failure behavior and stress distribution of FPDs was influenced by the type of IS. AL and IZ FPDs showed similar fracture load values but different failure modes and stress distribution. YZ showed the best mechanical behavior and may be considered the material of choice to produce posterior FPDs as it was possible to obtain a good mechanical performance even with a smaller connector dimension (9 mm(2)).

Structure-based development of small molecule PFKFB3 inhibitors: a framework for potential cancer therapeutic agents targeting the Warburg effect.[Pubmed:21957443]

PLoS One. 2011;6(9):e24179.

Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3*N4A complex to 2.4 A resolution and, exploiting the resulting molecular information, attained the more potent YN1. When tested on cultured cancer cells, both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in turn suppressed glycolysis and, ultimately, led to cell death. This study validates PFKFB3 as a target for new cancer therapies and provides a framework for future development efforts.