Muscadine grape skin extract inhibits prostate cancer cells by inducing cell-cycle arrest, and decreasing migration through heat shock protein 40.

Previously we demonstrated that muscadine grape skin extract (MSKE), a natural product, significantly inhibited androgen-responsive prostate cancer cell growth by inducing apoptosis through the targeting of survival pathways. However, the therapeutic effect of MSKE on more aggressive androgen-independent prostate cancer remains unknown. This study examined the effects of MSKE treatment in metastatic prostate cancer using complementary PC-3 cells and xenograft model. MSKE significantly inhibited PC-3 human prostate cancer cell tumor growth in vitro and in vivo. The growth-inhibitory effect of MSKE appeared to be through the induction of cell-cycle arrest. This induction was accompanied by a reduction in the protein expression of Hsp40 and cell-cycle regulation proteins, cyclin D1 and NF-kBp65. In addition, MSKE induced p21 expression independent of wild-type p53 induced protein expression. Moreover, we demonstrate that MSKE significantly inhibited cell migration in PC-3 prostate cancer cells. Overall, these results demonstrate that MSKE inhibits prostate tumor growth and migration, and induces cell-cycle arrest by targeting Hsp40 and proteins involved in cell-cycle regulation and proliferation. This suggests that MSKE may also be explored either as a neo-adjuvant or therapeutic for castration resistant prostate cancer.

Simulating the slow to fast switch in cytochrome c oxidase catalysis by introducing a loop flip near the enzyme's cytochrome c (substrate) binding site.

The mitochondrial enzyme cytochrome c oxidase catalyzes the reduction of molecular oxygen in the critical step of oxidative phosphorylation that links the oxidation of food consumed to ATP production in cells. The enzyme catalyzes the reduction of oxygen at two vastly different rates that are thought to be linked to two different conformations but the conformation of the "fast enzyme" remains obscure. In this study, we demonstrated how oxygen binding at haem a3 could trigger long-distance conformational changes and then simulated a conformational change in an eight-residue loop near the enzyme's substrate (cytochrome c) binding site. We then used this modified cytochrome c oxidase (COX) to simulate a stable COX-cytochrome c enzyme-substrate (ES) complex. Compared to ES complexes formed in the absence of the conformation change, the distance between the redox centers of the two proteins was reduced by half and instead of nine, only four COX amino acid residues were found along the axis linking the electron entry point and the CuA redox center of COX: We proposed that intramolecular electron transfer in COX occurs via a charge/hydrogen relay system involving these four residues. We suggest that the conformational change and resulting shortened electron pathway are features of fast-acting COX.

Stakeholder perspectives on outcome expectations of pharmacy graduates from a Caribbean school of pharmacy.

OBJECTIVES: To explore stakeholders' views regarding the performance of pharmacy graduates upon entering the workforce and to identify curricular deficiencies and possible solutions. METHODS: Practicing pharmacists, many of whom were members of government and pharmacy organizations, were asked to complete a 40-item questionnaire to determine their views regarding the educational outcomes of pharmacy graduates from a Caribbean pharmacy school. In addition, the stakeholders participated in focus group discussions to capture feedback not gathered on the questionnaire. RESULTS: Ten stakeholders completed the questionnaire and 11 participated in the focus group discussions. Stakeholders rated graduates higher than average in 13 educational outcomes: application of knowledge and skills, patient care, communication skills, confidentiality, ethics, problem solving, and innovation. However, responses to open-ended questions and comments made during the focus group discussions identified deficiencies, which included a lack of clinical faculty members and qualified preceptors to teach pharmacy students, and the need to revise basic sciences courses. CONCLUSION: Feedback from key stakeholders suggests that the quality of pharmacy graduates is above average for the most part; however, additional work is needed to address the deficiencies identified.