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Nontoxic natural products useful in skin care cosmetics are of considerable interest. Tyrosinase is a rate-limiting enzyme for which its inhibitor is useful in developing whitening cosmetics. Pyracantha koidzumii (Hayata) Rehder is an endemic species in Taiwan that exhibits tyrosinase-inhibitory activity. To find new active natural compounds from P. koidzumii, we performed bioguided isolation and studied the related activity in human epidermal melanocytes. In total, 13 compounds were identified from P. koidzumii in the present study, including two new compounds, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran (9) and 3,4-dihydroxy-5-methoxybiphenyl-2'-O-β-D-glucopyranoside (13), as well as 11 known compounds. The new compound 13 exhibited maximum potency in inhibiting cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-2, as well as the mRNA expression of Paired box 3 and microphthalmia-associated transcription factor in a concentration-dependent manner. In the enzyme kinetic assay, the new compound 13 acted as an uncompetitive mixed-type inhibitor against the substrate L-3,4-dihydroxyphenylalanine and had a Km value against this substrate of 0.262 mM, as calculated using the Lineweaver-Burk plots. Taken together, our findings show compound 13 exhibits tyrosinase inhibition in human melanocytes and compound 13 may be a potential candidate for use in cosmetics. [ABSTRACT FROM AUTHOR]

Aciculatin, a natural compound extracted from the medicinal herb Chrysopogon aciculatus, shows potent anti-cancer potency. This study is the first to prove that aciculatin induces cell death in human cancer cells and HCT116 mouse xenografts due to G1 arrest and subsequent apoptosis. The primary reason for cell cycle arrest and cell death was p53 accumulation followed by increased p21 level, dephosphorylation of Rb protein, PUMA expression, and induction of apoptotic signals such as cleavage of caspase-9, caspase-3, and PARP. We demonstrated that p53 allele-null (-/-) (p53-KO) HCT116 cells were more resistant to aciculatin than cells with wild-type p53 (+/+). The same result was achieved by knocking down p53 with siRNA in p53 wild-type cells, indicating that p53 plays a crucial role in aciculatin-induced apoptosis. Although DNA damage is the most common event leading to p53 activation, we found only weak evidence of DNA damage after aciculatin treatment. Interestingly, the aciculatin-induced downregulation of MDM2, an important negative regulator of p53, contributed to p53 accumulation. The anti-cancer activity and importance of p53 after aciculatin treatment were also confirmed in the HCT116 xenograft models. Collectively, these results indicate that aciculatin treatment induces cell cycle arrest and apoptosis via inhibition of MDM2 expression, thereby inducing p53 accumulation without significant DNA damage and genome toxicity. [ABSTRACT FROM AUTHOR]

Background: Critical thinking is essential in nursing practice. Promoting critical thinking competence in clinical nurses is an important way to improve problem solving and decision-making competence to further improve the quality of patient care. However, using an adequate tool to test nurses' critical thinking competence and disposition may provide the reference criteria for clinical nurse characterization, training planning, and resource allocation for human resource management. Purpose: The purpose of this study was to measure the critical thinking competence and critical thinking disposition of clinical nurses as well as to explore the related factors of critical thinking competence. Methods: Clinical nurses from four different clinical ladders selected from one medical center were stratified randomly. All qualified subjects who submitted valid questionnaires were included in the study. A Taiwan version of the modified Watson-Glaser Critical Thinking Appraisal and Critical Thinking Disposition Inventory was developed to measure the critical thinking competence and critical thinking disposition of clinical nurses. Validity was evaluated using the professional content test (content validity index = .93). Reliability was assessed with a Cronbach's alpha coefficient of .85. Data were analyzed using the SPSS for Windows (Version 12.0; SPSS Inc., Chicago, IL). Results: Results showed that competence of interpretation was the highest critical thinking competence factor. Inference was the lowest, and reflective thinking as a critical thinking disposition was more positive. In addition, age, years of nursing experience, and experiences in other hospitals significantly influenced critical thinking competence (p < .05). Factors of age, years of experience, and nurses clinical ladder were shown to affect critical thinking disposition scores. Clinical ladder N4 nurses had the highest scores in both competence and disposition. A significant relationship was found between critical thinking competence and disposition scores, with 29.3% of the variance in critical thinking competence potentially explained by total years of nurse hospital experience. Clinical ladder and age were predictive factors for critical thinking disposition. Commonality was 27.9%. Conclusions and Implications for Practice: Nursing experience and clinical ladders positively affect critical thinking competence and disposition. Issues of critical thinking competence increasingly need to be measured. Therefore, appropriate tools for nursing professions should be further developed and explored for specific areas of practice. [ABSTRACT FROM AUTHOR]

A seriesof N-sulfonyl-aminobiaryl derivativeshave been examined as novel antitubulin agents. Compound 21[N-(4′-cyano-3′-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide]exhibits remarkable antiproliferative activity against four cancercell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostatePC-3) with a mean GI50value of 57.5 nM. Additional assaysreveal that 21inhibits not only tubulin polymerizationbut also the phosphorylation of STAT3 inhibition with an IC50value of 0.2 μM. Four additional compounds (8, 10, 19, and 35) are alsoable to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potentanticancer agents targeting both STAT3 and tubulin. [ABSTRACT FROM AUTHOR]

Background: In order to improve treatment and care quality for cancer patients, nurse case management model has applied generally in the clinical practice. However there were only few evidence-based studies on the relative benefits in Taiwan. Further analysis and feedback application are needed. The aim of this study is to evaluate the effectiveness of care quality in cancer patients with nurse case management. Methods: This study was conducted with a quasi-experimental design in a national medical center in Northern Taiwan. Patients diagnosed as lung, liver, breast, colon, buccal or cervical cancers were eligible for inclusion. A total number of 600 subjects randomly selected from the cancer case management system enrolled in the case managed group, and 600 patients who received usual care were randomly selected from cancer registry and enrolled in the control group. The study instrument was developed to measure care effectiveness, including the rates of patient continuing treatment, non-adherence to treatment, prolonged hospitalization, unplanned readmission, and planned admission for active treatment. The content validity of expert was assessed as 0.9. Results: The nurse case management significantly decreased the unplanned readmission rate caused by infection (1.5% vs. 4.7% in the control group, p = 0.002). The rate of patient continuing treatment in the institution significantly increased in the case managed group (93.8% vs. 84.8% in the control group, p < 0.001). The planned admission rates in 14 days and in 15-30 days for active treatment also significantly increased in the case managed group (18.4.% vs. 3.9% in the control group and 34.5% vs. 10.4% in the control group, respectively, p < 0.001). The results indicated that nurse case management provided better control in timeliness and continuity of patient treatment. Conclusions: This study demonstrated that cancer case management could improve the effectiveness of cancer care services and concretely illustrated a comprehensive model for oncology patients in Taiwan. In addition, the model could be optimized for further application and improvement of cancer care. Future investigations are needed to develop precise and rigorous evaluation to optimize the utilization of cancer case management. [ABSTRACT FROM AUTHOR]

Although energy restriction has been recognized as an important target for cancer prevention, the mechanism by which energy restriction-mimetic agents (ERMAs) mediate apoptosis remains unclear, By using a novel thiazolidinedione-derived ERMA, CG-12 (Wei, S., Kuip, S. K., and Chen, C. S. (2010)1. Biol. Chem. 285, 9780-9791), vis-à-vis 2-deoxyglucose and glucose deprivation, we obtain evidence that epigenetic activation of the tumor suppressor gene Kruppel-like factor 6 (KLF6) plays a role in ERMA-induced apoptosis in LNCaP prostate cancer cells. KLF6 regulates the expression of many proapoptotic genes, and shRNA-mediated KLF6 knockdown abrogated the ability of ERMAs to induce apoptosis. Chromatin immunoprecipitation analysis indicates that this KLF6 transcriptional activation was associated with increased histone H3 acetylation and histone H3 lysine 4 trimethylation occupancy at the promoter region. Several lines of evidence demonstrate that the enhancing effect of ERMAs on these active histone marks was mediated through transcriptional repression of histone deacetylases and H3 lysine 4 demethylases by down-regulating Spi expression. First, putative Spi-binding elements are present in the promoters of the affected histone-modifying enzymes, and luciferase reporter assays indicate that site-directed mutagenesis of these Spi binding sites significantly diminished the promoter activities. Second, shRNA-mediated knockdown of Spi mimicked the repressive effect of energy restriction on these histone-modifying enzymes. Third, ectopic Spi expression protected cells from the repressive effect of CG-12 on these histone-modifying enzymes, thereby abolishing the activation of KLF6 expression. Together, these findings underscore the intricate relationship between energy restriction and epigenetic regulation of tumor suppressor gene expression, which has therapeutic relevance to foster novel strategies for prostate cancer therapy. [ABSTRACT FROM AUTHOR]