Dosage effects of curcumin on cell death types in a human osteoblast cell line.

Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties, as well as their ability to either induce or prevent cell apoptosis. However, the precise molecular mechanisms of these effects are unknown. Here, we demonstrate that curcumin can induce apoptotic changes, including JNK activation, caspase-3 activation, and cleavage of PARP and PAK2, at treatment concentrations lower than 25 microM in human osteoblast cells. In contrast, treatment with 50-200 microM of curcumin does not induce apoptosis, but rather triggers necrotic cell death in human osteoblasts. Using the cell permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we found that while treatment with 12.5-25 microM curcumin directly increased intracellular oxidative stress, 50-200 microM curcumin had far less effect. Pretreatment of cells with N-acetyl cysteine or alpha-tocopherol, two well known ROS scavengers, attenuated the intracellular ROS levels increases and converted the apoptosis to necrosis induced by 12.5-25 microM curcumin. Moreover, we observed a dose-dependent decrease in intracellular ATP levels after treatment of osteoblast cells with curcumin and pretreatment of cells with antimycin or 2-deoxyglucose to cause ATP depletion significantly converted 12.5-25 microM curcumin-induced apoptosis to necrosis, indicating that ATP (a known mediator of apoptotic versus necrotic death) is most likely involved in the switching mechanism. Overall, our results signify that curcumin dosage treatment determines the possible effect on ROS generation, intracellular ATP levels, and cell apoptosis or necrosis in osteoblast cells.

Sleep-related predictors of quality of life in the elderly versus younger heart failure patients: a questionnaire survey.

BACKGROUND: Research has indicated that sleep disorders reduce the quality of life of heart failure patients. OBJECTIVES: To investigate quality of sleep, and the impact of poor sleep on quality of life among elderly versus younger heart failure patients. DESIGN: A two-group, cross-sectional study. SETTING: A community teaching hospital in Taipei, Taiwan. PARTICIPANTS: Voluntarily self-enrolled heart failure patients who did not have sleep apnea or restless leg syndrome. METHODS: There were 126 elderly and 67 young participants filled out five questionnaires (1) demographic information and current health status; (2) the Chinese Pittsburgh Sleep Quality Index; (3) the Chinese Epworth Sleepiness Scale, and (4) the short form (SF)-36 Taiwanese version. The major statistical procedures applied in this study were t-test, analysis of variance, Pearson's correlation, and a stepwise multiple linear regression. A p-value of <0.05 was adopted as significant. RESULTS: The prevalence of insomnia was 44.4% for the elderly group and 31.4% for the younger group. The top three prevalence sleep-disturbing events were: nocturia, long sleep latency, and early wake-up. In the elderly group, nocturnal dyspnea and long sleep latency were significant determinants of the mental (R(2)=0.23) and physical components (R(2)=0.21) of quality of life. In the young group, nocturnal dyspnea was a significant determinant of the mental component of quality of life (R(2)=0.15), and early wake-up was a significant determinant of the physical component of quality of life (R(2)=0.15). CONCLUSION: The sleep disorder of heart failure patients is disease-specific rather than a matter of age. The prevalence of insomnia of young heart failure patients was higher than that of the healthy elderly. The major determinants of poor night sleep quality in the elderly group were dyspnea and long sleep latency, and in the younger group, these were dyspnea and early wake-up. Those also were significant determinants of quality of life of the heart failure patients. IMPLICATIONS FOR NURSING PRACTICE: Since the sleep-related predictors of quality of life were different in the elderly versus younger heart failure patients, to identify the insomnia factors individually and to provide guidance of appropriate usage of sleep medications and other methods to promote sleep should be considered.

Characterization and application of single fluorescent nanodiamonds as cellular biomarkers.

Type Ib diamonds emit bright fluorescence at 550-800 nm from nitrogen-vacancy point defects, (N-V)(0) and (N-V)(-), produced by high-energy ion beam irradiation and subsequent thermal annealing. The emission, together with noncytotoxicity and easiness of surface functionalization, makes nano-sized diamonds a promising fluorescent probe for single-particle tracking in heterogeneous environments. We present the result of our characterization and application of single fluorescent nanodiamonds as cellular biomarkers. We found that, under the same excitation conditions, the fluorescence of a single 35-nm diamond is significantly brighter than that of a single dye molecule such as Alexa Fluor 546. The latter photobleached in the range of 10 s at a laser power density of 10(4) W/cm(2), whereas the nanodiamond particle showed no sign of photobleaching even after 5 min of continuous excitation. Furthermore, no fluorescence blinking was detected within a time resolution of 1 ms. The photophysical properties of the particles do not deteriorate even after surface functionalization with carboxyl groups, which form covalent bonding with polyL-lysines that interact with DNA molecules through electrostatic forces. The feasibility of using surface-functionalized fluorescent nanodiamonds as single-particle biomarkers is demonstrated with both fixed and live HeLa cells.