Yu-Yawn Chen

Platonin induces autophagy-associated cell death in human leukemia cells.

Platonin is a photosensitizer used for photodynamic therapy. In this study, we tested the effect of platonin on human leukemic cells. Treatment with platonin in the dark markedly reduced cell membrane integrity, and induced significant G0/G1 arrest of a panel of human leukemic cell lines, including U937, HL-60, K562, NB4 and THP-1. Development of hypodiploid cells was not evident in these cell lines within 24 h, but was noted in U937, HL-60 and NB4 cells after 24 h. No myeloid differentiation of these cells was noted after 5-day treatment. Intriguingly, exposure of monoblastic U937 cells to platonin caused changes characteristic of autophagy, including appearance of cytoplasmic membranous vacuoles and formation of acidic vesicular organelles (AVO) in more than 95% of cells. The platonin-induced autophagy was accompanied by localization of microtubule-associated protein 1 light chain 3 to autophagosomes. Pretreatment with pancaspase inhibitor Z-VAD-fmk abrogated the platonin-induced hypodiploidity, but had no effect on growth inhibition and formation of AVO, indicating a caspase-independent autophagy-associated cell death. Pretreatment of cells with 3-methyladenine attenuated platonin-mediated growth inhibition and formation of AVO. Platonin augmented the expression of BNIP3 in both U937 and K562 cells, whereas had an opposite effect on phosphorylation of mTOR downstream molecule p70S6K. Platonin, at the condition inducing autophagy, induced the mitochondrial membrane permeation. These results suggest that the platonin is capable of inhibiting growth as well as inducing cell death, mainly autophagy-associated, in leukemic cells via a mitochondria-mediated and caspase-independent pathway. A markedly less viability inhibition was noted to human monocytes, the normal counterpart of these myeloid leukemic cells. Platonin, other than a photodynamic agent, may offer significant promise as a therapeutic agent against leukemia.

Predicting body composition using foot-to-foot bioelectrical impedance analysis in healthy Asian individuals.

BackgroundThe objectives of this study were to develop a regression model for predicting fat-free mass (FFM) in a population of healthy Taiwanese individuals using standing foot-to-foot bioelectrical impedance analysis (BIA) and to test the model’s performance in predicting FFM with different body fat percentages (BF%).MethodsWe used dual-energy X-ray absorptiometry (DXA) to measure the FFM of 554 healthy Asian subjects (age, 16–75 y; body mass index, 15.8–43.1xa0kg/m2). We also evaluated the validity of the developed multivariate model using a double cross-validation technique and assessed the accuracy of the model in an all-subjects sample and subgroup samples with different body fat levels.ResultsPredictors in the all-subjects multivariate model included height2/impedance, weight, year, and sex (FFMu2009=u200913.055u2009+u20090.204 weightu2009+u20090.394 height2/Impedance – 0.136 ageu2009+u20098.125 sex (sex: Femaleu2009=u20090, Maleu2009=u20091), r2u2009=u20090.92, standard error of the estimateu2009=u20093.17xa0kg). The correlation coefficients between predictive FFM by BIA (FFMBIA) and DXA-measured FFM (FFMDXA) in female subjects with a total-subjects BF%DXA of <20xa0%, 20xa0%–30xa0%, 30xa0%–40xa0% and >40xa0% were ru2009=u20090.87, 0.90, 0.91, 0.89, and 0.94, respectively, with biasu2009±u20092SD of 0.0u2009±u20093.0xa0kg, −2.6u2009±u20091.7xa0kg, −1.5u2009±u20092.8xa0kg, 0.5u2009±u20092.7xa0kg, and 2.0u2009±u20092.9xa0kg, respectively. The correlation coefficients between FFMBIA and FFMDXA in male subjects with a total-subjects BF%DXA of <10xa0%, 10xa0%–20xa0%, 20xa0%–30xa0%, and >30xa0% were ru2009=u20090.89, 0.89, 0.90, 0.93, and 0.91, respectively, with biasu2009±u20092SD of 0.0u2009±u20093.2xa0kg, −2.3u2009±u20092.5xa0kg, −0.5u2009±u20093.2xa0kg, 0.4u2009±u20093.1xa0kg, and 2.1u2009±u20093.2xa0kg, respectively.ConclusionsThe standing foot-to-foot BIA method developed in this study can accurately predict FFM in healthy Asian individuals with different levels of body fat.

Tai Chi Chuan Increases Circulating Myeloid Dendritic Cells

Dendritic cells, the most potent antigen-presenting cells linking innate and adoptive immunity, are thought to be important targets of immune modulators such as exercise. We examined the effect of Tai Chi Chuan (TCC) on dendritic cells. TCC practitioners were further divided to high-level practitioners (TCC-H) and low-level practitioners (TCC-L). The quantities of myeloid and plasmacytoid dendritic cells were estimated by flow cytometry. We examined parameters including age, body weight, body length, body fat, and serum albumin level, in the controls, TCC-H and TCC-L, which did not differ significantly. The mean peak (volume of O2 utilization) of the TCC-H group was greater than that of the sedentary control group. White blood cell (WBC) count in the entire TCC group was greater than that of the controls. The quantity of myeloid dendritic cells was significantly greater in the TCC group, whereas the quantity of plasmacytoid dendritic cells was similar for both groups. Among the TCC subgroups, the quantity of myeloid dendritic cells, but not plasmacytoid dendritic cells, in the TCC-H group was greater than that of TCC-L practitioners. TCC could increase the number of circulating myeloid dendritic cells, but not plasmacytoid dendritic cells, in a performance level-dependent manner.

MIDDLE-AGED SUBJECTS WITH HABITUAL LOW-SPEED CYCLING EXERCISE HAVE GREATER MONONUCLEAR CELL RESPONSIVENESS AGAINST HUMAN HEPATITIS B VIRUS SURFACE ANTIGEN

SUMMARY Background: Whether middle-aged people with habitual cycling exercise (HCE) at low intensity in the morning have higher immunity against hepatitis B virus than sedentary controls (SCs) is a health issue in the elderly. Methods: Conditioned media (CM) were prepared by stimulating isolated human peripheral blood mononu- clear cells (MNC) with phytohemagglutinin (PHA) or assessment of their inhibitory effects on hepatitis B surface antigen expression in human hepatoma Hep3B cells. Results: With the percent of maximal oxygen uptake at about 45.52% and percent of maximal heart rate at about 68.58% during a cycling exercise program in the present study, we considered HCE as an aerobic and a low to mod- erate exercise for the elderly. The concentrations of secreted cytokines such as interferon gamma, tumor necro- sis factor α and interferon alpha were higher in the MNC-CM from the HCE group than from the SC group. The inhibitory rates of MNC-CM of the HCE group against hepatitis B surface antigen expression were higher than that of the SC group. In the same stimulating concentration of PHA (10 μg/mL), the relative hepatitis B surface anti- gen expression in MNC-CM of the HCE group was 64.7% versus 81.5% of the SC group. The reduction in inhibitory rates in cytokine neutralization experiments suggests crucial roles of these cytokines for the inhibitory effect of HCE-PHA-MNC-CM against hepatitis B surface antigen expression. Conclusion: The results reveal that the immune response of MNC, which are stimulated by PHA to suppress hep- atitis B surface antigen expression, is greater in middle-aged subjects with low-speed HCE than in sedentary subjects. (International Journal of Gerontology 2010; 4(2): 82-88)

Hand-to-Hand Model for Bioelectrical Impedance Analysis to Estimate Fat Free Mass in a Healthy Population

This study aimed to establish a hand-to-hand (HH) model for bioelectrical impedance analysis (BIA) fat free mass (FFM) estimation by comparing with a standing position hand-to-foot (HF) BIA model and dual energy X-ray absorptiometry (DXA); we also verified the reliability of the newly developed model. A total of 704 healthy Chinese individuals (403 men and 301 women) participated. FFM (FFMDXA) reference variables were measured using DXA and segmental BIA. Further, regression analysis, Bland–Altman plots, and cross-validation (2/3 participants as the modeling group, 1/3 as the validation group; three turns were repeated for validation grouping) were conducted to compare tests of agreement with FFMDXA reference variables. In male participants, the hand-to-hand BIA model estimation equation was calculated as follows: FFMmHH = 0.537 h2/ZHH − 0.126 year + 0.217 weight + 18.235 (r2 = 0.919, standard estimate of error (SEE) = 2.164 kg, n = 269). The mean validated correlation coefficients and limits of agreement (LOAs) of the Bland–Altman analysis of the calculated values for FFMmHH and FFMDXA were 0.958 and −4.369–4.343 kg, respectively, for hand-to-foot BIA model measurements for men; the FFM (FFMmHF) and FFMDXA were 0.958 and −4.356–4.375 kg, respectively. The hand-to-hand BIA model estimating equation for female participants was FFMFHH = 0.615 h2/ZHH − 0.144 year + 0.132 weight + 16.507 (r2 = 0.870, SEE = 1.884 kg, n = 201); the three mean validated correlation coefficient and LOA for the hand-to-foot BIA model measurements for female participants (FFMFHH and FFMDXA) were 0.929 and −3.880–3.886 kg, respectively. The FFMHF and FFMDXA were 0.942 and −3.511–3.489 kg, respectively. The results of both hand-to-hand and hand-to-foot BIA models demonstrated similar reliability, and the hand-to-hand BIA models are practical for assessing FFM.

Comparison of Standing Posture Bioelectrical Impedance Analysis with DXA for Body Composition in a Large, Healthy Chinese Population

Bioelectrical impedance analysis (BIA) is a common method for assessing body composition in research and clinical trials. BIA is convenient but when compared with other reference methods, the results have been inconclusive. The level of obesity degree in subjects is considered to be an important factor affecting the accuracy of the measurements. A total of 711 participants were recruited in Taiwan and were sub-grouped by gender and levels of adiposity. Regression analysis and Bland-Altman analysis were used to evaluate the agreement of the measured body fat percentage (BF%) between BIA and DXA. The BF% measured by the DXA and BIA methods (Tanita BC-418) were expressed as BF%DXA and BF%BIA8, respectively. A one-way ANOVA was used to test the differences in BF% measurements by gender and levels of adiposity. The estimated BF%BIA8 and BF%DXA in the all subjects, male and female groups were all highly correlated (r = 0.934, 0.901, 0.916, all P< 0.001). The average estimated BF%BIA8 (22.54 ± 9.48%) was significantly lower than the average BF%DXA (26.26 ± 11.18%). The BF%BIA8 was overestimated in the male subgroup (BF%DXA< 15%), compared to BF%DXA by 0.45%, respectively. In the other subgroups, the BF%BIA8 values were all underestimated. Standing BIA estimating body fat percentage in Chinese participants have a high correlation, but underestimated on normal and high obesity degree in both male and female subjects.

Abstract 2148: Thalidomide and liposomal doxorubicin inhibit differentiation and function of human osteoclasts

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLnnBackground: Thalidomide inhibits angiogenesis and growth of multiple myeloma. Liposomal doxorubicin is mainly absorbed and degraded by monocyte-macrophage lineage in vivo, implicating a possible targeting effect. Given that osteoclasts (OCs) are derived from precursors of monocyte-macrophage lineage, we hypothesized that thalidomide, liposomal doxorubicin and their combination may affect osteoclastogenesis.nnMaterials and Methods: We isolated CD14+ monocytes from peripheral blood mononuclear cells of healthy subjects and generated OCs under stimulation with macrophage-colony forming factor and receptor activator of NK-κB ligand. Cell viability, surface CD51/61 expression, and tartrate-resistant acid phosphatase (TRAP) activity were assessed by using MTT, flow cytometry and immunohistochemical staining, respectively. Bone resorption activity of OCs was examined.nnResults: The combination of thalidomide (purchased from TTY Biopharm, Taiwan) and liposomal doxorubicin (purchased from TTY Biopharm, Taiwan) profoundly inhibited the amount of harvested viable OCs. The expression of osteoclast-specific surface antigen CD51/61 was markedly inhibited by each drug and their combination. Specifically, the amount of multinucleated TRAP-positive cells characteristics of OCs and bone resorption activity of OCs were suppressed by each drug and, the mostly, their combination.nnConclusion: Thalidomide, liposomal doxorubicin and their combination, beyond currently clinical indications, might be effective regimen to inhibit human osteoclastogenesis.nnCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2148. doi:10.1158/1538-7445.AM2011-2148

Abstract 3806: Stimulation of anti-leukemia immune response by a rice protein prolamin

Rice (Oryza sativa), an important cereal as a staple food worldwide, has been demonstrated that its water extracts benefit anti-leukaemia immunity. The present study isolated and characterized the active rice proteins and assessed the anti-leukemia response via in vitro and ex vivo experiments. Proteomic analysis identified various protein spots known with functions involving metabolism-related, transport, storage, antioxidation, development, and disease resistance proteins. Among these, storage proteins were the most abundant. To avoid masking the other relatively scanty rice storage proteins, albumin, globulin, glutelin and prolamin were separated and quantified. Prolamin-prepared conditioned medium of human mononuclear cells (MNC-CM) showed the greatest inhibition of human leukaemia U937 cell growth. Prolamin enhanced MNC to secrete tumor necrosis factor-α and prolamin-prepared MNC-CM induced U937 cells toward monocyte differentiation, not only by morphological observation, but also by NBT-reduction test. Neutralization of prolamin by polyclonal antibody attenuated its activity. Prolamin has greater activity than wheat gluten (glutenin and gliadin), which can cause celiac disease (CD). Additionally, rice proteins were undetectable by wheat gliadin-specific antibody, suggesting that rice may be an ideal candidate of food substitute in CD patients. In conclusion, rice prolamin is effective in activating human anti-leukaemia immunity and may not induce unwanted inflammatory diseases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3806.

Abstract 1661: Effect of thalidomide and liposomal doxorubicin on human osteoclastogenesis

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCnnBackground: Thalidomide has been reported capable of inhibiting angiogenesis and growth of multiple myeloma. Liposomal doxorubicin is known to be mainly absorbed and degraded in reticuloendothelial system, especially the monocyte-macrophage lineage. Since osteoclasts (OCs) are derived from precursors of monocyte-macrophage lineage, we aimed to examine the effect of thalidomide, liposomal doxorubicin and their combination on human osteoclastogenesis.nnMaterials and Methods: We isolated CD14+ cells from peripheral blood mononuclear cells of healthy subjects and generated OCs under stimulation with macrophage-colony forming factor and receptor activator of NK-κB ligand. Cell viability, surface CD51/61 expression, and tartrate-resistant acid phosphatase (TRAP) activity were assessed by using MTT, flow cytometry and immunohistochemical staining, respectively.nnResults: In comparison with control differentiated OCs, combination of thalidomide (purchased from TTY Biopharm, Taiwan) and liposomal doxorubicin (purchased from TTY Biopharm, Taiwan) profoundly inhibited the amount of harvested viable OCs. By treatment with each drug alone, thalidomide increased and liposomal doxorubicin decreased the amount of viable OCs. The expression of osteoclast-specific surface antigen CD51/61 was greatly inhibited by each drug and their combination. Furthermore, the amount of multinucleated TRAP-positive cells characteristics of OCs, was suppressed by each drug and, the mostly, their combination. Elucidation of cellular and molecular mechanisms of action has been undergoing.nnConclusion: Thalidomide, liposomal doxorubicin and their combination may effectively inhibit human osteoclastogenesis.nnCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1661.