Curcuminoids Inhibit Angiogenic Behaviors of Human Umbilical Vein Endothelial Cells via Endoglin/Smad1 Signaling.

BACKGROUND: Angiogenesis is primarily attributed to the excessive proliferation and migration of endothelial cells. Targeting the vascular endothelial growth factor (VEGF) is therefore significant in anti-angiogenic therapy. Although these treatments have not reached clinical expectations, the upregulation of alternative angiogenic pathways (endoglin/Smad1) may play a critical role in drug (VEGF-neutralizing agents) resistance. Enhanced endoglin expression following a VEGF-neutralizing therapy (semaxanib®) was noted in patients. Treatment with an endoglin-targeting antibody augmented VEGF expression in human umbilical vein endothelial cells (HUVECs). Therefore, approaches that inhibit both the androgen and VEGF pathways enhance the HUVECs cytotoxicity and reverse semaxanib resistance. The purpose of this study was to find natural-occurring compounds that inhibited the endoglin-targeting pathway. METHODS: Curcuminoids targeting endoglin were recognized from two thousand compounds in the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan) using Discovery Studio 4.5. RESULTS: Our results, obtained using cytotoxicity, migration/invasion, and flow cytometry assays, showed that curcumin (Cur) and demethoxycurcumin (DMC) reduced angiogenesis. In addition, Cur and DMC downregulated endoglin/pSmad1 phosphorylation. CONCLUSIONS: The study first showed that Cur and DMC demonstrated antiangiogenic activity via the inhibition of endoglin/Smad1 signaling. Synergistic effects of curcuminoids (i.e., curcumin and DMC) and semaxanib on HUVECs were found. This might be attributed to endoglin/pSmad1 downregulation in HUVECs. Combination treatment with curcuminoids and a semaxanib is therefore expected to reverse semaxanib resistance.

Electrophysiological investigation of the effects of Tai Chi on inhibitory control in older individuals.

The possibility that improved inhibitory control in older adults is associated with engagement in non-contact sporting activity, Tai Chi, was investigated. Three groups of participants were compared; a group who regularly took part in Tai Chi (TC), a regularly exercising (RE) group, and a sedentary group (SG). Concurrent electroencephalographic recordings were obtained while a stop-signal inhibitory control task, where speeded responses are needed for most trials, but these must occasionally be withheld when a 'stop signal' is displayed, was performed. The electrophysiological components P3, broadly related to decision making, and Pe, related to error monitoring, were analyzed. Both exercise groups performed better on the stop-signal task for the measure indicative of inhibitory control, as well as being generally better for other indices of performance. No significant effects were seen for post-error slowing. Electrophysiological differences were seen for the TC group, with a significantly larger P3 component related to the stop-signal and a larger Pe component when errors were made. This indicated that the TC group seemed to show better decision making and have better awareness of errors. Future work should investigate whether such effects are seen when this type of exercise is applied as an 'intervention' in non-exercising individuals.

Epigallocatechin-3-gallate inhibits tumor angiogenesis: involvement of endoglin/Smad1 signaling in human umbilical vein endothelium cells.

Strategies targeting endoglin are currently being investigated in clinical trials as an anti-angiogenic therapy. The redundancy between endoglin and vascular endothelial growth factor (VEGF) signaling in angiogenesis was verified. Increased endoglin signaling after an anti-VEGF treatment was observed in patients. Treatment with an endoglin-neutralizing antibody increased VEGF signaling in endothelial cells. Therefore, strategies targeting both the endoglin and VEGF pathways were applied to determine whether the anti-angiogenic effects were increased in vitro. Five possible hits for endoglin were identified from 2000 compounds in the Traditional Chinese Medicine Database using Discovery Studio 4.5 Epigallocatechin-3-gallate (EGCG) attenuates angiogenesis by downregulating VEGF; however, researchers have not determined whether its anti-angiogenic effects are mediated by endoglin/Smad1 signaling. A major contribution of this study is that EGCG significantly inhibited the upregulation of endoglin in semaxanib-treated human umbilical vein endothelial cell. Thus, a combination treatment with EGCG and a VEGF tyrosine kinase inhibitor would be appropriate to reverse drug resistance. EGCG alone significantly decreased endoglin/pSmad1 levels in HUVECs. In the angiogenesis assay, the migration, invasion, and tube formation of HUVECs were markedly suppressed by higher concentrations of EGCG. A combination treatment with EGCG and semaxanib further produced increased anti-angiogenic effects. The main contribution of the study indicated that EGCG significantly decreased the semaxanib-induced overexpression of endoglin. Therefore, a combination treatment including EGCG will probably solve the drug resistance to anti-VEGF treatments.

A cross-sectional evaluation of meditation experience on electroencephalography data by artificial neural network and support vector machine classifiers.

To quantitate the meditation experience is a subjective and complex issue because it is confounded by many factors such as emotional state, method of meditation, and personal physical condition. In this study, we propose a strategy with a cross-sectional analysis to evaluate the meditation experience with 2 artificial intelligence techniques: artificial neural network and support vector machine. Within this analysis system, 3 features of the electroencephalography alpha spectrum and variant normalizing scaling are manipulated as the evaluating variables for the detection of accuracy. Thereafter, by modulating the sliding window (the period of the analyzed data) and shifting interval of the window (the time interval to shift the analyzed data), the effect of immediate analysis for the 2 methods is compared. This analysis system is performed on 3 meditation groups, categorizing their meditation experiences in 10-year intervals from novice to junior and to senior. After an exhausted calculation and cross-validation across all variables, the high accuracy rate >98% is achievable under the criterion of 0.5-minute sliding window and 2 seconds shifting interval for both methods. In a word, the minimum analyzable data length is 0.5 minute and the minimum recognizable temporal resolution is 2 seconds in the decision of meditative classification. Our proposed classifier of the meditation experience promotes a rapid evaluation system to distinguish meditation experience and a beneficial utilization of artificial techniques for the big-data analysis.