RESUMEN
Saikosaponin A (SSA)-a natural compound extracted from Radix bupleuri-possesses antitumor properties in several types of carcinomas. However, the role of SSA on bladder cancer and the mechanisms remain unclear. In this study, we have described the effect of SSA on human bladder cancer cell lines T24 and 5637 in the context of the regulation of mitochondrial pathways of apoptosis. In vitro, the Cell Counting Kit-8 (CCK-8) assay and cell wound healing assays were used to determine the proliferative effect of SSA treatment. Flow cytometry and Western blotting were performed to evaluate the apoptosis and related mechanisms. To further confirm that apoptosis is mediated through Caspase activation, Hoechst 33258 fluorescence staining assay was done after cells were treated with SSA and caspase inhibitor-Z-VAD-FMK. In vivo, an orthotopic xenograft mice model was adopted to evaluate the effect of SSA. The tumors were analyzed by hematoxylin-eosin (H&E) staining, immunohistochemical analysis, and Western blotting. In vitro, the results with CCK-8 assay showed obvious SSA-induced suppression in cell growth in a dose- and time-dependent manner. Flow cytometry analysis, Hoechst 33258 fluorescence staining assay and the assessment of the changes in the B-cell lymphoma 2 (Bcl-2) family protein expression level revealed that SSA could significantly induce cell apoptosis, which was associated with apoptosis via the mitochondrial pathways. In vivo, the results revealed a reduction in cell proliferation. In conclusion, our data suggest that SSA inhibits the growth of bladder cancer cells by activating the mitochondrial apoptosis pathway and inducing cell apoptosis.
Asunto(s)
Carcinoma , Neoplasias de la Vejiga Urinaria , Animales , Apoptosis , Bisbenzimidazol/farmacología , Caspasas , Línea Celular Tumoral , Proliferación Celular , Humanos , Ratones , Ácido Oleanólico/análogos & derivados , Saponinas , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
While the ability to coordinate movements temporally with rhythmic auditory stimuli is universal, previous investigators showed that accurate rhythm reproduction depends on temporal complexity. To date, the effect of multiple pitches on the timing of rhythmic movements has been assumed. Exploring a possible sustained entrainment effect of auditory stimuli on sequential movement might further elucidate the role of temporal complexity and its interaction with multiple pitch engagement. Thus, we investigated the sustained effect of auditory entrainment and the interaction between temporal complexity and pitch on predefined sequential tapping with tapping sequences predefined before a synchronization-timekeeping task. Temporal complexity was manipulated by increasing the number of non-integer ratios in temporal rhythm. The rhythm sequences were presented with either multiple pitches or a single pitch. We found a reduction in mean asynchronies and ratio error in three rhythms with non-integer ratios, while inter-response interval error was reduced in the integer rhythm and the rhythm with one repetitive integer ratio and one non-integer ratio. Ratio error remanence was less in rhythms with two non-integer ratios. We found no significant difference between the two pitch types. There was a sustained entrainment effect of sequential tapping that varied with differing temporal complexity, and pitch information was not essential for auditory entrainment. These findings provide support for possible interventions aimed at motor learning.
Asunto(s)
Percepción Auditiva , Movimiento , Humanos , Percepción Auditiva/fisiología , Estimulación Acústica , Movimiento/fisiologíaRESUMEN
The effects of auditory-motor entrainment have generally been investigated with periodic movements. Previous research has focused on how auditory-motor entrainment is influenced by the temporal structure of rhythms. The present study aimed to investigate whether auditory entrainment improved timing performance of sequential movements with varied path structures, and whether path complexity would affect any possible sustained effect of auditory entrainment. We also investigated whether the sustained effect was moderated by hearing single- vs. multiple-pitch audio prompts. Thirty participants were enrolled to perform a sequential finger-tapping task with discrete targets, in which the algebraic ratio relation of path lengths was manipulated as path complexity. Participants completed three stages per trial: initiation (to introduce the path sequence), entrainment (tapping along with the auditory and visual cues), and timekeeping (repeating the sequence without cues). We found timing improvement in terms of mean asynchronies and absolute interval error decrease after auditory entrainment. Only interval accuracy performance during timekeeping and entrainment was affected by path complexity. Moreover, no clear difference was observed between the rhythm sets in terms of single vs. multiple pitches. In conclusion, we found that phase and interval duration accuracy of predefined isochronous sequential movements with varied path complexity can be improved by auditory entrainment, and that auditory entrainment affects our performance beyond the actual presence of the auditory cue.