BACKGROUND PAX6, a transcription factor, has currently been suggested to function as a tumor suppressor in glioblastoma and to act as an early differentiation marker for neuroendocrine cells. The androgen receptor (AR) plays a pivotal role in prostate cancer development and progression due to its transcriptional activity in regulating genes involved in cell growth, differentiation, and apoptosis. To determine the role of PAX6 in prostate cancer, we investigated whether PAX6 interacts with AR to affect prostate cancer development. METHODS We used immunostaining, RT-PCR, and western blotting assays to show the expression status of PAX6 in prostate tissue and human prostate cancer cell lines. The role of PAX6 in cell growth and colony regeneration potential of LNCaP cells were evaluated by MTT assay and soft agar assay with PAX6-overexpressed LNCaP cells. Mammalian two-hybrid and coimmunoprecipitation (CoIP) assays were used to demonstrate the interaction between PAX6 and AR. Reporter gene and Q-RT-PCR assays were performed to determine the effects of PAX6 on the function of AR. RESULTS In prostate cancer tissues, PAX6 expression was stronger in normal epithelial cells than cancer cells, and decreased in LNCaP cells compared to that of DU145 and PC3 cells. Enforced expression of PAX6 suppressed the cell growth of LNCaP cells and also inhibited the colony formation of LNCaP cells. PAX 6 interacted with AR and repressed its transcriptional activity. PAX6 overexpression decreased the expression of androgen target gene PSA in LNCaP cells. CONCLUSIONS In this study, we found that PAX6 may act as a prostate cancer repressor by interacting with AR and repressing the transcriptional activity and target gene expression of AR to regulate cell growth and regeneration.
Background Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation to modulate cortical activity for improving motor function. However, the different tDCS applications for modulating cortical activity and dual task gait performance in chronic stroke have not yet been investigated. This study investigated the effects of different tDCS applications on dual task gait performance and contralesional M1 activation in chronic stroke. Methods Forty-eight participants were randomized to anodal, bilateral, cathodal, and sham tDCS groups. Each group received 20 min of tDCS stimulation, except the sham group. Gait performance was measured by GaitRite system during cognitive dual task (CDT) walking, motor dual task (MDT) walking, and single walking (SW). Contralesional M1 activity of unaffected tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). Intragroup difference was analyzed by Wilconxon sign ranks test with Bonferroni correction, and Kruskal–Wallis one-way analysis of variance by ranks was used for intergroup comparisons, followed by post-hoc Mann–Whitney U tests with Bonferroni correction. Results The bilateral tDCS (p = 0.017) and cathodal tDCS (p = 0.010) improved the CDT walking speed more than sham group. The bilateral tDCS (p = 0.048) and cathodal tDCS (p = 0.048) also improved the MDT walking speed more than sham group. Furthermore, bilateral tDCS (p = 0.012) and cathodal tDCS (p = 0.040) increased the silent period (SP) more than the anodal and sham group. Thus, one-session of bilateral and cathodal tDCS improved dual task walking performance paralleled with increasing contralesional corticomotor inhibition in chronic stroke. Conclusions Our results indicate that one-session of bilateral and cathodal tDCS increased contralesional corticomotor inhibition and improved dual task gait performance in chronic stroke. Trial registration Thai Clinical Trials Registry (TCTR20180116001). Registered prospectively on 16th Jan, 2018 at http://www.thaiclinicaltrials.org.
BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation to modulate cortical activity for improving motor function. However, the information of tDCS stimulation on different brain regions for dual-task walking and cortical modulation in Parkinson’s disease (PD) has not yet been compared.ObjectiveThe objective of this study was to investigate the effects of different tDCS targets on dual-task gait performance and cortical activity in patients with PD.MethodsA total of 36 participants were randomly assigned to primary motor cortex (M1) tDCS, dorsal lateral prefrontal cortex (DLPFC) tDCS, cerebellum tDCS, or Sham tDCS group. Each group received 20 min of tDCS stimulation, except for the Sham group. Gait performance was measured by the GAITRite system during dual-task walking and single walking. Corticomotor activity of the tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). The functional mobility was assessed using the timed up and go (TUG) test.ResultsAll participants showed no significant differences in baseline data. Following the one session of tDCS intervention, M1 (p = 0.048), DLPFC (p < 0.001), and cerebellum (p = 0.001) tDCS groups demonstrated significant improvements in dual-task gait speed compared with a pretest. The time × group interaction [F(3, 32) = 5.125, p = 0.005] was detected in dual-task walking speed. The post hoc Tukey’s test showed that the differences in gait speed were between the Sham tDCS group and the DLPFC tDCS group (p = 0.03). Moreover, DLPFC tDCS also increased the silent period (SP) more than M1 tDCS (p = 0.006) and Sham tDCS (p = 0.002).ConclusionThe results indicate that DLPFC tDCS exerted the most beneficial effects on dual-task walking and cortical modulation in participants with PD.Clinical trial registration[http://www.thaiclinicaltrials.org/show/TCTR20200909005], Thai Clinical Trials Registry [TCTR20200909005].
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