IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma

Predicting and overcoming radioresistance are crucial in radiation oncology, including in managing oral squamous cell carcinoma (OSCC). First, we used RNA-sequence to compare expression profiles of parent OML1 and radioresistant OML1-R OSCC cells in order to select candidate genes responsible for radiation sensitivity. We identified IRAK2, a key immune mediator of the IL-1R/TLR signaling, as a potential target in investigating radiosensitivity. In four OSCC cell lines, we observed that intrinsically low IRAK2 expression demonstrated a radioresistant phenotype (i.e., OML1-R and SCC4), and vice versa (i.e., OML1 and SCC25). Next, we overexpressed IRAK2 in low IRAK2-expression OSCC cells and knocked it down in high IRAK2-expression cells to examine changes of irradiation response. After ionizing radiation (IR) exposure, IRAK2 overexpression enhanced the radiosensitivity of radioresistant cells and synergistically suppressed OSCC cell growth both in vitro and in vivo, and vice versa. We found that IRAK2 overexpression restored and enhanced radiosensitivity by enhancing IR-induced cell killing via caspase-8/3-dependent apoptosis. OSCC patients with high IRAK2 expression had better post-irradiation local control than those with low expression (i.e., 87.4% vs. 60.0% at five years, P = 0.055), showing that IRAK2 expression was associated with post-radiation recurrence. Multivariate analysis confirmed high IRAK2 expression as an independent predictor for local control (HR, 0.11; 95% CI, 0.016 – 0.760; P = 0.025). In conclusion, IRAK2 enhances radiosensitivity, via modulating caspase 8/3-medicated apoptosis, potentially playing double roles as a predictive biomarker and a novel therapeutic target in OSCC

Unusual Field Dependence of the Anomalous Hall Effect in Ta/Tb-Fe-Co

Contains fulltext : 224981.pdf (publisher's version ) (Open Access

Amplitudes of motor evoked potential (% of M-response) during active conditions.

<p>Data are presented as the mean ± SEM.</p>a, b,<p>and^c indicate significant differences between the R FCR task and the R AD task, between the R FCR task and the R RF task, and between the R FCR task and the R TA task, respectively. Significance level was set at <i>P</i><0.05. RMT: resting motor threshold. R: right; AD: anterior deltoid; FCR: flexor carpi radialis; RF: rectus femoris; TA: tibialis anterior.</p

Short-interval intracortical inhibition (%, SICI) during active conditions.

<p>Data are presented as the mean ± SD.</p>a, b,<p>and^c indicate significant differences between the R FCR task and the R AD task, between the R FCR task and the R RF task, and between the R FCR task and the R TA task, respectively. Significance level was set at <i>P</i><0.05. R: right; AD: anterior deltoid; FCR: flexor carpi radialis; RF: rectus femoris; TA: tibialis anterior.</p

Increased corticospinal output and decreased intracortical inhibition of the left rectus femoris (L RF) muscle during unilateral motor task.

<p>(A) Recruitment curves of motor evoked potential (MEP) at rest and during four active conditions that were performed by muscles on the right side. The abscissa shows intensity of transcranial magnetic stimulus expressed relative to the resting motor threshold in each subject. The ordinate shows MEP amplitudes as a percentage of the M-responses collected via femoral nerve magnetic stimulation (M-response_FNMS). Data are presented as the mean ± standard error from all 15 subjects. (B) Ratio of short-interval intracortical inhibition (SICI) at rest and during four active conditions. The size of the conditioned MEP is expressed as a percentage of the amplitude of the test MEP (horizontal dotted line). Data are presented as the mean ± standard deviation from all 15 subjects. Asterisks indicate statistically significant differences from the rest condition (*<i>p</i><0.05) by repeated-measures ANOVA following a post hoc contrast test. R: right; AD: anterior deltoid; FCR: flexor carpi radialis; RF: rectus femoris; TA: tibialis anterior.</p

Combination of rTMS and Treadmill Training Modulates Corticomotor Inhibition and Improves Walking in Parkinson Disease

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability. Combinations of rehabilitation therapies with rTMS might enhance the therapeutic effects.OBJECTIVE: The purpose of this study was to investigate the effects of high-frequency rTMS followed by treadmill training on cortical inhibition and walking function in individuals with Parkinson disease (PD).METHODS: A total of 20 patients with PD were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by treadmill training (30 minutes) for 12 sessions over 4 weeks. Repetitive TMS was applied at a 5-Hz frequency over the leg area of the motor cortex contralaterally to the more affected side for 6 minutes. Outcomes, including corticomotor inhibition and walking performance, were measured before and after training.RESULTS: . The results showed significant time effects on almost all corticomotor and functional variables. There are significant interaction effects between group and time of evaluation on the motor threshold, duration of the cortical silent period, and short interval intracortical inhibition of the contralateral hemisphere relatively to the more affected side as well as on the fast walking speed and timed up and go.CONCLUSIONS: The findings suggested that combination of rTMS and treadmill training enhances the effect of treadmill training on modulation of corticomotor inhibition and improvement of walking performance in those with PD.</p