Search

Aims: In this study, we examined whether β-apopicropodophyllin (APP) could act as a radiosensitizer in non-small cell lung cancer (NSCLC) cells. Main methods: The in vitro radiosensitizing activity of APP was demonstrated with clonogenic assay, immunoblotting, Annexin V-Propidium iodide (PI) assay, BrdU incorporation, detection of mitochondrial ROS/intracellular of H2O2, mitochondrial membrane potential detection, and performing of isolation of mitochondrial and cytosolic fractions. The in vivo radiosensitizing activity of APP was determined in xenografted mice with co-treatment of APP and IR based on measurement of tumor volumes and apoptotic cell death. Key findings: The results of a clonogenic assay indicated that a combination of APP and γ-ionizing radiation (IR) inhibits cell growth and increases cell death in NSCLC cells. Several signal transduction pathways were examined for their potential involvement in the apparent radiosensitization effect of APP, as assessed by immunoblotting analyses and mitochondrial potential determination in vitro. Treatment of NCI-H460 cells with 15 nM APP and NCI-H1299 cells with 10 nM APP yielded dose-enhancement ratios of 1.44 and 1.24, respectively. Enhanced ER stress, disrupted mitochondrial membrane potential, and increased reactive oxygen species (ROS) were observed in cells co-treated with APP and IR, and this was followed by the cytosolic release of cytochrome c and consequent activation of caspase-3 and -9. Notably, inhibition of JNK, which prevents caspase activation, blocked the APP/IR-induced activations of ER stress and apoptotic cell death. In NCI-H460 or NCI-H1299 cell-xenografted mice, APP/IR treatment delayed the time it took tumors to reach a threshold size by 22.38 and 16.83 days, respectively, compared with controls, to yield enhancement factors of 1.53 and 1.38, respectively. Significance: APP has a radiosensitizing function derived from its ability to induce apoptotic cell death via activation of ER stress, disruption of mitochondrial membrane potential, and induction of the caspase pathway.

Previously, we demonstrated that γ-ionizing radiation (IR) triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9 and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression, followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

Robotic arms are increasingly being utilized in shared workspaces, which necessitates the accurate interpretation of human intentions for both efficiency and safety. Electroencephalogram (EEG) signals, commonly employed to measure brain activity, offer a direct communication channel between humans and robotic arms. However, the ambiguous and unstable characteristics of EEG signals, coupled with their widespread distribution, make it challenging to collect sufficient data and hinder the calibration performance for new signals, thereby reducing the reliability of EEG-based applications. To address these issues, this study proposes an iteratively calibratable network aimed at enhancing the reliability and efficiency of EEG-based robotic arm control systems. The proposed method integrates feature inputs with network expansion techniques. This integration allows a network trained on an extensive initial dataset to adapt effectively to new users during calibration. Additionally, our approach combines motor imagery and speech imagery datasets to increase not only its intuitiveness but also the number of command classes. The evaluation is conducted in a pseudo-online manner, with a robotic arm operating in real-time to collect data, which is then analyzed offline. The evaluation results demonstrated that the proposed method outperformed the comparison group in 10 sessions and demonstrated competitive results when the two paradigms were combined. Therefore, it was confirmed that the network can be calibrated and personalized using only the new data from new users.

It is important to operate devices with control panels and touch screens assisted by haptic feedback in mobile environments such as driving automobiles and electric power wheelchairs. A lot of consideration is needed to give accurate haptic feedback, especially, presenting clear touch feedback to the elderly and people with reduced sensation is a very critical issue from healthcare and safety perspectives. In this study, we aimed to identify the perceptual characteristics for the frequency and direction of haptic vibration on the touch screen with vehicle-driving vibration and to propose an efficient haptic system based on these characteristics. As a result, we demonstrated that the detection threshold shift decreased at frequencies above 210 Hz due to the contact pressure during active touch, but the detection threshold shift increased at below 210 Hz. We found that the detection thresholds were 0.30–0.45 gpeak with similar sensitivity in the 80–270 Hz range. The haptic system implemented by reflecting the experimental results achieved characteristics suitable for use scenarios in automobiles. Ultimately, it could provide practical guidelines for the development of touch screens to give accurate touch feedback in the real-world environment.