BACKGROUND: Hyperthermia (HT), while a cancer treatment approach, isn't always effective alone. Therefore, identifying hyperthermia enhancers is crucial. We demonstrated that Mito-TEMPO ([2-[(1-Hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) amino]-2-oxoethyl]-triphenylphosphanium, MT) acts as a potent thermosensitizer, promoting cell death in human cervical cancer (HeLa) cells. METHODS: Cells were pretreated with 0.4 mM MT for 5 minutes, followed by exposure to hyperthermia (42 °C for 60 minutes). The impacts of MT/HT on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, apoptosis-related proteins and autophagy, autophagy-related proteins expression were measured. The relationships between autophagy and apoptosis were further investigated using the specific autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (Rapa). RESULTS: The combined treatment reduced the mitochondrial membrane potential (MMP) and increased ROS production. It also upregulated the pro-apoptotic protein Bax and downregulated anti-apoptotic proteins such as Bcl-2 and MCL-1. As a result, Caspase-3 was activated. Additionally, the combined treatment upregulated the expression of p-PERK/PERK, ATF-4, CHOP proteins. Moreover, the combined treatment also increased the expression of LC3 II and p62, decreased expression of LAMP 1 and Cathepsin D and increased lysosomal pH, indicating coordinated changes in autophagy regulation. Notably, intensification of apoptosis induced by the combined treatment was observed with CQ, whereas attenuation was seen with Rapa. CONCLUSIONS MT effectively enhanced HT-induced apoptosis in HeLa cells. Elevated ER stress and interruption of autophagy flux are the possible underlying molecular mechanisms for this phenomenon. These findings suggested MT can act as a potential thermosensitizer, highlighting its versatility in cancer treatment strategies.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; HeLa Cells ; Uterine Cervical Neoplasms/therapy* ; Female ; Hyperthermia, Induced ; Spin Labels ; Endoplasmic Reticulum Stress/drug effects* ; Cyclic N-Oxides/pharmacology* ; Cell Survival/drug effects*

Purpose：We investigated the factors associated with medical device-related pressure ulcer (MDRPU) due to lower extremity orthosis in patients undergoing convalescent rehabilitation for stroke.Methods：This retrospective study included patients with stroke who wore ankle foot orthosis in the convalescent rehabilitation ward. We measured the following items at admission：Brunnstrom recovery stage, presence of sensory disturbance, exhibition of unilateral spatial neglect, functional independence measures at admission and discharge, and presence of MDRPU. In the statistical analysis, logistic regression analysis was performed to identify the significant factors associated with MDRPU.Results：Ninety-five participants were enrolled in this study (mean age：54.9 ± 11.6 years, Male：78.9%). In logistic regression analysis, Age (odds ratio＝1.05, 95% confidence interval＝1.01-1.10, p＜0.05) and the presence of sensory disturbance (odds ratio＝5.17, 95% confidence interval＝1.39-19.28, p＜0.05) at admission was extracted as the cause of MDRPU.Conclusion：Sensory disturbance at admission is associated with MDRPU in patients undergoing convalescent rehabilitation for stroke who wear ankle foot orthosis.