Eun Ho Kim

Osteosarcoma (OS) is the most common type of bone cancer and is highly resistant to conventional photon beam radiotherapy; however, carbon-ion radiotherapy (CIRT) is effective in treating OS. In this study, to investigate whether miR-17-5p/miR-17-3p inhibitors act as radiosensitizers for CIRT, U2OS and MG63 OS cells were treated with carbon-ion beam irradiation (IR) alone, X-ray IR alone, or with one of the IR treatments in combination with miR-17-3p inhibitors. Cell death and invasive and migratory abilities were analyzed using cell viability and cell Transwell migration and invasion assays. Apoptosis and autophagy-related protein expression and DNA double-strand break (DSB) induction was determined using western blotting and immunofluorescence staining. We found that carbon-ion beam IR combined with miR-17-5p/miR-17-3p inhibitors significantly inhibited OS cell proliferation, migration, and invasion and markedly increased apoptosis-related cleaved-caspase 3, cleaved-PARP expression compared to carbon-ion beam IR and X-ray IR alone. Furthermore, carbon-ion beam IR combined with miR-17-5p/miR-17-3p inhibitors markedly promoted autophagy induction. In addition, combination treatment with miR-17-5p/miR-17-3p inhibitors and carbon-ion beam IR significantly increased the number of γH2AX foci as well as its phosphorylation. Taken together, miR-17-5p/miR-17-3p inhibitors enhanced the carbon-ion beam radiosensitivity of OS cells, presenting a novel strategy for the development of carbon-ion beam combination therapy.

Kim EH, et al. Brain Neurorehabil. 2026 ;19:e3. https://doi.org/10.12786/bn.2026.19.e3

Background: Proton-boron capture therapy (PBCT) has been proposed as a method to enhance the biological effectiveness of proton therapy through the p + ¹¹ B → 3α nuclear reaction. The resulting alpha particles may increase local radiation quality, but the dosimetric and microdosimetric consequences remain uncertain. Methods: Lineal energy distributions were measured using a Silicon-On-Insulator (SOI) microdosimeter under 70 MeV and 190 MeV monoenergetic proton beams delivered with pencil beam scanning. Dose-averaged lineal energy ( y D ¯ ) values were derived from oscilloscope signals calibrated against Geant4 Monte Carlo simulations. Measurements were performed at both entrance and Bragg peak depths, with and without boronophenylalanine (BPA) delivered via EnGeneIC Dream Vector (EDV™). In parallel, a treatment planning study was conducted in Eclipse TPS to assess the impact of localized high-density boron regions on dose distributions under conventional and FLASH-simulated delivery, using both fixed and variable RBE models. Results: For 70 MeV protons, no significant difference in y D ¯ was observed between boron-loaded and control conditions. At 190 MeV, a reproducible increase in y D ¯ was detected at the Bragg peak in the presence of boron (p < 0.01), while no effect was observed at the entrance depth. Treatment planning simulations showed that localized boron density improved dose uniformity within the clinical target volume and reduced discrepancies between fixed and variable RBE dose distributions under FLASH conditions. Discussion: These findings indicate that PBCT can induce detectable increases in microdosimetric lineal energy under high-energy proton beams, even in the absence of macroscopic dose enhancement. The treatment planning results further highlight the potential of boron-enhanced LET modulation in conjunction with FLASH delivery. Together, the study supports continued investigation of PBCT as a strategy to optimize biological effectiveness in proton therapy, with future work focusing on realistic boron distribution models and integration of dose-rate effects.

Insoluble iron deposits often exist as iron oxide nanoparticles in protein aggregates, impaired ferritin, or activated microglia and have been implicated as major causes of neuroinflammation in Alzheimer’s disease. However, no crucial evidence has been reported to support the therapeutic effects of current iron chelators on the deposition of various molecular forms of insoluble iron. We investigated the therapeutic effect of carbon ion stimulation (CIS) via a transmission beam on insoluble iron deposits, iron inclusion bodies, and the associated biological response in 5xFAD AD mouse brains. Compared with no treatment, CIS dose-dependently induced a 33–60% reduction in the amount of ferrous-containing iron species and associated inclusion bodies in the brains of AD mice. CIS induced considerable neuroinflammation downregulation and, conversely, anti-inflammatory upregulation, which was associated with improved memory and enhanced hippocampal neurogenesis. In conclusion, our results suggest that the effective degradation of insoluble iron deposits in combination with pathogenic inclusion bodies promotes AD-modifying properties and offers a potential CIS treatment option for AD.

Alzheimer’s disease (AD) presents a significant challenge due to its multifaceted nature, characterized by cognitive decline, memory loss, and neuroinflammation. Though AD is an extensively researched topic, effective pharmacological interventions remain elusive, prompting explorations into non-pharmacological approaches. Microcurrent (MC) therapy, which utilizes imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates the impact of MC on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and the preservation of the neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. This study determined that glial activation is effectively reduced by using MC therapy to suppress the TLR4-MyD88-NFκB pathway, which consequently causes the levels of inflammatory factors TNF-α, IL-1β, and IL-6 to decrease, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, a further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.

Alzheimer's Disease (AD) presents a significant challenge in the wake of its multifaceted nature, characterized by cognitive decline, memory impairment, and neuroinflammation. Despite extensive research, effective pharmacological interventions remain elusive, prompting exploration into non-pharmacological approaches. Microcurrent therapy (MC), utilizing imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates its impact on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and preservation of neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. Our study discovered that MC therapy effectively reduces glial activation by inhibiting the TLR4-MyD88-NFκB pathway, consequently leading to decreased levels of inflammatory factors TNF-α, IL-1β, and IL-6, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.

This study primarily aimed to investigate the combined effects of polydeoxyribonucleotide (PDRN) and extracorporeal shock wave therapy (ESWT) sequences on the regenerative processes in atrophied animal muscles. Thirty male New Zealand rabbits, aged 12 weeks, were divided into five groups: normal saline (Group 1), PDRN (Group 2), ESWT (Group 3), PDRN injection before ESWT (Group 4), and PDRN injection after ESWT (Group 5). After 2 weeks of cast immobilization, the respective treatments were administered to the atrophied calf muscles. Radial ESWT was performed twice weekly. Calf circumference, tibial nerve compound muscle action potential (CMAP), and gastrocnemius (GCM) muscle thickness after 2 weeks of treatment were evaluated. Histological and immunohistochemical staining, as well as Western blot analysis, were conducted 2 weeks post-treatment. Staining intensity and extent were assessed using semi-quantitative scores. Groups 4 and 5 demonstrated significantly greater calf muscle circumference, GCM muscle thickness, tibial nerve CMAP, and GCM muscle fiber cross-sectional area (type I, type II, and total) than the remaining three groups (p < 0.05), while they did not differ significantly in these parameters. Groups 2 and 3 showed higher values for all the mentioned parameters than Group 1 (p < 0.05). Group 4 had the greatest ratio of vascular endothelial growth factor (VEGF) to platelet endothelial cell adhesion molecule-1 (PECAM-1) in the GCM muscle fibers compared to the other four groups (p < 0.05). Western blot analysis revealed significantly higher expression of angiogenesis cytokines in Groups 4 and 5 than in the other groups (p < 0.05). The combination of ESWT and PDRN injection demonstrated superior regenerative efficacy for atrophied calf muscle tissue in rabbit models compared to these techniques alone or saline. In particular, administering ESWT after PDRN injection yielded the most favorable outcomes in specific parameters.

Objective: The main purpose of the study is to investigate the combined effects of polydeoxyribonucleotide (PDRN) and extracorporeal shock wave therapy (ESWT) sequences on the regenerative processes in atrophied animal muscles. Methods: Thirty male New Zealand rabbits, aged 12 weeks, were divided into five groups: normal saline, PDRN, ESWT, PDRN injection before ESWT, and PDRN injection after ESWT. Following 2 weeks of cast immobilization, the respective treatments were administered to the atrophied calf muscles. Radial ESWT was performed twice weekly. The evaluation included measurements of calf circumference, tibial nerve compound muscle action potential (CMAP), and gastrocnemius (GCM) muscle thickness after 2 weeks of treatment. Histological and immunohistochemical staining, as well as Western blot analysis, were conducted 2 weeks post-treatment. Staining intensity and extent were assessed using semi-quantitative scores. Results: Groups 4 and 5 demonstrated significantly greater calf muscle circumference, GCM muscle thickness, tibial nerve CMAP, and GCM muscle fiber cross-sectional area (types I, II, and total) than in the remaining three groups (p < 0.05), while they did not did not differ significantly in these parameters. Groups 2 and 3 showed the higher values for all the observations compared to group 1 (p < 0.05). Group 4 had the greatest ratio of vascular endothelial growth factor (VEGF) to platelet endothelial cell adhesion molecule-1 (PECAM-1) in the gastrocnemius muscle fibers than in the other four groups (p < 0.05). Western blot analysis revealed significantly higher expression of angiogenesis cytokines in groups 4 and 5 than in the remaining (p < 0.05). Conclusion: The combination of ESWT and PDRN injection demonstrated superior regenerative efficacy for atrophied calf muscle tissue in rabbit models than these techniques alone or saline. Particularly, administering ESWT after PDRN injection yielded the most favorable outcomes in specific parameters.

Liposarcoma (LPS) is a rare type of soft tissue sarcoma that constitutes 20% of all sarcoma cases in adults. Effective therapeutic protocols for human LPS are not well‑defined. Tumor‑treating fields (TTFields) are a novel and upcoming field for antitumor therapy. TTFields combined with chemoradiotherapy have proven to be more effective than TTFields combined with radiotherapy or chemotherapy alone. The present study aimed to assess the effectiveness of TTFields in inhibiting cell proliferation and viability for the anticancer treatment of LPS. The present study used TTFields (frequency, 150 kHz; intensity, 1.0 V/cm) to treat two LPS cell lines (94T778 and SW872) and analyzed the antitumor effects. According to trypan blue and MTT assay results, TTFields markedly reduced the viability and proliferation of LPS cell lines along with the formation of colonies in three‑dimensional culture. Based on the Transwell chamber assay, TTFields treatment also markedly reduced the migration of LPS cells. Furthermore, as shown by the higher activation of caspase‑3 in the Caspase‑3 activity assay and the results of the reactive oxygen species (ROS) assay, TTFields increased the formation of ROS in the cells and enhanced the proportion of apoptotic cells. The present study also investigated the inhibitory effect of TTFields in combination with doxorubicin (DOX) on the migratory capacity of tumor cells. The results demonstrated that TTFields treatment synergistically induced the ROS‑induced apoptosis of LPS cancer cell lines and inhibited their migratory behavior. In conclusion, the present study demonstrated the potential of TTFields in improving the sensitivity of LPS cancer cells, which may lay the foundation for future clinical trials of this combination treatment strategy.