Fucoxanthin Abrogates Ionizing Radiation-Induced Inflammatory Responses by Modulating Sirtuin 1 in Macrophages.

Ionizing radiation (IR) triggers an overproduction of reactive oxygen species (ROS), disrupting the normal function of both immune and metabolic systems, leading to inflammation and metabolic disturbances. To address the pressing requirement for protection against IR, fucoxanthin (FX), a naturally occurring compound extracted from algae, was utilized as an efficient radioprotective agent in macrophages. In this study, we cultured murine RAW 264.7 macrophages and treated them with FX, along with agents influencing the activity of sirtuin 1 (SIRT1) and estrogen receptor α (ERα), to investigate their impact on IR-induced cellular responses. FX significantly attenuated IR-induced upregulation of pro-inflammatory genes (Il1b, Tnf, and Ccl2) and inhibited macrophage polarization toward the pro-inflammatory M1 phenotype. Additionally, FX regulated IR-induced metabolic genes mediating glycolysis and mitochondrial biogenesis. The ability of FX to mitigate IR-induced inflammation and glycolysis was ascribed to the expression and activity of SIRT1 and ERα in macrophages. This study not only uncovers the underlying mechanisms of FX's radioprotective properties but also highlights its potential as a protective agent against the detrimental effects of IR, thus offering new opportunities for enhancing radiation protection in the future.

Assessment of portal image resolution improvement using an external aluminum target and polystyrene electron filter.

BACKGROUND: In this study, an external 8 mm thick aluminum target was installed on the upper accessory tray mount of a medical linear accelerator head. The purpose of this study was to determine the effects of the external aluminum target beam (Al-target beam) on the portal image quality by analyzing the spatial and contrast resolutions. In addition, the image resolutions with the Al-target beams were compared with those of conventional 6 megavoltage (MV) images. METHODS: The optimized Al-target beam was calculated using Monte Carlo simulations. To validate the simulations, the percentage depth dose and lateral profiles were measured and compared with the modeled dose distributions. A PTW resolution phantom was used for imaging to assess the image resolution. The spatial resolution was quantified by determining the modulation transfer function. The contrast resolution was determined by a fine contrast difference between the 27 measurement areas. The spatial and contrast resolutions were compared with the those of conventional portal images. RESULTS: The measured and calculated percentage depth dose of the Al-target beam were consistent within 1.6%. The correspondence of measured and modelled profiles was evaluated by gamma analysis (3%, 3 mm) and all gamma values inside the field were less than one. The critical spatial frequencies (f50) of the images obtained with the Al-target beam and conventional imaging beam were 0.745 lp/mm and 0.451 lp/mm, respectively. The limiting spatial frequencies (f10) for the Al-target beam image and the conventional portal image were 2.39 lp/mm and 1.82 lp/mm, respectively. The Al-target beam resolved the smaller and lower contrast objects better than that of the MV photon beam. CONCLUSION: The Al-target beams generated by the simple target installation method provided better spatial and contrast resolutions than those of the conventional 6 MV imaging beam.

Establishment of an Uncomplicated Radiation-delayed Wound Healing Model Using Irradiation in Pigs.

INTRODUCTION: Radiation-delayed wounds require diverse therapeutic strategies to achieve effective healing. However, the development of novel therapies with a radiation-delayed wound healing model is hindered by the lack of standardized animal models. OBJECTIVE: In this study, the authors propose and verify a procedure to establish a radiation-delayed wound healing model in pigs. MATERIALS AND METHODS: Two female pigs received a single 18-Gy dose of a 6-MeV electron beam per 18 cm x 8 cm area. Three areas were treated on the paraspinal dorsal skin surface of each pig, with 2 on the left side of the spine and 1 on the right. Wounds were periodically created on the 2 pigs at 1 of the following time points: (1) 2 weeks post radiation (PR2 group; n = 4), (2) 4 weeks post radiation (PR4 group; n = 4), and (3) 6 weeks post radiation (PR6 group; n = 4). A partial-thickness wound was created by excising the skin, superficial fat layer, and superficial fascia while preserving the deep fat and deep fascia. Wound contraction was evaluated, and histological analysis was performed at 2 and 4 weeks after wounding. RESULTS: The control wounds displayed complete reepithelialization at week 4. However, the PR6 group showed delayed wound healing for the entire experimental period. Furthermore, compared with the control group, the PR6 group demonstrated excessive acute and chronic inflammation and exhibited incomplete reepithelialization at week 4. CONCLUSIONS: These findings suggest skin wounding 6 weeks after irradiation is most suitable for the induction of a delayed wound healing model. Using this protocol, the authors safely generated a delayed wound healing model without acute complications from irradiation.

Investigation of the use of external aluminium targets for portal imaging in a medical accelerator using Geant4 Monte Carlo simulation.

OBJECTIVE: To install a low-Z target on the wedge tray mount of a medical linear accelerator to create a new image beam and to confirm image contrast enhancement. METHODS: Experimental low-energy photon beams were produced with the linac running in the 6 MeV electron mode and with a low-Z target installed on the wedge tray mount [denoted 6 MeV (low-Z target)]. Geant4 Monte Carlo simulation was performed to analyse the energy spectrum and image contrast of a 6 MeV (low-Z target) beam. This study modelled the 6 MeV (low-Z target) beam and the 6 MV (megavoltage) radiotherapy photon beam and verified model validity by measurement. In addition, a contrast phantom was modelled to quantitatively compare the image contrasts of the 6 MeV (low-Z target) beam and the 6 MV radiotherapy photon beam. A low-Z target was fabricated to generate low-energy photons (25-150 keV) from incident electrons, and a portal image of the Alderson RANDO phantom was acquired using a clinical linear accelerator for qualitative analysis. RESULTS: The measured and calculated percentage depth dose of the 6 MV photon and 6 MeV (Al) beams were consistent within 1.5 and 1.6%, respectively, and calculated lateral profiles of the 6 MV photon beam and the 6 MeV (Al) beam were consistent with the measured results within 1.5 and 1.9%, respectively. Although low-energy photons (25-150 keV) of the 6 MV photon beam were only 0.3%, the Be, C, and Al low-Z targets, but not the Ti target, generated 34.4 to 38.5% low-energy photons. In 5 to 20 cm water phantoms, contrast of the 6 MeV (Al) beam was approximately 1.16 times greater than that of the 6 MV beam. The contrasts of 6 MeV (Al) and 6 MV photon beams in the 20 cm water phantom were ~34% lower than those in the 5 cm water phantom. 6 MeV (Al)/CR (computed radiography) images of the human body phantom were more vivid and detailed than 6 MV/EPID (electronic portal imaging device) and 6 MeV (Al)/EPID images. CONCLUSION: The experimental beam with a low-Z target, which was simply installed on the wedge tray mount of the radiotherapy linear accelerator, generated significantly more low-energy photons than the 6 MV radiotherapy photon beam, and provided better quality portal images. Advances in knowledge: This study shows that, unlike the existing low-Z beam studies, a low-Z target can be installed outside the head of a linear accelerator to improve portal image quality.

Serial changes in the proliferation and differentiation of adipose-derived stem cells after ionizing radiation.

BACKGROUND: Adipose-derived stem cells (ASCs) are important to homeostasis and the regeneration of subcutaneous fat. Hence, we examined the proliferation and differentiation capacity of irradiated ASCs over time. METHODS: Two female pigs received a single 18 Gy dose of ionizing radiation to an 18 × 8 cm area on the dorsal body skin via a 6 MeV electron beam. After irradiation, the ASCs were cultured from adipose tissue harvested from a non-irradiated area and an irradiated area at 2, 4, and 6 weeks. The proliferation capacity of ASCs was evaluated by a colony-forming units-fibroblasts (CFUs-Fs) assay, a cholecystokinin (CCK) test with 10 % fetal bovine serum (FBS), and a 1 % FBS culture test. The senescence of ASCs was evaluated through morphological examination, immunophenotyping, and ß-galactosidase activity, and the multipotent differentiation potential of ASCs was evaluated in adipogenic, osteogenic, and chondrogenic differentiation media. RESULTS: Irradiated ASCs demonstrated significantly decreased proliferative capacity 6 weeks after irradiation. As well, the cells underwent senescence, which was confirmed by blunted morphology, weak mesenchymal cell surface marker expression, and elevated ß-galactosidase activity. Irradiated ASCs also exhibited significant losses in the capacity for adipocyte and chondrocyte differentiation. In contrast, osteogenic differentiation was preserved in irradiated ASCs. CONCLUSIONS: We observed decreased proliferation and senescence of irradiated ASCs compared to non-irradiated ASCs 6 weeks after irradiation. Furthermore, irradiated ASCs demonstrated impaired adipocyte and chondrocyte differentiation but retained their osteogenic differentiation capacity. Our results could shed light on additional pathogenic effects of late irradiation, including subcutaneous fibrosis and calcinosis.

Assessment of setup uncertainties for various tumor sites when using daily CBCT for more than 2200 VMAT treatments.

The aim of this study was assess the patient setup errors for various tumor sites based on clinical data from a sufficient number of treatments with volumetric-modulated arc therapy (VMAT) using daily pretreatment CBCT imaging guidance. In addition, we calculated and compared the planning target volume (PTV) margins for all disease sites based on an analysis of specific systematic and random errors in our institution. All patients underwent pretreatment kV-CBCT imaging. The various tumor sites were divided into four categories; 21 brain (438 fractions), 35 head-and-neck tumors (H&N, 933 fractions), 19 thorax and abdomen tumors (T&A, 313 fractions), and 17 prostate cancer tumors (546 fractions). Overall distributions of setup corrections in all directions, frequencies of 3D vector lengths, institution-specific setup error, and PTV margins were analyzed. The longitudinal distribution for the T&A site represented an asymmetric offset in the negative direction. Rotational distributions were comparable for all treatment sites, and the prostate site had the narrowest distribution of ≤ ± 2°. The cumulative frequencies of 3D vector length of ≥ 7 mm were rare for brain lesions and H&N, but more common for T&A and prostate lesions at 25.6% and 12.1%, respectively. The overall mean error for all treatment sites were within ± 1 mm and ± 0.1°, with the exception of the T&A site, which had overall mean error of 2 mm in the negative longitudinal direction. The largest magnitude of systematic error and random error for the brain lesions and H&N was 1.4 mm in the translational directions, and 3.3 mm for T&A and prostate lesions. The PTV margins required in this analysis are ≤ 4 mm for the brain lesions and H&N in all translational directions, but ranged from 4 to 10 mm for T&A and prostate lesions. Analysis of each institution's specific setup errors using daily CBCT is essential for determining PTV margins and reducing setup uncertainties, because setup errors vary according to each immobilization system and patient.