International journal of radiation biology最新文献

Purpose: Magnetic resonance (MR)-guided radiotherapy (MRgRT) is an attractive treatment option for many patients with cancer, allowing higher radiation doses to be safely delivered. However, even with more precise tumor targeting and higher doses, hypoxia remains an important clinical challenge, making tumors more radioresistant and detracting from the benefits of dose escalation. Nanoparticles loaded with manganese dioxide (MnO₂) have been developed as theranostic agents to improve MRgRT. We review the MR-enhancing and oxygen-generating properties of MnO₂ nanoparticles, the evidence that MnO₂ nanoparticles can improve tumor response to RT, and the opportunities for further research to support translation into the clinic.

Conclusion: The theranostic potential of MnO₂ nanoparticles lies in the dual functionality of providing tumor-specific MR enhancement for RT planning and image guidance, while also generating oxygen in the tumor microenvironment (TME) to overcome hypoxia-induced radioresistance. Several preclinical studies have demonstrated lower levels of hypoxia and improved tumor response when RT is combined with MnO₂ nanoparticles. In addition, MnO₂ nanoparticles have been reported to deplete intracellular antioxidants and create an immunogenic, less immunosuppressive TME, which may also enhance radiotherapy efficacy. These encouraging findings support further clinical evaluation in patients receiving MRgRT.

Purpose: Radiotherapy (RT) is a key treatment for localized prostate cancer (PCa); however, resistance and recurrence remain major challenges. Hyaluronan (HA), a key component of the extracellular matrix, has been implicated in cancer progression and therapeutic resistance. However, its role in the modulation of radiosensitivity, particularly in the tumor microenvironment, remains unclear. In this study, we aimed to investigate the role of HA in the radiosensitivity of PCa cells.

Materials and methods: 22Rv1 PCa epithelial cells and WPMY-1 myofibroblast cells were cultured to mimic tumor-stroma interactions. The effect on radiosensitivity was evaluated using colony formation assays. HA levels and molecular weight from cell culture supernatants were analyzed using enzyme-linked immunosorbent assays and agarose gel electrophoresis. Hyaluronidase expression was assessed using quantitative RT-PCR.

Results: WPMY-1 cells exposed to supernatants had significantly higher HA secretion than 22Rv1 cells. WPMY-1-derived HA enhanced the radioresistance of 22Rv1 cells, which was reversed by hyaluronidase. HA induced by 22Rv1-derived factors appears to be necessary for colony formation. The induced HA showed a shift toward a higher molecular weight owing to the downregulation of the degrading enzymes Hyal1 and PH20. The molecular weight of HA played a key role in modulating these effects.

Conclusion: Our findings suggest that stromal cells may contribute to the radioresistant tumor microenvironment in PCa partly through alterations in high-molecular-weight HA. While targeting HA metabolism holds potential to improve the efficacy of RT by disrupting this protective niche, further studies are needed to clarify the underlying mechanisms and validate these effects in vivo.

Objective: This position paper results from an International Union of Radioecology symposium aimed at identifying challenges to develop eco-centric and holistic approaches to understanding ionizing radiation impacts on ecosystems. An ecosystem approach is particularly relevant today not only because of the triple planetary crisis of climate change, biodiversity loss, and pollution, which make single-stressor approaches unrealistic, but because of renewed interest in nuclear power as a potential solution to transition away from fossil fuels. For example, there are proposals to site small modular reactors in remote and pristine areas. The focus of the symposium was to expand the boundaries of existing approaches in radioecology and look at issues like ecosystem complexity and multiple stressors, which complicate single-stressor approaches.

Conclusions: Discussion centered around existing tools for radiation protection e.g. Adverse Outcome Pathway (AOP) analysis, biomarkers, use of microcosms and mesocosms and modeling approaches. These approaches were discussed with emphasis on identifying gaps, boundaries, and where leaps into the unknown might be beneficial. Identified challenges with biomarker and AOP approaches were that the individual level is generally addressed while interrelatedness of ecosystem components is difficult to capture. Novel ideas suggested were to construct multiple-stressor AOPs which capture key interactions and consider time as a critical component, or to exploit 'ecological network analysis' metrics which have been extensively used in ecological science. Other discussions centered on complexity and chaos modeling. The use of microcosms, focused field studies, and harnessing ecosystem information and communication systems were suggested to bridge the gap between individual and population-level responses.

Introduction: Radiation-induced brain injury causes significant neurotoxicity and cognitive dysfunction in patients undergoing radiotherapy for brain tumors. This study aimed to evaluate the neuroprotective effects of intranasal ketamine on radiation-induced brain injury, specifically focusing on its modulation of perineuronal networks (PNNs), extracellular matrix components, and neuroinflammation.

Materials and methods: Eighteen male New Zealand White Rabbits were divided into three groups: normal controls, irradiation (IR) with saline (IR + saline), and IR with ketamine (IR + ketamine). Whole-brain IR (20 Gy) was applied to the IR groups, and ketamine (2 mg/kg/day) was administered intranasally for 15 days. Biochemical markers, including malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), brain-derived neurotrophic factor (BDNF), ADAMTS4, and syndecan-1 levels, were measured. Histopathological analysis of hippocampal and cerebellar regions assessed neuronal survival and astrogliosis. Magnetic resonance spectroscopy (MRS) evaluated lactate and N-acetylaspartate (NAA) levels, reflecting metabolic and neuronal integrity.

Results: Ketamine administration significantly reduced oxidative stress (MDA) and inflammatory markers (TNF-α) while restoring BDNF levels compared to the IR + saline group. ADAMTS4 and syndecan-1 levels were reduced, changes consistent with PNN-associated extracellular matrix dynamics, but without direct confirmation by core PNN markers such as aggrecan or WFA staining. Histopathology showed increased neuronal survival and decreased reactive astrogliosis in ketamine-treated groups. ¹H-MRS provided supporting evidence for metabolic changes (↓lactate, ↑NAA) consistent with improved mitochondrial function and neuronal integrity.

Conclusion: Intranasal ketamine demonstrates significant neuroprotective effects in a radiation-induced brain injury model by reducing oxidative stress and inflammation, modulating extracellular matrix components, and preserving neuronal integrity. These findings highlight ketamine's potential as a therapeutic agent, although direct PNN markers and broader cytokine panels were not assessed. Overall, ketamine showed neuroprotective effects across biochemical, histological, and MRS-supported metabolic readouts.

Purpose: Radiation-induced intestinal injury (RIII) is a common complication after radiotherapy for abdominal and pelvic tumors, which seriously affects the prognosis and treatment outcome of patients, and lacks effective prevention and treatment methods. The primary pathological manifestations of RIII are the death of intestinal epithelial cells, as well as the destruction of the intestinal mechanical barrier's integrity, which is closely related to various kinds of programmed cell death (PCD). In addition, radiation-induced DNA double-strand breaks can trigger a variety of PCDs. Elucidating how different PCD pathways regulate RIII molecular mechanisms and identifying the key therapeutic targets will provide the theoretical foundation for developing RIII prevention and treatment strategies. This review systematically expounds the role of PCD in the pathogenesis of RIII and summarizes the relevant small molecule drugs currently under research.

Conclusion: PCD plays a central role in the occurrence and development of RIII. Analyzing single pathways and elucidating the 'cross-talk' and regulatory logic between different forms of PCD, as well as identifying key molecular targets located at the intersection of multiple pathways, is likely to become a more effective new direction for prevention and treatment.

Purpose: Low-dose-rate (LDR) radiation is known to induce subtle biological effects, but its impact on body fluid-based biomarkers remains poorly defined. This study evaluated dose rate-dependent hematological, biochemical, and immunological changes in blood, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) in healthy mice.

Materials and methods: Mice were exposed to whole-body LDR radiation at 0.39, 1.29, or 3.46 mGy/h for 21 days. Hematological analysis was performed on blood, and PLF and BALF were analyzed for biochemical and immune cell parameters.

Results: Most hematological indices were stable, except in the 3.46 mGy/h group, which showed significant changes in reticulocytes, white blood cells, lymphocytes, and platelet-large cell ratio. In PLF, alkaline phosphatase isoenzyme fraction (ALPIF) increased at 0.39 mGy/h, while AST, CK, and lactate were elevated at 1.29 mGy/h but normalized at 3.46 mGy/h. Immune analysis revealed increased polymorphonuclear cells and reduced lymphocytes in PLF at 0.39 mGy/h, indicating localized immune activation. In contrast, BALF showed no significant biochemical or cellular changes. A cross-compartment comparison of ALT, AST, and CK revealed hepatic or muscular stress in blood at 0.39 mGy/h, and localized metabolic alterations in PLF at 1.29 mGy/h.

Conclusions: LDR radiation induces non-linear, dose rate-specific effects on immune and metabolic parameters in blood and PLF, while BALF responses remain minimal. These findings highlight the utility of fluid-based biomarkers for early, minimally invasive detection of radiation-induced changes.

Purpose: High linear energy transfer (LET) radiation is more harmful than low LET radiation because it deposits energy in a concentrated manner, resulting in clustered DNA damage (CDD). Double strand breaks (DSBs) are among the most damaging types of DNA damage, and if not repaired, they may trigger cell death. DSBs can be repaired through three mechanisms: non-homologous end joining (NHEJ), homologous recombination (HR), and theta-mediated end joining (TMEJ). This study aimed to assess how these pathways contribute to repairing DSBs induced by low LET X-ray and proton radiation, and high LET alpha-particle radiation.

Materials and methods: We used mouse embryonic stem (mES) cells lacking key repair proteins to examine clonogenic survival and the formation and resolution of 53BP1 foci, a DNA damage marker, after exposure to X-ray, proton, and alpha-particle radiation.

Results and conclusions: The results showed increased sensitivity to X-ray and proton radiation in NHEJ, HR, and TMEJ repair-deficient cell lines compared to wild-type cells, with similar trends for both radiation types. Notably, Rad54-deficient cells showed slower resolution of 53BP1 foci after proton exposure, indicating increased reliance on HR for repairing proton-induced DSBs. Clonogenic survival assays revealed a relative biological effectiveness (RBE) of 4.6-5.8 for alpha-particles compared to protons and X-rays, confirming that alpha-particles are more effective at causing cell death. Our findings suggest that TMEJ is important for repairing DSBs caused by alpha-particles. This study highlights differences in repairing low LET versus high LET DNA damage, offering new insights for radiation biology and therapeutic strategies.

Purpose: Accurate dose estimation is crucial in radiation emergency medicine to predict potential clinical outcomes and to develop appropriate treatment plans. This need becomes especially important during mass-casualty events, where reliable and rapid triage is necessary. However, cytogenetic biodosimetry, which can be used for triage, is bottlenecked by the time required for cell culture and the expertise needed of chromosomal analysis. The objective of this study is to apply deep learning-based object detection to the analysis of micronuclei (MNs).

Materials and methods: Peripheral blood samples were collected from healthy volunteers with informed consent. For model training and validation, samples were irradiated at 0 (sham), 2, and 3 Gy. Whole blood cultures were stimulated with phytohemagglutinin and treated with cytochalasin B (at 44 h) for 72 h. Cells were scanned for whole slide imaging. M1-M4 cells were annotated for nuclear division index (NDI) analysis, and main nuclei and MNs in binucleated cells (M2) were annotated for MNs analysis. Both the NDI and MNs models were trained using the YOLOv5 framework. Dose-response curves generated by the deep learning-based models were compared with previously published manually scored curves.

Results: Although still in the preliminary stages, we confirmed that deep learning-based object detection using YOLOv5 can achieve good classification performance. There is a possibility for further improvement of the model using data augmentation, particularly for a low number of training images. The dose-response curves derived from deep learning-based analysis were comparable to previously reported manual calibration curves.

Conclusion: The use of deep learning techniques for image recognition offers a promising approach for rapid and reliable NDI and MNs detection in cytogenetic biodosimetry.

Purpose: Performing biodosimetry assessment for several hundreds of thousands of individuals in the aftermath of large scale radiological/nuclear incidents will be technically challenging. The purpose of this review is to provide logistical planning to determine when, how and which biodosimetry tools can be used for providing useful information to mediate an effective triage and for guiding the medical management of exposed victims of such an event. Conclusions: This review highlighted the potential capabilities of various types of biodosimetry tools in advanced development to handle the needs of different triage stages for a large-scale nuclear detonation event. While each was reviewed independently, the consensus was that complex exposure scenarios require a multiparametric approach where biomarkers/biodosimeters can be used alternatively or targeted for subgroups, e.g. with combined injury or by type of radiation, for rapid assessment and confirmation of exposure dose for exposed individuals. Further studies and exercises are required to validate the capability of using the biodosimetry tools, both individually and in combination, under the likely logistical constraints of a nuclear detonation, both to guide development of processes such as high-throughput platforms and field-deployable mechanisms that can best address the volume and needs of the affected population.

Purpose: This study aimed to optimize the preparation conditions and compare the UVB protection efficacy of three lipid-based nanocarrier formulations encapsulating enriched astaxanthin extract (ATXex) derived from Haematococcus pluvialis.

Materials and methods: The lipid-based nanocarriers encapsulating ATXex (Nano-ATXex) included nanoliposomes (NL), nanoemulsions (NE), and nanostructured lipid carriers (NLC). The formulations were prepared using a combination of ultrasonication and high-shear homogenization (for NE-ATXex), hot homogenization (for NLC-ATXex), or thin-film hydration (for NL-ATXex). Key parameters were evaluated to determine optimized preparation conditions, including surfactant ratios, lipid-to-surfactant ratios, and dispersion phase concentrations. The biological activities of the optimized Nano-ATXex formulations were evaluated using ABTS, MTT, γ-H2AX, and β-galactosidase assays, with in vivo UVB protection assessed in a murine model.

Results: All three Nano-ATXex formulations exhibited negative surface charge, spherical morphology, mean particle size of approximately 110 nm, PDI around 0.2, and high encapsulation efficiency exceeding 85%. The ABTS radical scavenging efficiency of Nano-ATXex was significantly higher than that of Trolox. Cytotoxicity was dependent on the lipid-based nanocarrier formulation and the concentration of ATXex. Biological activity evaluations demonstrated that NLC-ATXex significantly reduced the number of γ-H2AX foci per nucleus and the proportion of β-galactosidase-positive cells and mitigated UVB-induced skin damage more effectively than NE-ATXex and NL-ATXex.

Conclusions: Three successfully optimized Nano-ATXex formulations protected against UVB-induced DNA damage and senescence in vitro and alleviated skin damage in vivo, with NLC-ATXex showing the highest efficacy. The differences in cytocompatibility and biological activities indicated the importance of selecting an appropriate lipid-based nanocarrier formulation. These findings support the potential of ATXex-loaded nanocarriers in skin protection applications.