Radiation research最新文献

{"title":"A Murine Model of Radionuclide Lung Contamination for the Evaluation of Americium Decorporation Treatments.","authors":"Trevor Arino, Alexia G Cosby, Jennifer Alvarenga-Vasquez, Kirsten E Martin, Alex Rigby, Adrianna Reece-Newman, Shereen Aissi, Ethan Hallick, Isaac Jaro, Rebecca J Abergel","doi":"10.1667/RADE-25-00001.1","DOIUrl":"10.1667/RADE-25-00001.1","url":null,"abstract":"<p><p>The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) (HOPO), has been previously characterized as a promising chelating agent for in vivo decorporation of actinides, with decorporation being the removal of internally deposited contaminants from the body after exposure. The large majority of relevant literature reports have detailed the efficacy profile of HOPO as a decorporation agent in rodent models, where controlled radionuclide contamination is conducted via intravenous injection. However, this method of contamination does not necessarily reflect an accurate predictive model of the most probable biodistribution of free metal in the body. In the event of a radiological dispersal device or nuclear power plant accident scenario, it is most likely that first responders, military personnel, and victims of the event will be contaminated via air and water transmission. Therefore, research into the efficacy of chelating agents to treat lung-contaminated in vivo models needs to be carried out. Here, we establish a murine model with controlled, reproducible lung contamination using two different radionuclides, 89Zr and 241Am, for orthogonal biodistribution validation by positron emission tomography and ex vivo radioanalysis, respectively. In addition, we report effective chelation treatment of 241Am-contaminated lungs using HOPO, which improves decorporation by up to 40% compared to Ca-DTPA, the current standard of care.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"389-397"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Octamer-Binding Transcription Factor 4 Inhibits HSC Functions via the NF-κB Signaling Pathway After 60Co Irradiation.","authors":"Wenjing Yang, Xiaoe Jin, Chao Chen, Qianqian Zhang, Junyang Wang, Jinjia Liu, Lina Song, Xiaolong Jiang, Yunjian Liu, Weihong Li, Shufang Cui","doi":"10.1667/RADE-24-00258.1","DOIUrl":"10.1667/RADE-24-00258.1","url":null,"abstract":"<p><p>High doses of radiation can cause irreversible bone marrow hematopoietic damage and even death. No effective strategies have been developed to protect against radiation effects in hematopoietic stem cells (HSCs). A total-body irradiation model was used to determine damage to HSCs. HSCs were sorted for transcriptome sequencing, and gene function analysis showed that Octamer-Binding Transcription Factor 4 (Oct4) increased significantly after irradiation. Oct4 deletion or inhibition of nuclear factor kappa-B (NF-κB) significantly reversed HSC apoptosis, promoted HSC colony formation, reduced cellular DNA damage, and promoted bone marrow regeneration after irradiation. ChIP assays showed that Oct4 binds to the IκB kinase (IKK) promoter region and increases the level of IKK. Overexpression of Oct4 significantly increased the entry of NF-κB into the nucleus after irradiation. NF-κB activators reversed the protective roles of knocking out Oct4. In vivo, the knockout of Oct4 and inhibition of NF-κB significantly improved the survival rate of mice after irradiation. We further found that the expression level of Oct4 decreased significantly in human leukemia cells, while the overexpression of Oct4 significantly increased the level of apoptosis in leukemia cells after irradiation. This study demonstrated a novel role of Oct4 in mediating apoptosis of HSCs after irradiation through the NF-κB pathway, providing an important biomedical strategy for the functional protection of HSCs in bone marrow after irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"433-444"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERRATUM.","authors":"","doi":"10.1667/RADE-25-e0001.1","DOIUrl":"10.1667/RADE-25-e0001.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":"203 6","pages":"447"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between DNA Double-Strand Break Distribution in 3D Genome and Ionizing Radiation-Induced Cell Death.","authors":"Ankang Hu, Wanyi Zhou, Xiyu Luo, Rui Qiu, Junli Li","doi":"10.1667/RADE-24-00277.1","DOIUrl":"10.1667/RADE-24-00277.1","url":null,"abstract":"<p><p>The target theory is the most classical hypothesis explaining radiation-induced cell death, yet the physical or biological nature of the \"target\" remains ambiguous. This study hypothesizes that the distribution of DNA double-strand breaks (DSBs) within the 3D genome is a pivotal factor affecting the probability of radiation-induced cell death. We propose that clustered DSBs in DNA segments with high-interaction frequencies are more susceptible to leading to cell death than isolated DSBs. Topologically associating domains (TAD) can be regarded as the reference unit for evaluating the impact of DSB clustering in the 3D genome. To quantify this correlation between the DSB distribution in 3D genome and radiation-induced effect, we developed a simplified model considering the DSB distribution across TADs. Utilizing track-structure Monte Carlo codes to simulate the electron and carbon ion irradiation, and we calculated the incidence of each DSB case across a variety of radiation doses and linear energy transfers (LETs). Our simulation results indicate that DSBs in TADs with frequent interactions (case 3) are significantly more likely to induce cell death than clustered DSBs within a single TAD (case 2). Moreover, case 2 is significantly more likely to induce cell death than isolated DSBs (case 1). The curves of the incidence of cases 2 and 3 compared with LETs have a similar shape to the radiation quality factor (Q) used in radiation protection. This indicates that these two cases are also associated with the stochastic effects induced by high-LET radiation. Our study underscores the crucial significance of the 3D genome structure in the fundamental mechanisms of radiobiological effects. The hypothesis in our research offers novel perspectives on the mechanisms that regulate radiobiological effects. Moreover, it serves as a valuable reference for the establishment of mechanistic models that can predict cell survival under different doses and LETs.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"421-432"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidants Ameliorates Ionizing Radiation-Induced Microcephaly in Cerebral Organoid Derived from Human-induced Pluripotent Stem Cells.","authors":"Mikio Shimada, Yoshihisa Matsumoto","doi":"10.1667/RADE-25-00017.1","DOIUrl":"10.1667/RADE-25-00017.1","url":null,"abstract":"<p><p>Ionizing radiation exposure induces DNA damage and chromosome aberrations through both direct and indirect effect. The indirect effects are primarily mediated by the generation of hydroxyl radicals, a process attributed to radiation. Dimethyl sulfoxide (DMSO) and ascorbic acid (AA) are known as radical scavengers and have radioprotective effects. Radiation therapy is widely employed in the treatment of malignant tumors such as glioblastoma; however, its side effects, including cognitive impairments resulting from damage to healthy neurons, pose significant challenges. To ameliorate these effects, radioprotective reagents have been sought. In this study, we used cerebral organoids derived from human-induced pluripotent stem cells to address the radioprotective effect of radical scavengers, DMSO and AA in brain exposure. Although exposure to radiation for 20-day-old cerebral organoids results in DNA double-strand breaks and apoptosis leading to microcephaly phenotype, treatment with DMSO or AA not only before but also after radiation alleviated DNA damage, cell death, and the microcephaly phenotype. Our results suggest that DMSO and AA are candidates for the radioprotective reagents for brain tumor therapy.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"410-420"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The EGFR Pathway as a Potential Therapeutic Target for Modulation of Radiation-induced Liver Injury.","authors":"Satoshi Omiya, Juan Dalo, Yuki Ueda, Uma Shankavaram, Elisa Baldelli, Valerie Calvert, Michelle Bylicky, Emanuel F Petricoin, Molykutty J Aryankalayil","doi":"10.1667/RADE-24-00203.1","DOIUrl":"10.1667/RADE-24-00203.1","url":null,"abstract":"<p><p>Radiation exposure can result in various complications influenced by factors such as dose, the amount of tissue exposed, and the type of tissue exposed. Radiation-induced liver injury (RILI) is a concern in cancer patients receiving thoracic and upper abdominal radiation, but it can also be a risk for civilians exposed to radiation in a nuclear event. RILI can lead to organ dysfunction or death; a deeper understanding of how radiation causes damage to normal tissue could pave the way for new treatments. In our study, we focused on the effects of radiation on the two main liver cell types: liver sinusoidal endothelial cells (LSECs) and hepatocytes. We exposed these cells to different doses of radiation (2, 4 or 8 Gy) as well as a sham irradiation (0 Gy) control. Proteins were extracted at 30 min, 6 h and 24 h postirradiation and analyzed using reverse phase protein array (RPPA). We observed changes to the Hepatic fibrosis signaling pathway, IL-8 signaling, and S100 family signaling pathways across multiple doses and time points in LSECs. In hepatocytes, radiation affected different pathways; we see changes in the Th1 and Th2 signaling pathways and the IL-10 signaling pathway. These pathways are critical in mediating the immune response, with Th1 being associated with pro-inflammatory responses and Th2 with anti-inflammatory responses. Hub proteins from protein-protein interaction (PPI) networks across all time points for both LSECs and hepatocytes highlighted EGFR as a top-ranked protein, indicating the potential role in mitigating radiation damage in liver cells. Herein, we showed alterations in protein expression after RILI using RPPA at early time points (hours to days) to determine potentially targetable molecular pathways. We further highlighted potential therapeutic protein markers, including EGFR, as an example of the potential utility of RPPA in target discovery.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"293-303"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Evaluation of Novel 18F-labeled Oxadiazole-based Positron Emission Tomography Tracers for β-Amyloid.","authors":"Zhongyuan Qi, Wantong Guo, Mengchao Cui, Jie Lu","doi":"10.1667/RADE-25-00035.1","DOIUrl":"10.1667/RADE-25-00035.1","url":null,"abstract":"<p><p>This research details the synthesis, structure-activity evaluation, and analysis of novel oxadiazole-based compounds for visualizing β-amyloid (Aβ) in Alzheimer's disease (AD). The derivatives exhibited binding affinities to Aβ aggregates in vitro. The [18F]-labeled compounds, [18F]4-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-N, N-dimethylaniline (compound [18F] 3) and [18F] 4-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-N-methylaniline (compound [18F]4), effectively labeled Aβ plaques in brain sections from Alzheimer's disease patients and APP/PS1 mice. In dynamic positron emission tomography (PET) studies on healthy mice, these compounds demonstrated favorable brain uptake followed by clearance. Additional structural alterations to compounds [18F] 3 and [18F] 4 may lead to the development of more efficient PET tracers for precise visualization of Aβ plaques.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"357-365"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symbolic Regression: A Versatile Approach for Constructing Phenomenological Models of Radiobiological Effects.","authors":"Ankang Hu, Wanyi Zhou, Rui Qiu, Junli Li","doi":"10.1667/RADE-24-00213.1","DOIUrl":"10.1667/RADE-24-00213.1","url":null,"abstract":"<p><p>The development of quantitative models that correlate physical, chemical, and biological parameters with radiobiological effects is imperative in the domains of radiotherapy and radiation protection. Due to the challenges associated with quantifying underlying mechanisms, phenomenological models are frequently established in preference to mechanistic models. However, the lack of a universal methodology for constructing phenomenological models presents a significant challenge in the field. We employ symbolic regression as a method for constructing phenomenological models. We attempt to develop models for the survival fraction, microdosimetric parameters, the radiation oxygen effect, and the FLASH effect. Additionally, we compare the results obtained from our symbolic regression approach with existing formulas in the scientific literature to assess the efficacy and validity of our method. Symbolic regression yields multiple simple formulas for each modeling task undertaken. These formulas demonstrate a comparable ability to predict radiobiological effects as the formulas presented in previous scientific publications. Our findings propose that symbolic regression is an automated and flexible strategy for constructing phenomenological models of radiobiological effects. Additionally, they underscore that the interpretability of a model is as crucial as its goodness of fit, as symbolic regression can identify various distinct formulas that adequately fit the provided data points.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"333-340"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Radiation-induced Brain Injury in Mice Based on Bioinformatics Analysis.","authors":"Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang","doi":"10.1667/RADE-24-00204.1","DOIUrl":"10.1667/RADE-24-00204.1","url":null,"abstract":"<p><p>Radiation therapy is a crucial adjunct treatment for head and neck tumors, as well as primary or metastatic brain tumors. Radiation-induced brain injury is one of the most severe complications, postirradiation, in patients with head and neck tumors, and significantly impacts their quality of life. Currently, there are no effective treatments for radiation-induced brain injury, making the study of radiation-induced molecular mechanisms and the identification of early damage biomarkers critical for the early diagnosis and treatment of such injuries. In this study, twelve male C57 mice aged 6-8 weeks were randomly divided into a control group, a 15 Gy irradiation group, and a 30 Gy irradiation group. Mice were exposed to 6 MV X rays. The control group underwent the same anesthesia procedure as the irradiated groups but did not receive radiation. General health and weight changes were monitored and recorded. Four months postirradiation, mice were subjected to intracranial magnetic resonance imaging [T2-weighted imaging (T2WI)], open field test (OFT), novel object recognition (NOR), followed by a collection of brain tissues for immunofluorescence, SA-β-gal staining, and transcriptomic and metabolomic analyses. Compared to the control group, the 15 Gy and 30 Gy irradiated mice showed reduced activity and weight loss. The irradiated mice exhibited impaired recognition memory in the NOR test and decreased body weight, but radiation had no significant effect on weight or performance in the OFT. Electron microscopy reveals significant demyelination of mouse cortex after irradiation, and MRI T2-weighted imaging demonstrated varying degrees of brain atrophy and ventricular enlargement in irradiated mice compared to the control group. Immunofluorescence staining showed a significant increase in astrocytes and microglia activated after irradiation. SA-β-gal staining revealed significant increases in the numbers of β-gal+ cells in irradiated mice compared to those in untreated control mice. Bioinformatics analysis identified enriched pathways primarily related to lipid metabolism and neuroinflammatory responses; associated metabolites and genes were variously upregulated or downregulated. The findings suggest that radiation-induced brain injury involves complex biological processes, with lipid metabolism disorders and neuroinflammation being the predominant pathological changes observed. Further studies on these metabolic pathways and genes could enhance our understanding of the pathogenic mechanisms underlying radiation-induced brain injury and identify potential therapeutic targets.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"321-332"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lethality Assessments for Acutely Irradiated Cynomolgus Macaques Under Subject-based Care.","authors":"Issa Melendez-Miranda, Oluseyi O Fatanmi, Stephen Y Wise, Sarah A Petrus, Alana D Carpenter, Cara Olsen, Artur A Serebrenik, Luis A Lugo-Roman, Thomas M Seed, Michael D Kaytor, Vijay K Singh","doi":"10.1667/RADE-24-00223.1","DOIUrl":"10.1667/RADE-24-00223.1","url":null,"abstract":"<p><p>Well-characterized animal models of acute radiation syndrome are needed for the development of radiation medical countermeasures to mitigate injury due to acute exposure to high doses of total- or partial-body radiation. Such animal models must reveal a radiation dose- and time-dependent relationship, pathogenesis of injury, and clinical presentation similar to humans. The focus of this study was to investigate clinical responses, principally lethality patterns, of cynomolgus macaques acutely exposed to relatively high doses of total-body radiation. Such investigations are currently relevant due to the limited availability of rhesus macaques, the dominant and preferred macaque subspecies, due to limited supply and their use in other high-priority areas. In this study employing cynomolgus macaques, a preliminary dose-response relationship was determined using three different radiation doses (4.7, 5.8 and 6.5 Gy, n = 24, n = 8/radiation dose) at a dose rate of 0.6 Gy/min. Animals were provided subject-based supportive care excluding blood products and were monitored for 60 days postirradiation for survival, which was the primary endpoint and the secondary endpoint was hematopoietic recovery. The lethality curve suggested LD30/60, LD50/60, and LD70/60 values as 4.8, 5.3, and 5.8 Gy, respectively. The initial results of this study are deemed critical for future efficacy assessments of newly developed medical countermeasures for acute radiation injuries by making use of an alternative subspecies of macaques, namely cynomolgus macaques (Macaca fascicularis).</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"304-320"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}