Le Ma, Zhihe Hu, Yan Chen, Zhuo Cheng, Chunmeng Shi
{"title":"Characterization of Two Stable Biodosimeters for Absorbed Ionizing Radiation Dose Estimation in Multiple Combined Injury Models.","authors":"Le Ma, Zhihe Hu, Yan Chen, Zhuo Cheng, Chunmeng Shi","doi":"10.1667/RADE-24-00261.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00261.1","url":null,"abstract":"<p><p>Radiation damage and deposition caused by radiological or nuclear public health incidents (e.g., accidents or attacks) may lead to acute radiation syndrome and other complications. Accurate and effective radiation dose assessment is necessary for triaging irradiated patients and determining treatment plans. However, there is no systematic evaluation of whether radiation biodosimetry is affected by comorbidities. The weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEG) co-analysis of the RNA-sequencing data in human peripheral blood after irradiation from the Gene Expression Omnibus (GEO) database identified seven radiation-specific genes, including five upregulated genes and two downregulated genes. Five radiation-specific genes (CCNG1, CDKN1A, GADD45A, GZMB, PHLDA3) showed a strong linear correlation with the total-body X-ray radiation model. The above five genes were used to validate further several radiation combined injury models, including infection, trauma, and burns, while considering different sexes and ages in animal studies on the radiation response from 0 to 10 Gy. The receiving operator characteristic (ROC) curve analysis revealed that the CCNG1 and CDKN1A genes performed the best in radiation dose-response across both mice and humans. Moreover, the CCNG1 protein could accurately predict the absorbed doses for up to 28 days after exposure (>95%). Our findings suggested that the CCNG1 and CDKN1A mRNA performed optimally in radiation dose response, independent of trauma, burns, age, and sex. Additionally, the CCNG1 protein revealed a strong linear correlation between radiation dose and time postirradiation. Our study demonstrated the potential feasibility of using CCNG1 and CDKN1A as injury biomarkers in radiation accident management.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045952","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}
Alana D Carpenter, Issa Melendez-Miranda, Yaoxiang Li, Jeyalakshmi Kandhavelu, Oluseyi O Fatanmi, Stephen Y Wise, Amrita K Cheema, Vijay K Singh
{"title":"Proteomic Changes in Preterminal Serum Samples of Rhesus Macaques Exposed to Two Different Doses of Acute Lethal Total-body Gamma Radiation.","authors":"Alana D Carpenter, Issa Melendez-Miranda, Yaoxiang Li, Jeyalakshmi Kandhavelu, Oluseyi O Fatanmi, Stephen Y Wise, Amrita K Cheema, Vijay K Singh","doi":"10.1667/RADE-25-00029.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00029.1","url":null,"abstract":"<p><p>Ionizing radiation exposure induces cellular and molecular damage, leading to a chain of events that results in tissue and organ injury. Proteomics studies help identify, validate, and quantify alterations in protein abundance downstream of radiation-induced genomic changes. The current study strives to characterize and validate the proteomic changes in the preterminal stage (moribund animals) serum samples collected from rhesus macaques lethally and acutely irradiated with two different doses of cobalt-60 gamma-radiation. Peripheral blood samples were collected prior to exposure, after exposure, and at the preterminal stage from nonhuman primates (NHPs) that did not survive after 7.2 or 7.6 Gy total-body irradiation (LD60-80/60). Using mass spectrometry-based proteomics, we analyzed samples collected at various time points after irradiation. Our findings revealed that radiation induced significant time-dependent proteomic alterations compared to pre-exposure samples. More pronounced dysregulation in pathways related to immune response and hemostasis, specifically platelet function, was present in preterminal samples, suggesting that alterations in these pathways may indicate the preterminal phenotype. These results offer important insights for the identification and validation of biomarkers for radiation-induced lethality that would be of great importance for triage during a radiological/nuclear mass casualty event.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026267","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}
Yueshan Feng, Jiaxing Yu, Lixin Xu, Haohan Lu, Hongyun Zhang, Zhengsong Li, Roberta Kungulli, Tao Hong, Mo Zhang, Jie Lu, Hongqi Zhang, Sishi Xiang
{"title":"Development of an Experimental Platform for Gamma Knife Radiosurgery in Mouse Brains.","authors":"Yueshan Feng, Jiaxing Yu, Lixin Xu, Haohan Lu, Hongyun Zhang, Zhengsong Li, Roberta Kungulli, Tao Hong, Mo Zhang, Jie Lu, Hongqi Zhang, Sishi Xiang","doi":"10.1667/RADE-24-00198.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00198.1","url":null,"abstract":"<p><p>The limited availability of post-Gamma Knife radiosurgery (GKRS) samples and the unsuitability of clinical GKRS devices for small animals highlight the need to develop devices that enable the application of a clinical GKRS device in mouse models. This study introduces a novel platform specifically designed for utilizing the Leksell Gamma Knife in mouse studies. The 3D-printed device comprises a positioning platform and a head fixation device. Six-week-old C57BL/6N mice underwent irradiation targeting the left caudate putamen (CPu) or left anterior frontobase areas. Clinical Gamma Knife prescription doses (central radiation doses of 80 Gy, 60 Gy, 50 Gy, 40 Gy, 20 Gy, and 10 Gy) were administered as single exposures. Dose conversion experiments confirmed that the actual radiation dose delivered to mice was consistently 1.5-fold higher than the planned clinical dose. MRI and H&E staining revealed clear radiation necrosis (RN) in the targeted areas when the planned clinical dose of 80 Gy was applied to the CPu and anterior frontobase, confirming the device's accuracy. γ-H2AX staining showed significant DNA double-strand breaks in the targeted region, particularly after a planned clinical dose of 40 Gy and higher. H&E staining also indicated parenchymal hemorrhage, tissue loss, and edema in the targeted areas among groups exposed to the planned clinical central doses of 80 Gy, 60 Gy, and 50 Gy. Immunofluorescence staining of CD68, IBA1, and NeuN showed significant neuroinflammation in the targeted areas of the high-dose groups (planned clinical doses of 80 Gy, 60 Gy, 50 Gy, or 40 Gy), characterized by increased microglia activation, macrophage infiltration, and neuronal death. This study developed a novel mouse platform for the Leksell Gamma Knife, enabling precise GKRS in mouse brains. For adult C57BL/6N mice, a planned clinical central dose of 40 Gy may be considered a suitable threshold for radiation-induced brain injury.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051017","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}
Jeffrey C Buchsbaum, Henry F VanBrocklin, Reinier Hernandez, Ellen M O'Brien, Heather M Hennkens, Dmitri G Medvedev, Roger W Howell, Freddy E Escorcia, Yuni K Dewaraja, Abhinav K Jha, Anuj J Kapadia, Greeshma Agasthya, Arman Rahmim, Babak Saboury, Kristian Myhre, Sandra Davern
{"title":"Computational Modeling to Advance Novel Medical Isotopes for Radiotheranostics: A DOE-NIH Joint Workshop Executive Summary.","authors":"Jeffrey C Buchsbaum, Henry F VanBrocklin, Reinier Hernandez, Ellen M O'Brien, Heather M Hennkens, Dmitri G Medvedev, Roger W Howell, Freddy E Escorcia, Yuni K Dewaraja, Abhinav K Jha, Anuj J Kapadia, Greeshma Agasthya, Arman Rahmim, Babak Saboury, Kristian Myhre, Sandra Davern","doi":"10.1667/RADE-25-00MR1.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00MR1.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014554","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}
Satoshi Omiya, Juan Dalo, Yuki Ueda, Uma Shankavaram, Elisa Baldelli, Valerie Calvert, Michelle Bylicky, Emanuel F Petricoin, Molykutty J Aryankalayil
{"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":"","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":"","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":"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}
Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang
{"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}
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
{"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}
Juliann G Kiang, Georgetta Cannon, Min Zhai, Matthew G Olson, Akeylah K Woods, Katherine S Cleveland, Hengying Ellery, Feng Xu, Mang Xiao
{"title":"A Combined Therapy of Pegylated G-CSF with Ciprofloxacin Mitigates Damage Induced by Lethal Ionizing Radiation to the Bone Marrow, Spleen, and Ileum by Increasing AKT Activation but Decreasing IL-18, C3, and miR-34a.","authors":"Juliann G Kiang, Georgetta Cannon, Min Zhai, Matthew G Olson, Akeylah K Woods, Katherine S Cleveland, Hengying Ellery, Feng Xu, Mang Xiao","doi":"10.1667/RADE-24-00266.1","DOIUrl":"10.1667/RADE-24-00266.1","url":null,"abstract":"<p><p>Ciprofloxacin (CIP) was found to enhance pegylated G-CSF therapy (PEG, Neulasta®)-induced survival from 30% to 85% after ionizing radiation exposure. This combined therapy significantly mitigated radiation-induced brain hemorrhage through its capability to improve platelet recovery. This study tested whether this combined treatment also mitigated gastrointestinal damage from radiation. B6D2F1 female mice were exposed to 60Co γ radiation. CIP was fed daily to mice for up to 14 days. PEG was injected on day 1, and then weekly up to day 14. For the early time point study, blood, femurs, spleen, and ileum were collected on days 2, 4, 9, and 15 postirradiation. Bone marrow cells were counted; spleen weights and splenocyte counts were measured; and ileum histopathology was examined and analyzed. AKT, ERK, JNK, p38, claudin 2, NF-kB, Bax, Bcl-2, and gasdermin D were measured in ileum lysates using Western blotting while miR-34a was measured by reverse transcription followed by real-time-PCR, and citrulline was measured by colorimetric assay. In serum, interleukin-18 (IL-18) was measured by Luminex assay and complement protein 3 (C3) was detected by ELISA. The bacterial DNA load in livers was measured by real-time PCR. Radiation depleted bone marrow cells in femurs beginning day 2 through day 15 postirradiation, which was mitigated by PEG or CIP+PEG on day 9 through day 15 and by CIP on day 15, respectively. Radiation exposure led to decreased spleen weight on day 2 through day 15, while PEG or CIP+PEG significantly mitigated the reduction on day 9 through day 15. Radiation exposure reduced splenocyte counts on day 2 through day 15 postirradiation, but that was mitigated by PEG or CIP+PEG on day 15. Ileum histology showed that radiation decreased villus height on day 2 through day 15; CIP mitigated the reduction on day 15, whereas PEG+CIP mitigated it on day 2 through 15. Villus widths were increased on day 2 through day 15, while PEG+CIP effectively decreased them on day 4 through day 15. Crypt depth was reduced by radiation on day 2, but returned to the baseline on day 4 through 15. CIP or CIP+PEG transiently increased the depth only on day 4. Crypt counts were reduced by radiation on days 2 and 4, but returned to the baseline on days 9 and 15, regardless of individual drugs or combinations. Citrulline data confirmed the villus height recovery. Radiation significantly increased pro-inflammatory cytokine IL-18 on days 4 and 9, which was mitigated by PEG alone or PEG+CIP, but not by CIP alone. Radiation increased C3 on day 9 in ileum and serum. The serum C3 was positively associated with the serum IL-18 levels and negatively correlated with the crypt depth. Radiation-induced decreases in claudin 2 (a tight junction marker) in ileum and increases in bacterial DNA in livers were mitigated by PEG+CIP. Radiation did not reduce NF-kB and its activation but reduced Bcl-2 expression, which was not significantly recovered by any individual drug or combinat","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"341-356"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781102","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}