Xinrui Rao, Hongyuan Liu, Yuewen Zhang, Yaqiong Xie, Geng Wang, Sheng Zhang, Gang Wu, Ye Wang, Rui Zhou
{"title":"The relationship of body mass index to setup errors, dosimetric parameters and incidence of radiation pneumonitis in non-small cell lung cancer patients undergoing intensity-modulated radiation therapy: a single-center observational study.","authors":"Xinrui Rao, Hongyuan Liu, Yuewen Zhang, Yaqiong Xie, Geng Wang, Sheng Zhang, Gang Wu, Ye Wang, Rui Zhou","doi":"10.1080/09553002.2023.2261549","DOIUrl":"10.1080/09553002.2023.2261549","url":null,"abstract":"<p><strong>Background: </strong>The relationship among body mass index (BMI), setup error and radiation pneumonitis is not clearly illustrated.</p><p><strong>Objective: </strong>The present study aimed to investigate the role of BMI in non-small cell lung cancer (NSCLC) patients' radiation treatment, focusing on its relationship with setup error of patient positioning, the dosimetric parameters of intensity-modulated radiation therapy (IMRT) and the incidence of radiation pneumonitis.</p><p><strong>Methods: </strong>This prospective observational study included 523 cases of NSCLC patients during 2020-2022. Patients were divided into different groups by different BMI. The setup error was obtained by cone beam CT (CBCT) at three positions, lateral (LAT), longitudinal (LNG) and vertical (VRT). IMRT dosimetric parameters of <i>V</i><sub>5</sub>, <i>V</i><sub>20</sub>, and mean dose were collected.</p><p><strong>Results: </strong>Patients with BMI ≥28 kg/m<sup>2</sup> showed significantly higher absolute values of LAT, LNG and VRT, higher <i>V</i><sub>5</sub>, <i>V</i><sub>20</sub>, mean dose, as well as higher total incidence of radiation pneumonitis and grade III radiation pneumonitis compared with patients with BMI <24 kg/m<sup>2</sup> or 24-28 kg/m<sup>2</sup>. Spearman's analysis demonstrated that the absolute values of LAT, LNG and VRT were positively correlated with BMI, and positive correlation existed among BMI, dosimetric parameters and setup errors. ROC curves showed that LAT in setup errors and <i>V</i><sub>5</sub> in dosimetric parameters had the best diagnostic value for prediction of radiation pneumonitis. Only BMI, LAT, <i>V</i><sub>5</sub> and <i>V</i><sub>20</sub> were the independent risk factors for radiation pneumonitis.</p><p><strong>Conclusions: </strong>Setup error caused by higher BMI might be associated with the dosimetric parameters, as well as the incidence of radiation pneumonitis in NSCLC patients.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"248-255"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Co<sup>60</sup> gamma irradiation reduces rooting ability in M<sub>1</sub>V<sub>1</sub> <i>Salvia uliginosa</i> while inducing leaf variegation.","authors":"Rebekah C I Maynard, John M Ruter","doi":"10.1080/09553002.2024.2304852","DOIUrl":"10.1080/09553002.2024.2304852","url":null,"abstract":"<p><strong>Purpose: </strong><i>Salvia uliginosa</i> is a desirable ornamental shrub for the landscape with blue flowers and the ability to attract pollinators, but limited variation is commercially available in this species. Mutation breeding is a valuable tool to induce variation in ornamental species. However, many deleterious effects are associated with mutation breeding, including reduced rooting ability of vegetative cuttings.</p><p><strong>Materials and methods: </strong>Cuttings of <i>S. uliginosa</i> were randomly assigned into groups of 10 and exposed to 0, 10, 20, 30, 40, or 50 Gy of gamma rays from a cobalt-60 source to determine an appropriate treatment rate. A follow-up experiment treated 25 <i>S. uliginosa</i> cuttings at 35 Gy to induce favorable mutations.</p><p><strong>Results and conclusions: </strong>Root quality, survival, and plant height were reduced at higher levels of gamma radiation in the M<sub>1</sub>V<sub>1</sub>. However, rooting ability was not impacted in M<sub>1</sub>V<sub>2</sub> selections. Additionally, one mutant was isolated from the 35 Gy treatment with variegated leaves for a mutation rate of 4%. Our research determined a treatment rate that induced a dominant mutation in <i>S. uliginosa</i> while minimizing the deleterious influence of gamma radiation.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"663-668"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Review of the evidence of radioprotective potential of creatine and arginine as dietary supplements.","authors":"Lyudmila Nersesova, Mariam Petrosyan, Gohar Tsakanova","doi":"10.1080/09553002.2024.2345098","DOIUrl":"10.1080/09553002.2024.2345098","url":null,"abstract":"<p><strong>Purpose: </strong>Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes' workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups.</p><p><strong>Conclusions: </strong>Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD<sub>70/30</sub> dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr-Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"849-864"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Defining the role of Tip60 in the DNA damage response of glioma cell lines.","authors":"K Bannik, A Sak, M Groneberg, M Stuschke","doi":"10.1080/09553002.2024.2409668","DOIUrl":"10.1080/09553002.2024.2409668","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastomas are resistant to conventional therapies, including radiotherapy. Our previous study proved that epigenetic regulation influences the radiation response of glioma cells. This study evaluated the role of the acetyltransferase Tip60 on the radiation response.</p><p><strong>Material and methods: </strong>Tip60 expression was down-regulated by transfecting specific siRNA's in A7 and MO59K cells with high and low expression of Tip60, respectively, and its effect on survival was assessed. DNA repair was analyzed by foci scoring (γH2AX, Rad51, 53BP1, pATM). The interaction of Tip60 with ATM and DNA-PK was investigated using the specific inhibitors KU55933 and NU7441, respectively.</p><p><strong>Results: </strong>Knockdown of Tip60 significantly (<i>p</i> < .001) reduced survival in both cell lines, but the effect was more pronounced in A7 cells. ATMi and DNA-PKi significantly reduced the surviving fraction following irradiation. However, no further effect of siTip60 on the radiosensitivity of ATMi treated A7 cells was observed. In contrast, DNA-PKi effectively enhanced the sensitizing effect of siTip60. Mechanistically, siTip60 reduced the number of initial Rad51 and ATM foci formation after irradiation and prevented their dissolution at 24 h. siTip60 had no impact on the formation of 53BP1 and γH2AX foci and did not further affect these end-points if combined with ATMi or DNA-PKi.</p><p><strong>Conclusions: </strong>Downregulation of Tip60 enhances the radiation sensitivity of both glioma cells and markedly elevates the radiation sensitivity when combined with DNA-PKi. Therefore, treatment with DNA-PK inhibitors represents a promising approach to augment the radiation sensitivity of glioma cell lines with deficient Tip60 activity in a synergistic manner.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1622-1632"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma.","authors":"Tong Hu, Gai-Ting Liu, Dan-Dan Wang, Yan-Tao Xiao, Wen-Feng Gou, Dai-Ying Zuo, Wen-Bin Hou, Yi-Liang Li","doi":"10.1080/09553002.2024.2381490","DOIUrl":"10.1080/09553002.2024.2381490","url":null,"abstract":"<p><strong>Purpose: </strong>Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo.</p><p><strong>Methods: </strong>MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo.</p><p><strong>Results: </strong>In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect.</p><p><strong>Conclusion: </strong>SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1453-1461"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radia Tamarat, Merriline M Satyamitra, Marc Benderitter, Andrea L DiCarlo
{"title":"Radiation-induced gastrointestinal and cutaneous injuries: understanding models, pathologies, assessments, and clinically accepted practices.","authors":"Radia Tamarat, Merriline M Satyamitra, Marc Benderitter, Andrea L DiCarlo","doi":"10.1080/09553002.2024.2356544","DOIUrl":"10.1080/09553002.2024.2356544","url":null,"abstract":"<p><strong>Purpose: </strong>A U. S. and European joint effort fostering the development of medical countermeasures (MCMs) operable in case of radiological or nuclear emergencies.</p><p><strong>Methods: </strong>Based on the joint engagement between the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the French Institut de Radioprotection et de Sûreté Nucléaire (IRSN), a Statement of Intent to Collaborate was signed in 2014 and a series of working group meeting were established. In December 2022, the NIAID and IRSN hosted a five-day, U.S./European meeting titled 'Radiation-Induced Cutaneous and Gastrointestinal Injuries: Advances in Understanding Pathologies, Assessment, and Clinically Accepted Practices' in Paris, France. The goals of the meeting were to bring together U.S. and European investigators to explore new research avenues for the medical management of skin and gastrointestinal injuries, including specific diagnostics for each organ system, animal models, and promising medical countermeasures (MCMs) to mitigate radiation damage. There was also an emphasis on exploring additional areas of medicine and response to understand best practices from other emergency scenarios, which could be leveraged to improve radiation preparedness, and the importance of accurate dosimetry in preclinical work.</p><p><strong>Results: </strong>Subsequent to the workshop, seven collaborative projects, funded by both organizations, were established on topics ranging from MCMs and predictive biomarkers, and using physical methods to assess cutaneous radiation injuries, to mechanistic studies to understand radiation-induced damage in multiple organ systems. The importance of accurate dosimetry in preclinical works was highlighted and two recently published U.S./European commentaries that focus on the need for dosimetry standardization in the reported literature had their origins in this meeting. This commentary summarizes the workshop and open discussions among academic investigators, industry researchers, and U.S. and IRSN program representatives.</p><p><strong>Conclusions: </strong>Given the substantive progress made due to these interactions, both groups plan to expand out these meetings by incorporating high-level investigators from across the globe, while endeavoring to maintain the informal setting that was conducive to in-depth scientific discussion and enhanced the state of the science in radiation research.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"969-981"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of ionizing radiation exposure in offspring and next generations.","authors":"Christian Streffer, M Prakash Hande","doi":"10.1080/09553002.2024.2384834","DOIUrl":"10.1080/09553002.2024.2384834","url":null,"abstract":"","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1237-1239"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victoria L Korogodina, Valeri B Arakelyan, Ashot A Chilingarian, Ruben Danielyan, Marina V Gustova, Svetlana P Kaplina, Garnik E Khachatryan, Arsen F Manucharyan, Gayane G Melik-Andreasyan, Balabek Sargsyan
{"title":"Adaptation to mountain γ-background: bacteria speciation.","authors":"Victoria L Korogodina, Valeri B Arakelyan, Ashot A Chilingarian, Ruben Danielyan, Marina V Gustova, Svetlana P Kaplina, Garnik E Khachatryan, Arsen F Manucharyan, Gayane G Melik-Andreasyan, Balabek Sargsyan","doi":"10.1080/09553002.2024.2396378","DOIUrl":"10.1080/09553002.2024.2396378","url":null,"abstract":"<p><strong>Purpose: </strong>To study the adaptation of bacteria to the natural γ-background of mountains and anthropogenic emissions from nuclear power plants; to establish the main factors of variability and speciation of bacteria.</p><p><strong>Method: </strong>Analysis of materials on the radiation background and its impact on living organisms in the landscape of Armenia, calculation of the absorbed dose by microbes due to rock radiation.</p><p><strong>Results: </strong>The review shows the death, reproduction, radioresistance and speciation of bacteria in changing conditions of low variable natural and anthropogenic γ-background.</p><p><strong>Conclusion: </strong>We assume that γ-rays from rocks activate cellular epigenetic mechanisms that regulate genome expression, signaling and, ultimately, variability of bacteria. Some of them have already been studied, others require research.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1517-1526"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ingunn Hanson, Inga Solgård Juvkam, Olga Zlygosteva, Tine Merete Søland, Hilde Kanli Galtung, Eirik Malinen, Nina Frederike Jeppesen Edin
{"title":"TGF-β3 increases the severity of radiation-induced oral mucositis and salivary gland fibrosis in a mouse model.","authors":"Ingunn Hanson, Inga Solgård Juvkam, Olga Zlygosteva, Tine Merete Søland, Hilde Kanli Galtung, Eirik Malinen, Nina Frederike Jeppesen Edin","doi":"10.1080/09553002.2024.2324476","DOIUrl":"10.1080/09553002.2024.2324476","url":null,"abstract":"<p><strong>Purpose: </strong>Toxicities from head and neck (H&N) radiotherapy (RT) may affect patient quality of life and can be dose-limiting. Proteins from the transforming growth factor beta (TGF-β) family are key players in the fibrotic response. While TGF-β1 is known to be pro-fibrotic, TGF-β3 has mainly been considered anti-fibrotic. Moreover, TGF-β3 has been shown to act protective against acute toxicities after radio- and chemotherapy. In the present study, we investigated the effect of TGF-β3 treatment during fractionated H&N RT in a mouse model.</p><p><strong>Materials and methods: </strong>30 C57BL/6J mice were assigned to three treatment groups. The RT + TGF-β3 group received local fractionated H&N RT with 66 Gy over five days, combined with TGF-β3-injections at 24-hour intervals. Animals in the RT reference group received identical RT without TGF-β3 treatment. The non-irradiated control group was sham-irradiated according to the same RT schedule. In the follow-up period, body weight and symptoms of oral mucositis and lip dermatitis were monitored. Saliva was sampled at five time points. The experiment was terminated 105 d after the first RT fraction. Submandibular and sublingual glands were preserved, sectioned, and stained with Masson's trichrome to visualize collagen.</p><p><strong>Results: </strong>A subset of mice in the RT + TGF-β3 group displayed increased severity of oral mucositis and increased weight loss, resulting in a significant increase in mortality. Collagen content was significantly increased in the submandibular and sublingual glands for the surviving RT + TGF-β3 mice, compared with non-irradiated controls. In the RT reference group, collagen content was significantly increased in the submandibular gland only. Both RT groups displayed lower saliva production after treatment compared to controls. TGF-β3 treatment did not impact saliva production.</p><p><strong>Conclusions: </strong>When repeatedly administered during fractionated RT at the current dose, TGF-β3 treatment increased acute H&N radiation toxicities and increased mortality. Furthermore, TGF-β3 treatment may increase the severity of radiation-induced salivary gland fibrosis.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"767-776"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Na Li, Kejun Li, Wenyue Zhao, Yan Wang, Chang Xu, Qin Wang, Lifeng Pan, Qiang Li, Kaihua Ji, Ningning He, Yang Liu, Jinhan Wang, Manman Zhang, Mengmeng Yang, Liqing Du, Qiang Liu
{"title":"Small extracellular vesicles from irradiated lung epithelial cells promote the activation of fibroblasts in pulmonary fibrosis.","authors":"Na Li, Kejun Li, Wenyue Zhao, Yan Wang, Chang Xu, Qin Wang, Lifeng Pan, Qiang Li, Kaihua Ji, Ningning He, Yang Liu, Jinhan Wang, Manman Zhang, Mengmeng Yang, Liqing Du, Qiang Liu","doi":"10.1080/09553002.2023.2263550","DOIUrl":"10.1080/09553002.2023.2263550","url":null,"abstract":"<p><strong>Background: </strong>Alveolar epithelial injury and dysfunction are the risk factors for radiation-induced pulmonary fibrosis (RIPF). However, it is not clear about the relationship between RIPF and the small extracellular vesicles (sEV) secreted by irradiated alveolar epithelial cells. Based on the activation of fibroblasts, this study explored the role of sEV derived from alveolar epithelial cells in RIPF and the potential mechanisms.</p><p><strong>Methods: </strong>Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were used to characterize sEV. Western blotting was used to detect fibrosis-associated proteins. Cell counts and transwell assays were used to evaluate the proliferation and migration ability of fibroblasts. RT-PCR was used to observe the extracellular matrix (ECM) synthesized by fibroblasts, miRNA changes in the sEV were determined by second-generation sequencing.</p><p><strong>Results: </strong>TEM, NTA, and western blotting showed the extracellular vesicles with a double-layer membrane structure of approximately 100 nm in diameter. The sEV derived from irradiated A549, HBEC3-KT, and MLE12 cells upregulated FN1 and alpha-SMA proteins expression in fibroblasts and drove the fibroblast to myofibroblast transition, and the sEV from irradiated mouse bronchoalveolar lavage fluid (BALF) affirmed the same results. In addition, the sEV derived from irradiated alveolar epithelial cells significantly increased the migration ability of fibroblasts and the expression of extracellular matrix proteins such as FN1. The results of miRNA sequencing of sEV in BALF of rats with RIPF showed that the metabolic pathway may be important for miRNA to regulate the activation of fibroblasts.</p><p><strong>Conclusion: </strong>The sEV derived from radiated pulmonary epithelial cells promote the activation, migration and extracellular matrix proteins expression of lung fibroblasts; miRNA in sEV may be an important molecular that affects the activation of lung fibroblasts.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"268-280"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}