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Adaptation to mountain γ-background: bacteria speciation. 适应山地γ背景:细菌的分化。
Pub Date : 2024-01-01 Epub Date: 2024-09-25 DOI: 10.1080/09553002.2024.2396378
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

Purpose: 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.

Method: 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.

Results: The review shows the death, reproduction, radioresistance and speciation of bacteria in changing conditions of low variable natural and anthropogenic γ-background.

Conclusion: 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.

目的:研究细菌对山区自然γ背景和核电站人为排放物的适应情况;确定细菌变异和种类的主要因素:方法:分析有关亚美尼亚地貌辐射背景及其对生物影响的材料,计算岩石辐射导致的微生物吸收剂量:研究结果表明,在自然和人为γ本底变化较小的条件下,细菌的死亡、繁殖、抗辐射能力和种类发生了变化:我们认为,来自岩石的 γ 射线激活了细胞的表观遗传机制,这些机制调节着基因组的表达、信号传递,并最终影响细菌的变异。其中一些机制已经得到研究,另一些机制还需要研究。
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引用次数: 0
TGF-β3 increases the severity of radiation-induced oral mucositis and salivary gland fibrosis in a mouse model. 在小鼠模型中,TGF-β3 会增加辐射诱发的口腔黏膜炎和唾液腺纤维化的严重程度。
Pub Date : 2024-01-01 Epub Date: 2024-03-05 DOI: 10.1080/09553002.2024.2324476
Ingunn Hanson, Inga Solgård Juvkam, Olga Zlygosteva, Tine Merete Søland, Hilde Kanli Galtung, Eirik Malinen, Nina Frederike Jeppesen Edin

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

目的:头颈部(H&N)放射治疗(RT)的毒性可能会影响患者的生活质量,并可能限制剂量。转化生长因子β(TGF-β)家族的蛋白质是纤维化反应的关键因素。众所周知,TGF-β1 具有促纤维化作用,而 TGF-β3 则主要被认为具有抗纤维化作用。此外,TGF-β3 对放疗和化疗后的急性毒性也有保护作用。在本研究中,我们在小鼠模型中研究了分次 H&N RT 期间 TGF-β3 治疗的效果。RT + TGF-β3 组接受局部分次 H&N RT(66 Gy,共 5 天),同时每隔 24 小时注射一次 TGF-β3。RT参照组的动物接受了不含TGF-β3治疗的相同RT。非辐照对照组按照相同的辐照计划进行假辐照。在随访期间,对体重、口腔粘膜炎症状和唇皮炎进行监测。在五个时间点采集唾液样本。实验在第一部分 RT 105 d 后终止。保存下颌下腺和舌下腺,进行切片,并用马森三色染色以观察胶原蛋白:结果:RT + TGF-β3 组小鼠的口腔粘膜炎严重程度增加,体重减轻,死亡率显著上升。与非辐照对照组相比,存活的 RT + TGF-β3 小鼠颌下腺和舌下腺中的胶原蛋白含量明显增加。在 RT 参照组中,只有颌下腺的胶原蛋白含量明显增加。与对照组相比,两个 RT 组在治疗后的唾液分泌量都较低。TGF-β3治疗不会影响唾液分泌:结论:在当前剂量的分次放射治疗过程中重复给药时,TGF-β3 会增加急性 H&N 放射毒性并增加死亡率。此外,TGF-β3 治疗可能会增加辐射诱导的唾液腺纤维化的严重程度。
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引用次数: 0
Small extracellular vesicles from irradiated lung epithelial cells promote the activation of fibroblasts in pulmonary fibrosis. 来自受辐射的肺上皮细胞的细胞外小泡促进肺纤维化中成纤维细胞的活化。
Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/09553002.2023.2263550
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

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景:肺泡上皮损伤和功能障碍是放射性肺纤维化(RIPF)的危险因素。然而,RIPF与照射肺泡上皮细胞分泌的细胞外小泡(sEV)之间的关系尚不清楚。基于成纤维细胞的活化,本研究探讨了肺泡上皮细胞来源的sEV在RIPF中的作用及其潜在机制。方法:采用透射电子显微镜(TEM)、纳米粒子跟踪分析(NTA)和蛋白质印迹法对sEV进行表征。蛋白质印迹法用于检测纤维化相关蛋白。细胞计数和transwell测定用于评估成纤维细胞的增殖和迁移能力。RT-PCR法观察成纤维细胞合成的细胞外基质(ECM),第二代测序法测定sEV中miRNA的变化。结果:TEM、NTA和蛋白质印迹显示细胞外小泡具有约100的双层膜结构 直径为nm。来自照射的A549、HBEC3-KT和MLE12细胞的sEV上调了成纤维细胞中FN1和α-SMA蛋白的表达,并驱动成纤维细胞向肌成纤维细胞的转变,来自照射的小鼠支气管肺泡灌洗液(BALF)的sEV证实了相同的结果。此外,来源于辐照肺泡上皮细胞的sEV显著增加了成纤维细胞的迁移能力和细胞外基质蛋白如FN1的表达。RIPF大鼠BALF中sEV的miRNA测序结果表明,miRNA调节成纤维细胞活化的代谢途径可能很重要。结论:辐射肺上皮细胞产生的sEV可促进肺成纤维细胞的活化、迁移和细胞外基质蛋白的表达;sEV中的miRNA可能是影响肺成纤维细胞活化的重要分子。
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引用次数: 0
A clinician's perspective on boron neutron capture therapy: promising advances, ongoing trials, and future outlook. 临床医生对硼中子俘获疗法的看法:有望取得的进展、正在进行的试验以及未来展望。
Pub Date : 2024-01-01 Epub Date: 2024-07-10 DOI: 10.1080/09553002.2024.2373746
Shumin Shen, Shanghu Wang, Dachen Zhou, Xiuwei Wu, Mingzhu Gao, Jinjin Wu, Yucai Yang, Xiaoxi Pan, Nianfei Wang

Purpose: This comprehensive review aims to provide a unique clinical perspective on the latest advances and ongoing boron neutron capture therapy (BNCT) trials for various cancers.

Methods: We critically analyzed clinical data from BNCT trials for head and neck cancer, glioblastoma, melanoma, meningioma, breast cancer, and liver tumors. We investigated differences in tumor responses and normal tissue toxicities among trials and discussed potential contributing factors. We also identified the limitations of early BNCT trials and proposed strategies to optimize future trial design.

Results: BNCT has shown promising results in treating head and neck cancer, with high response rates and improved survival in patients with recurrent disease. In glioblastoma, BNCT combined with surgery and chemotherapy has demonstrated survival benefits compared to standard treatments. BNCT has also been successfully used for recurrent high-grade meningiomas and shows potential for melanomas, extramammary Paget's disease, and liver tumors. However, differences in tumor responses and toxicities were observed among trials, potentially attributable to variations in treatment protocols, patient characteristics, and evaluation methods.

Conclusions: BNCT is a promising targeted radiotherapy for various cancers. Further optimization and well-designed randomized controlled trials are needed to establish its efficacy and safety. Future studies should focus on standardizing treatment protocols and addressing limitations to guide clinical decision-making and research priorities.

目的:这篇综合综述旨在以独特的临床视角介绍各种癌症的最新进展和正在进行的硼中子俘获疗法(BNCT)试验:我们认真分析了头颈部癌症、胶质母细胞瘤、黑色素瘤、脑膜瘤、乳腺癌和肝脏肿瘤的硼中子俘获疗法试验的临床数据。我们调查了不同试验在肿瘤反应和正常组织毒性方面的差异,并讨论了潜在的诱因。我们还发现了早期 BNCT 试验的局限性,并提出了优化未来试验设计的策略:结果:BNCT 在治疗头颈部癌症方面取得了可喜的成果,复发患者的反应率高,生存率也有所提高。在胶质母细胞瘤中,BNCT与手术和化疗相结合,与标准疗法相比,生存率有所提高。BNCT 还成功用于治疗复发性高级别脑膜瘤,并显示出治疗黑色素瘤、乳腺外 Paget 病和肝脏肿瘤的潜力。然而,在不同试验中观察到的肿瘤反应和毒性存在差异,这可能与治疗方案、患者特征和评估方法的不同有关:结论:BNCT是一种治疗各种癌症的前景广阔的靶向放射疗法。结论:BNCT 是一种治疗各种癌症的有前途的靶向放射疗法,需要进一步优化和设计良好的随机对照试验来确定其疗效和安全性。未来的研究应侧重于规范治疗方案和解决局限性问题,以指导临床决策和研究重点。
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引用次数: 0
LBDNet interlaboratory comparison for the dicentric chromosome assay by digitized image analysis applying weighted robust statistical methods. 应用加权稳健统计方法,通过数字化图像分析,对双中心染色体检测进行 LBDNet 实验室间比较。
Pub Date : 2024-01-01 Epub Date: 2024-05-29 DOI: 10.1080/09553002.2024.2356556
Jorge Ernesto González Mesa, Diego Alem Glison, Fabio Andrés Chaves-Campos, Fernando Ortíz Morales, Luisa Valle Bourrouet, Melissa Abarca Ramírez, Valentina Verdejo, Marina Di Giorgio, Analía Radl, María Rosa Taja, Mayra Deminge, Ana Rada-Tarifa, Erika Lafuente-Alvarez, Fabiana Farias de Lima, Suy Hwang, Mariana Esposito Mendes, Tania Mandina-Cardoso, Gabriela Muñoz-Velastegui, Yolanda Citlali Guerrero-Carbajal, Carolina Arceo Maldonado, Norma Monjagata, Sara Aguilar-Coronel, Marco Espinoza-Zevallos, Aida Falcon de Vargas, Maria Vittoria Di Tomaso, Bret Holladay, Omar García Lima, Wilner Martínez-López

Purpose: This interlaboratory comparison was conducted to evaluate the performance of the Latin-American Biodosimetry Network (LBDNet) in analyzing digitized images for scoring dicentric chromosomes from in vitro irradiated blood samples. The exercise also assessed the use of weighted robust algorithms to compensate the uneven expertise among the participating laboratories.

Methods: Three sets of coded images obtained through the dicentric chromosome assay from blood samples irradiated at 1.5 Gy (sample A) and 4 Gy (sample B), as well as a non-irradiated whole blood sample (sample C), were shared among LBDNet laboratories. The images were captured using the Metafer4 platform coupled with the AutoCapt module. The laboratories were requested to perform triage scoring, conventional scoring, and dose estimation. The dose estimation was carried out using either their laboratory calibration curve or a common calibration curve. A comparative statistical analysis was conducted using a weighted robust Hampel algorithm and z score to compensate for uneven expertise in dicentric analysis and dose assessment among all laboratories.

Results: Out of twelve laboratories, one had unsatisfactory estimated doses at 0 Gy, and two had unsatisfactory estimated doses at 1.5 Gy when using their own calibration curve and triage scoring mode. However, all doses were satisfactory at 4 Gy. Six laboratories had estimated doses within 95% uncertainty limits at 0 Gy, seven at 1.5 Gy, and four at 4 Gy. While the mean dose for sample C was significantly biased using robust algorithms, applying weights to compensate for the laboratory's analysis expertise reduced the bias by half. The bias from delivered doses was only notable for sample C. Using the common calibration curve for dose estimation reduced the standard deviation (s*) estimated by robust methods for all three samples.

Conclusions: The results underscore the significance of performing interlaboratory comparison exercises that involve digitized and electronically transmitted images, even when analyzing non-irradiated samples. In situations where the participating laboratories possess different levels of proficiency, it may prove essential to employ weighted robust algorithms to achieve precise outcomes.

目的:本次实验室间比对旨在评估拉丁美洲生物测定网络(LBDNet)在分析数字化图像以对体外辐照血液样本中的双中心染色体进行评分方面的性能。这项工作还评估了加权稳健算法的使用情况,以弥补参与实验室之间专业知识的不均衡:方法:LBDNet 实验室共享三组通过双中心染色体检测获得的编码图像,这三组图像分别来自经过 1.5 Gy(样本 A)和 4 Gy(样本 B)辐照的血液样本,以及未经辐照的全血样本(样本 C)。图像使用 Metafer4 平台和 AutoCapt 模块采集。要求实验室进行分流评分、常规评分和剂量估算。剂量估算使用实验室校准曲线或通用校准曲线进行。使用加权稳健汉普尔算法和 z 评分进行了比较统计分析,以弥补所有实验室在二中心分析和剂量评估方面专业知识的不均衡:结果:在12个实验室中,一个实验室在使用自己的校准曲线和分流评分模式时,0 Gy时的估计剂量不能令人满意,两个实验室在使用自己的校准曲线和分流评分模式时,1.5 Gy时的估计剂量不能令人满意。但在 4 Gy 时,所有剂量都令人满意。6 个实验室在 0 Gy 时的估计剂量在 95% 不确定度范围内,7 个实验室在 1.5 Gy 时的估计剂量在 95% 不确定度范围内,4 个实验室在 4 Gy 时的估计剂量在 95% 不确定度范围内。虽然样本 C 的平均剂量在使用稳健算法时存在明显偏差,但应用权重来补偿实验室的分析专长可将偏差减半。使用通用校准曲线进行剂量估算降低了所有三个样本的稳健方法估算的标准偏差(s*):这些结果突出表明,即使在分析非辐照样本时,也要进行涉及数字化和电子传输图像的实验室间比对工作。在参与比对的实验室水平不一的情况下,采用加权稳健算法以获得精确结果可能是至关重要的。
{"title":"LBDNet interlaboratory comparison for the dicentric chromosome assay by digitized image analysis applying weighted robust statistical methods.","authors":"Jorge Ernesto González Mesa, Diego Alem Glison, Fabio Andrés Chaves-Campos, Fernando Ortíz Morales, Luisa Valle Bourrouet, Melissa Abarca Ramírez, Valentina Verdejo, Marina Di Giorgio, Analía Radl, María Rosa Taja, Mayra Deminge, Ana Rada-Tarifa, Erika Lafuente-Alvarez, Fabiana Farias de Lima, Suy Hwang, Mariana Esposito Mendes, Tania Mandina-Cardoso, Gabriela Muñoz-Velastegui, Yolanda Citlali Guerrero-Carbajal, Carolina Arceo Maldonado, Norma Monjagata, Sara Aguilar-Coronel, Marco Espinoza-Zevallos, Aida Falcon de Vargas, Maria Vittoria Di Tomaso, Bret Holladay, Omar García Lima, Wilner Martínez-López","doi":"10.1080/09553002.2024.2356556","DOIUrl":"10.1080/09553002.2024.2356556","url":null,"abstract":"<p><strong>Purpose: </strong>This interlaboratory comparison was conducted to evaluate the performance of the Latin-American Biodosimetry Network (LBDNet) in analyzing digitized images for scoring dicentric chromosomes from <i>in vitro</i> irradiated blood samples. The exercise also assessed the use of weighted robust algorithms to compensate the uneven expertise among the participating laboratories.</p><p><strong>Methods: </strong>Three sets of coded images obtained through the dicentric chromosome assay from blood samples irradiated at 1.5 Gy (sample A) and 4 Gy (sample B), as well as a non-irradiated whole blood sample (sample C), were shared among LBDNet laboratories. The images were captured using the Metafer4 platform coupled with the AutoCapt module. The laboratories were requested to perform triage scoring, conventional scoring, and dose estimation. The dose estimation was carried out using either their laboratory calibration curve or a common calibration curve. A comparative statistical analysis was conducted using a weighted robust Hampel algorithm and z score to compensate for uneven expertise in dicentric analysis and dose assessment among all laboratories.</p><p><strong>Results: </strong>Out of twelve laboratories, one had unsatisfactory estimated doses at 0 Gy, and two had unsatisfactory estimated doses at 1.5 Gy when using their own calibration curve and triage scoring mode. However, all doses were satisfactory at 4 Gy. Six laboratories had estimated doses within 95% uncertainty limits at 0 Gy, seven at 1.5 Gy, and four at 4 Gy. While the mean dose for sample C was significantly biased using robust algorithms, applying weights to compensate for the laboratory's analysis expertise reduced the bias by half. The bias from delivered doses was only notable for sample C. Using the common calibration curve for dose estimation reduced the standard deviation (<i>s</i>*) estimated by robust methods for all three samples.</p><p><strong>Conclusions: </strong>The results underscore the significance of performing interlaboratory comparison exercises that involve digitized and electronically transmitted images, even when analyzing non-irradiated samples. In situations where the participating laboratories possess different levels of proficiency, it may prove essential to employ weighted robust algorithms to achieve precise outcomes.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1019-1028"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141177152","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}
引用次数: 0
Absorption of 5G sub-6 GHz electromagnetic radiation from base station to male reproduction system. 从基站到男性生殖系统对 5G sub-6 GHz 电磁辐射的吸收。
Pub Date : 2024-01-01 Epub Date: 2024-05-06 DOI: 10.1080/09553002.2024.2347354
Jiajin Lin, Jing Li, Guirong Ding

Background: The impact of electromagnetic radiation from communication on the male reproductive system has emerged as a significant concern in public health. A notable distinction of the 5G sub-6 GHz band, compared to traditional 2G, 3G, and 4G frequency bands, is the inclusion of higher frequency bands. This has raised public concerns regarding the potential effects of these higher frequencies on organisms, particularly their reproductive systems. While it is imperative to investigate the biological effects and potential risks associated with these new frequency bands in laboratory settings, comparing and evaluating differences between various frequency bands remain challenging due to the absence of standardized parameters such as exposure conditions and duration. In contrast, dose assessment offers a simpler and more reliable approach.

Materials and methods: The dose assessment method was employed in this study to investigate the risks associated with sub-6 GHz electromagnetic radiation from 5G base stations on the male reproductive system. A classical human body model (Duke) was utilized, and an electromagnetic simulation environment was established based on the actual polarization direction of the exposed base stations and various body postures. This research explored the effects of field direction, posture, public population, and frequency on the specific absorption rate of the reproductive system.

Results and conclusions: While maintaining the same level of exposure, a higher frequency results in a reduced dosage on reproductive system. Further analysis reveals that, considering the public exposure threshold, the employment of higher frequency bands in 5G sub-6 GHz does not present a greater dosage on reproductive system compared to lower frequency bands. Consequently, with regard to dosage, there is no need for excessive concern among the general public regarding the impact of electromagnetic radiation emitted by 5G base stations operating below 6 GHz on male reproductive health.

背景:通信电磁辐射对男性生殖系统的影响已成为公共卫生领域的一个重大问题。与传统的 2G、3G 和 4G 频段相比,5G sub-6 GHz 频段的一个显著特点是包含了更高的频段。这引起了公众对这些较高频率对生物,尤其是其生殖系统的潜在影响的担忧。虽然必须在实验室环境中研究这些新频段的生物效应和潜在风险,但由于缺乏标准化参数(如暴露条件和持续时间),比较和评估不同频段之间的差异仍然具有挑战性。相比之下,剂量评估提供了一种更简单、更可靠的方法:本研究采用剂量评估法来调查 5G 基站产生的 6 GHz 以下电磁辐射对男性生殖系统的相关风险。利用经典人体模型(Duke),并根据暴露基站的实际极化方向和各种身体姿势建立电磁模拟环境。这项研究探讨了电场方向、姿势、公共人群和频率对生殖系统特定吸收率的影响:在保持相同暴露水平的情况下,频率越高,对生殖系统的剂量越小。进一步的分析表明,考虑到公众的暴露阈值,在 5G sub-6 GHz 中使用较高的频段与较低的频段相比,不会对生殖系统产生更大的剂量。因此,在剂量方面,公众无需过分担心 6 千兆赫以下 5G 基站发出的电磁辐射对男性生殖健康的影响。
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引用次数: 0
Sequential radiation exposure: uncovering the potential of low dose ionizing radiation in mitigating high dose effects on immune cells. 连续辐照:揭示低剂量电离辐射在减轻高剂量对免疫细胞影响方面的潜力。
Pub Date : 2024-01-01 Epub Date: 2024-05-22 DOI: 10.1080/09553002.2024.2345107
Sadegh Masoudi, Mehdi Kalani, Ali Alavianmehr, Mohammad Amin Mosleh-Shirazi, Seyed Mohammad Javad Mortazavi, Shirin Farjadian

Purpose: The radioadaptive response refers to a phenomenon wherein exposure to a low dose of ionizing radiation (LDIR) can induce a protective response in cells or organisms, reducing the adverse effects of a subsequent higher dose of ionizing radiation (HDIR). However, it is possible to administer the low dose after the challenge dose. This study was conducted to determine the potential mitigating effect of LDIR administered after HDIR on mice immune cells.

Materials and methods: Alongside the conventional adaptive response setting, one group of mice was initially exposed to HDIR and subsequently treated with LDIR. Neutrophil activation was done using DHR-reducing assay and cell proliferation was evaluated through CFSE-dilution assay in helper (CD4+) and cytotoxic (CD8+) T cells. Cytokine production by these T cell subsets was also assessed by intracellular staining using flow cytometry.

Results: The results of this study revealed no change in neutrophil function between any of the mice groups compared to the untreated control group. Although significant changes were not detected in the proliferation of CD4+ T cells, decreased proliferation was observed in stimulated CD8+ T cells in the HDIR group. In contrast to IFN-ɣ, which showed no evident change in either of the T cell subsets after stimulation, IL-4 was rigorously dropped in stimulated CD4+ T cells in the HDIR group.

Conclusions: In summary, the results of this study indicated that the administration of LDIR to mice before HDIR was not able to reduce the detrimental effects of HDIR in our experimental setting. Instead, we observed a mitigating effect of LDIR when administered after the challenge dose. This suggests that not only the dose and duration but also the order of LDIR relative to HDIR affects its efficacy.

目的:放射适应反应是指这样一种现象,即暴露于低剂量电离辐射(LDIR)可诱导细胞或生物体产生保护性反应,减少随后的高剂量电离辐射(HDIR)的不利影响。不过,可以在挑战剂量之后再施用低剂量。本研究旨在确定在高剂量电离辐射后施用低剂量电离辐射对小鼠免疫细胞的潜在缓解效应:除了传统的适应性反应设置,一组小鼠最初暴露于 HDIR,随后接受 LDIR 治疗。中性粒细胞活化是通过 DHR 还原试验进行的,细胞增殖是通过辅助性(CD4+)和细胞毒性(CD8+)T 细胞的 CFSE 稀释试验进行评估的。这些 T 细胞亚群产生的细胞因子也通过流式细胞术进行细胞内染色评估:研究结果表明,与未经处理的对照组相比,各组小鼠的中性粒细胞功能均无变化。虽然 CD4+ T 细胞的增殖未发现明显变化,但在 HDIR 组中,受刺激的 CD8+ T 细胞的增殖有所下降。IFN-ɣ在刺激后在两个 T 细胞亚群中均未显示出明显变化,与此形成对比的是,在 HDIR 组中,受刺激的 CD4+ T 细胞中的 IL-4 显著下降:总之,本研究结果表明,在我们的实验环境中,在 HDIR 之前给小鼠注射 LDIR 并不能减轻 HDIR 的有害影响。相反,我们观察到在挑战剂量后给予 LDIR 有缓解作用。这表明,不仅是剂量和持续时间,LDIR 相对于 HDIR 的顺序也会影响其疗效。
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引用次数: 0
Lifetime attributable risks (LARs) of cancer in the fetus associated with maternal radiography examinations. 与孕产妇放射检查相关的胎儿患癌终生归因风险(LARs)。
Pub Date : 2024-01-01 Epub Date: 2024-01-09 DOI: 10.1080/09553002.2023.2295294
Asra Sadat Talebi, Roghiyeh Bodaghi, Saeed Bagherzadeh

Purpose: For various reasons, pregnant women are occasionally exposed to ionizing radiation during radiology examinations. In these situations, it is essential to determine the radiation dose to the fetus and any associated risks. The present study attempts to calculate the mean dose for the fetus to estimate the possible cancer induction and cancer mortality risks resulting from maternal radiography exams.

Material and methods: The GATE Monte Carlo platform and a standard voxelized pregnant phantom were employed to calculate fetal radiation dose during maternal radiography exams. The data published in Biological Effects of Ionizing Radiation VII were used to convert fetal dose to lifetime attributable risks (LARs) of cancer incidence and cancer-related mortality.

Results: The fetal doses and LARs of cancer incidence and cancer-related mortality for the radiographs of the chest and skull were negligible. The maximum LAR values for the lateral view of the abdomen in computed and digital radiography are 5598.29 and 2238.95 per 100,000 individuals, respectively. The computed radiography of the lateral view of the abdomen revealed the highest LAR of cancer-related mortality (2074.30 deaths for every 100,000 people).

Conclusion: The radiation dose incurred by the fetus due to chest and skull radiographs was minimal and unlikely to cause any abnormalities in the fetus. The discernible elevation in the lifetime attributable risk associated with cancer incidence and mortality arising from lateral computed radiography examinations of the abdomen warrants careful consideration within the realm of maternal radiography examinations.

目的:由于各种原因,孕妇在接受放射检查时偶尔会受到电离辐射。在这种情况下,必须确定胎儿所受的辐射剂量及相关风险。本研究试图计算胎儿的平均剂量,以估算孕产妇放射检查可能导致的癌症诱发和癌症死亡风险:材料与方法:采用 GATE Monte Carlo 平台和标准体素化孕妇模型来计算孕产妇射线照相检查时的胎儿辐射剂量。采用《电离辐射的生物效应 VII》中公布的数据,将胎儿剂量转换为癌症发病率和癌症相关死亡率的终生归因风险(LARs):结果:胸部和颅骨射线照片的胎儿剂量和癌症发病率及癌症相关死亡率的 LAR 值可忽略不计。腹部侧视图的计算机和数字射线摄影的最大 LAR 值分别为每 10 万人 5598.29 和 2238.95。腹部侧视图的计算机射线摄影显示癌症相关死亡率的 LAR 值最高(每 10 万人中有 2074.30 人死亡):结论:胎儿因胸部和颅骨 X 射线照相而受到的辐射剂量极小,不太可能导致胎儿畸形。腹部侧位计算机放射摄影检查引起的与癌症发病率和死亡率相关的终生可归因风险的明显升高,值得在孕产妇放射摄影检查中仔细考虑。
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引用次数: 0
Validation of genes for H-ARS severity prediction in leukemia patients - interspecies comparison, challenges, and promises. 白血病患者 H-ARS 严重程度预测基因的验证 - 种间比较、挑战和前景。
Pub Date : 2024-01-01 Epub Date: 2024-01-16 DOI: 10.1080/09553002.2023.2295295
Daniel Schwanke, Marco Valente, Patrick Ostheim, Simone Schüle, Laure Bobyk, Michel Drouet, Diane Riccobono, Nicolas Magné, Elisabeth Daguenet, Samantha Jo Stewart, Razan Muhtadi, Matthias Port, Michael Abend

Purpose: In a previous baboon-study, a total of 29 genes were identified for clinical outcome prediction of the hematologic, acute, radiation, syndrome (H-ARS) severity. Among them, four genes (FDXR, DDB2, POU2AF1, WNT3) appeared promising and were validated in five leukemia patients. Within this study, we sought further in-vivo validation in a larger number of whole-body irradiated patients.

Material and methods: Peripheral blood was drawn from 10 leukemia patients before and up to 3 days during a fractionated (2 Gy/day) total-body irradiation (TBI) with 2-12Gy. After RNA-isolation, gene expression (GE) was evaluated on 31 genes widely used in biodosimetry and H-ARS prediction employing qRT-PCR. A customized low-density-array (LDA) allowed simultanously analyzing all genes, the 96-well format further examined the four most promising genes. Fold-changes (FC) in GE relative to pre-irradiation were calculated.

Results: Five patients suffering from acute-lymphoblastic-leukemia (ALL) respectively non-Hodgkin-lymphoma (NHL) revealed sufficient RNA-amounts and corresponding lymphocyte and neutrophile counts for running qRT-PCR, while acute-myeloid-leukemia (AML) and one myelofibrosis patient could not supply enough RNA. Generally, 1-2µg total RNA was isolated, whereas up to 10-fold differences in RNA-quantities (associated suppressed GE-changes) were identified among pre-exposure and exposure samples. From 31 genes, 23 were expressed in at least one of the pre-exposure samples. Relative to pre-exposure, the number of expressed genes could halve at 48 and 72h after irradiation. Using the LDA, 13 genes were validated in human samples. The four most promising genes (vid. sup.) were either undetermined or too close to pre-exposure. However, they were measured using the more sensitive 96-well format, except WNT3, which wasn´t detectable. As in previous studies, an opposite regulation in GE for FDXR in leukemia patients (up-regulated) relative to baboons (down-regulated) was reconfirmed. Radiation-induced GE-changes of DDB2 (up-regulated) and POU2AF1 (down-regulated) behaved similarly in both species. Hence, 16 out of 23 genes of two species showed GE-changes in the same direction, and up-regulated FDXR as in human studies were revalidated.

Conclusion: Identified genes for H-ARS severity prediction, previously detected in baboons, were validated in ALL but not in AML patients. Limitations related to leukemia type, associated reduced RNA amounts, suppressed GE changes, and methodological challenges must be considered as factors negatively affecting the total number of validated genes. Based on that, we propose additional controls including blood cell counts and preferably fluorescence-based RNA quantity measurements for selecting promising samples and using a more sensitive 96-well format for candidate genes with low baseline copy

目的:在之前的一项狒狒研究中,共发现了 29 个用于预测血液病、急性辐射综合征(H-ARS)严重程度的临床结果的基因。其中,有四个基因(FDXR、DDB2、POU2AF1、WNT3)很有希望,并在五名白血病患者中得到了验证。在本研究中,我们试图在更多的全身辐照患者中进一步进行体内验证:在对10名白血病患者进行2-12Gy的全身分次(2Gy/天)辐照(TBI)之前和辐照期间的3天内,抽取他们的外周血。在进行 RNA 分离后,采用 qRT-PCR 方法对广泛用于生物模拟和 H-ARS 预测的 31 个基因的基因表达(GE)进行了评估。定制的低密度阵列(LDA)可同时分析所有基因,96 孔格式进一步检查了四个最有希望的基因。计算了GE相对于辐照前的折叠变化(FC):结果:五名急性淋巴细胞白血病(ALL)患者和一名非霍奇金淋巴瘤(NHL)患者的RNA量以及相应的淋巴细胞和中性粒细胞计数足以进行qRT-PCR,而急性髓细胞白血病(AML)患者和一名骨髓纤维化患者无法提供足够的RNA。一般来说,分离到的 RNA 总量为 1-2 微克,而在暴露前和暴露后的样本中,发现 RNA 数量最多相差 10 倍(相关的抑制基因变化)。在 31 个基因中,23 个基因在至少一个暴露前样本中表达。与辐照前相比,辐照后 48 小时和 72 小时表达基因的数量可能减少一半。利用 LDA,13 个基因在人体样本中得到了验证。其中最有希望的四个基因(参见上图)要么尚未确定,要么与辐照前太过接近。不过,除了无法检测到的 WNT3 外,它们都是用灵敏度更高的 96 孔格式检测的。与之前的研究一样,白血病患者(上调)与狒狒(下调)的 FDXR 的 GE 调节相反,这一点再次得到证实。辐射诱导的 DDB2(上调)和 POU2AF1(下调)的 GE 变化在两个物种中表现相似。因此,在两个物种的23个基因中,16个基因的GE变化方向相同,人类研究中上调的FDXR得到了重新验证:结论:先前在狒狒中发现的用于预测H-ARS严重程度的基因在ALL患者中得到了验证,但在AML患者中未得到验证。与白血病类型有关的局限性、相关的 RNA 量减少、GE 变化受抑制以及方法学上的挑战必须被视为对验证基因总数产生负面影响的因素。在此基础上,我们建议进行更多的控制,包括血细胞计数和基于荧光的 RNA 数量测量,以选择有希望的样本,并使用更灵敏的 96 孔格式来检测基线拷贝数较低的候选基因。
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引用次数: 0
Association between radiation dose, thyroid hormone, and IQ levels in children exposed to radiation in utero after the Chernobyl accident. 切尔诺贝利核电站事故后子宫内受辐射儿童的辐射剂量、甲状腺激素和智商水平之间的关系。
Pub Date : 2024-01-01 Epub Date: 2024-05-15 DOI: 10.1080/09553002.2024.2345088
Liudmila Liutsko, Sergey Igumnov, Vladimir Drozdovitch, Elisabeth Cardis

Few studies have explored the effects of n utero radiation exposure on human health and cognition and none have taken into account thyroid hormone levels (T3), which have shown to affect cognitive performance. We investigated mechanisms of possible radiation effects on IQ in two cohorts of 250 persons each: exposed n utero after the Chernobyl accident: a 'higher exposure group (HEG)', whose mothers resided in more heavily contaminated territories at the time of the Chernobyl accident, and a 'lesser exposure group (LEG)' whose mothers resided in less contaminated areas. The dataset included information on estimated prenatal thyroid radiation dose, gestation week at the time of the accident (ATA); thyroid hormones: T3 (triiodothyronine) and T4 (thyroxine) levels measured at age 11-12 years and general IQ measured at three time points: t1: 6-7 years old; t2: 11-12 years old and t3: 15-16 years old. Descriptive and inference analyses were used to explore the dynamic of changes through time and the associations between key variables at the three time points. Estimated radiation doses to the thyroid gland were substantially higher in the HEG than in the LEG (mean 391 vs 25 mGy respectively). Significant differences in thyroid hormones levels were observed between the two groups, with lower values in T3 (higher in T4) in the LEG. At t1, the general IQ, as well as verbal and non-verbal IQ scores, were lower in the HEG than in the LEG. In the HEG, analyses adjusting simultaneously for radiation dose, gestational week ATA and T3 levels suggest that all three variables are associated with IQ, with the latter being highest among those exposed later during gestation and decreasing with increasing level of dose and of T3. No significant association was observed between IQ and T4 levels. No effect of exposure on IQ was seen in the LEG. Further investigation of this hypothesis will be important to understand the relation between n utero exposure radiation dose to thyroid, thyroid hormone levels and IQ, taking into account effects of potential confounding factors (physiological stress, maternal anxiety related evacuation).

很少有研究探讨子宫内辐照对人类健康和认知能力的影响,也没有研究考虑到甲状腺激素水平(T3),而甲状腺激素水平已被证明会影响认知能力。我们研究了切尔诺贝利事故后子宫内辐照对智商可能产生影响的两个组群,每个组群 250 人:一个是 "高辐照组(HEG)",其母亲在切尔诺贝利事故发生时居住在污染较严重的地区;另一个是 "低辐照组(LEG)",其母亲居住在污染较轻的地区。数据集包括估计的产前甲状腺辐射剂量、事故发生时的妊娠周数(ATA)、甲状腺激素、T3(三碘甲状腺原氨酸在 11-12 岁时测量的 T3(三碘甲状腺原氨酸)和 T4(甲状腺素)水平,以及在三个时间点测量的一般智商:第一时间点:6-7 岁;第二时间点:11-12 岁;第三时间点:15-16 岁。通过描述性分析和推理分析来探讨三个时间点的动态变化以及关键变量之间的关联。甲状腺受到的估计辐射剂量在 HEG 中远高于 LEG(平均值分别为 391 mGy 和 25 mGy)。两组之间的甲状腺激素水平存在显著差异,专家组的 T3 值较低,而 T4 值较高。在 t1 期,HEG 的一般智商以及言语和非言语智商得分均低于 LEG。在 HEG 中,同时调整辐射剂量、孕周 ATA 和 T3 水平的分析表明,这三个变量都与智商有关,后者在妊娠晚期受辐射者中最高,并随着剂量和 T3 水平的增加而降低。在智商和 T4 水平之间没有观察到明显的关联。专家组没有发现暴露对智商的影响。要了解子宫内甲状腺辐射剂量、甲状腺激素水平和智商之间的关系,并考虑到潜在混杂因素(生理压力、与撤离有关的产妇焦虑)的影响,对这一假设的进一步研究将非常重要。
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引用次数: 0
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International journal of radiation biology
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