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Main radiation pathways in the landscape of Armenia. 亚美尼亚境内的主要辐射路径。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 DOI: 10.1080/09553002.2023.2172623
V B Arakelyan, G E Khachatryan, A G Nalbandyan-Schwarz, C E Mothersill, C B Seymour, V L Korogodina

Purpose: To investigate sources, accumulation, and vertical migration of radionuclides in Armenia, and their impact on biota.

Conclusions: This review describes the radiation status in the landscape of Armenia and features of the impact of natural and human-generated radiation on human and non-human biotas, according to studies of Armenian scientists carried out since the middle of the last century. The mountain landscape demonstrates the diversity, speciation, and radioresistance of the biota, which arise under radiation exposure in a variable environment. Although the effects of radiation have been described for a long time, some of them require further study. It is important to present the data collected in order to produce a base line for future studies of radiation effects and interactions with other stressors caused by climate change.

目的:了解亚美尼亚放射性核素的来源、积累、垂直迁移及其对生物群的影响。结论:根据上世纪中叶以来亚美尼亚科学家开展的研究,本综述描述了亚美尼亚景观中的辐射状况以及自然和人为产生的辐射对人类和非人类生物的影响特征。山区景观表现出多样性、物种形成和生物群的抗辐射性,这些生物群是在不同环境的辐射照射下产生的。虽然辐射的影响已经被描述了很长时间,但其中一些还需要进一步研究。必须提出所收集的数据,以便为今后研究气候变化引起的辐射效应和与其他压力源的相互作用提供基线。
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引用次数: 0
Limiting exposure to radiofrequency radiation: the principles and possible criteria for health protection. 限制暴露于射频辐射:健康保护的原则和可能的标准。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 Epub Date: 2023-01-03 DOI: 10.1080/09553002.2023.2159567
Hiie Hinrikus, Tarmo Koppel, Jaanus Lass, Priit Roosipuu, Maie Bachmann

Purpose: The current paper is aimed to discuss the principles and criteria for health protection to radiofrequency electromagnetic field (RF EMF) considering both thermal and non-thermal mechanisms to evaluate the reasonable level for the limits relevant to control the level of RF EMF for the general public in the living environment. The study combines the conclusions of analyses published in recent reviews on RF EMF effects and the data from RF EMF measurements in different countries to select the possible criteria and to derive proposals for the health protection limits on the level of RF EMF following the ALARA principle - as low as reasonably achievable.

Conclusions: Consideration of not only energetic but also coherent qualities of RF EMF leads to two different models for determining the impact of non-ionizing radiation on human health. The thermal model, based on absorption of electromagnetic energy, has a threshold limiting the heating of tissues. The non-thermal model, based on the ability of coherent electric fields to introduce biological effects at constant temperature, has no threshold. Therefore, the impact of RF EMF on human health cannot be excluded but can be minimized by limiting the level of the radiation. The limits can be selected based on indirect criteria. The minimal level of RF EMF that has caused a biological effect is about 2 V/m. The level of long-term broadcast radiation is 6 V/m and the people can be assumed to be adapted to that level without observable health problems. The level of RF EMF measured during last years does not exceed 5 V/m and the level is decreasing with newer generations of telecommunication technology. Limiting the level of RF EMF to the peak value of 6 V/m hopefully reduces the health risk to a minimal level people are adapted to and does not restrict the further development of telecommunication technology.

目的:本文旨在讨论射频电磁场(RF EMF)健康保护的原则和标准,同时考虑热机制和非热机制,以评估生活环境中普通公众控制RF EMF水平的合理限值水平。该研究结合了最近发表的关于RF EMF影响的综述中的分析结论和不同国家的RF EMF测量数据,以选择可能的标准,并根据ALARA原则得出RF EMF水平的健康保护限制建议——尽可能低。结论:考虑到RF EMF的能量和相干性质,产生了两种不同的模型来确定非电离辐射对人类健康的影响。基于电磁能吸收的热模型具有限制组织加热的阈值。基于相干电场在恒定温度下引入生物效应的能力的非热模型没有阈值。因此,不能排除RF EMF对人类健康的影响,但可以通过限制辐射水平将其降至最低。可以根据间接标准选择限制。已经引起生物效应的RF EMF的最小水平是大约2V/m。长期广播辐射水平为6V/m,可以假设人们适应了这个水平,没有明显的健康问题。在过去几年中测量的RF EMF水平不超过5V/m,并且随着新一代电信技术的发展,该水平正在下降。将RF EMF的水平限制在6V/m的峰值有望将健康风险降低到人们适应的最小水平,并且不会限制电信技术的进一步发展。
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引用次数: 1
Summary of Radiation Research Society Online 67th Annual Meeting, Symposium on "Radiation and Circulatory Effects". 辐射研究学会第67届在线年会“辐射与循环效应”研讨会纪要。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2110304
Helmut Schöllnberger, Lawrence T Dauer, Richard Wakeford, Julie Constanzo, Ashley Golden

Purpose: This article summarizes a number of presentations from a session on "Radiation and Circulatory Effects" held during the Radiation Research Society Online 67th Annual Meeting, October 3-6 2021.

Materials and methods: Different epidemiological cohorts were analyzed with various statistical means common in epidemiology. The cohorts included the one from the U.S. Million Person Study and the Canadian Fluoroscopy Cohort Study. In addition, one of the contributions in our article relies on results from analyses of the Japanese atomic bomb survivors, Russian emergency and recovery workers and cohorts of nuclear workers. The Canadian Fluoroscopy Cohort Study data were analyzed with a larger series of linear and nonlinear dose-response models in addition to the linear no-threshold (LNT) model.

Results and conclusions: The talks in this symposium showed that low/moderate acute doses at low/moderate dose rates can be associated with an increased risk of CVD, although some of the epidemiological results for occupational cohorts are equivocal. The usually only limited availability of information on well-known risk factors for circulatory disease (e.g. smoking, obesity, hypertension, diabetes, physical activity) is an important limiting factor that may bias any observed association between radiation exposure and detrimental health outcome, especially at low doses. Additional follow-up and careful dosimetric and outcome assessment are necessary and more epidemiological and experimental research is required. Obtaining reliable information on other risk factors is especially important.

目的:本文总结了2021年10月3日至6日在辐射研究学会在线第67届年会上举行的“辐射和循环效应”会议上的一些演讲。材料与方法:采用流行病学常用的各种统计方法对不同的流行病学队列进行分析。队列包括来自美国百万人研究和加拿大透视队列研究的队列。此外,我们文章中的一项贡献依赖于对日本原子弹幸存者、俄罗斯紧急和恢复工作人员以及核工作人员群体的分析结果。加拿大透视队列研究数据除线性无阈值(LNT)模型外,还采用了一系列更大的线性和非线性剂量反应模型进行分析。结果和结论:本次研讨会的讨论表明,低/中等急性剂量和低/中等剂量率可能与CVD风险增加有关,尽管职业队列的一些流行病学结果是模棱两可的。关于众所周知的循环系统疾病风险因素(如吸烟、肥胖、高血压、糖尿病、体育活动)的信息通常有限,这是一个重要的限制因素,可能会影响已观察到的辐射照射与有害健康结果之间的关联,特别是在低剂量下。需要进一步的随访和仔细的剂量学和结果评估,并需要进行更多的流行病学和实验研究。获得关于其他风险因素的可靠信息尤其重要。
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引用次数: 3
Is micronucleus assay a suitable method for biomonitoring children exposed to X-ray? A systematic review with meta-analysis. 微核试验是一种适合于对暴露于X射线的儿童进行生物监测的方法吗?荟萃分析系统综述。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 Epub Date: 2023-03-31 DOI: 10.1080/09553002.2023.2194405
Ingra Tais Malacarne, Wilton Mitsunari Takeshita, Milena de Barros Viana, Ana Claudia Muniz Renno, Daniel Araki Ribeiro

Purpose: The aim of this study was to evaluate if the micronucleus test using oral epithelial cells is a suitable biomarker for biomonitoring children exposed to X-ray.

Material and methods: A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to February 2022 that examined the relationship between exposure of children to radiographic examinations and micronucleus.

Results: A total of 17 full-text manuscripts were screened for eligibility. Only two studies found a difference in micronucleus labeling. On the other hand, all studies showed that X-ray was able to induce cellular death in oral mucosa cells. Following the parameters of the Effective Practices in Public Health Project (EPHPP), five manuscripts reached moderate and strong scores, and four studies were categorized as weak at final rating. In the meta-analysis, statistically significant difference was detected in micronucleated cells in children before and after radiographic examinations (SMD = 0.96, 95% CI, 0.07-1.84, p = .04), with τ2=1.09; χ2=53.37, and p < .001.

Conclusion: Radiographic examinations in children can cause genotoxic and cytotoxic damage in the oral epithelium with a large effect size.

目的:本研究的目的是评估使用口腔上皮细胞的微核试验是否是一种适合于对暴露于X射线的儿童进行生物监测的生物标志物。材料和方法:通过电子数据库PubMed/Medline、Scopus和Web of Science进行搜索,截至2022年2月发表的所有研究都检验了儿童暴露于射线照相检查与微核之间的关系。结果:共筛选出17篇全文稿件。只有两项研究发现微核标记存在差异。另一方面,所有研究都表明,X射线能够诱导口腔粘膜细胞的细胞死亡。根据公共卫生有效实践项目(EPHPP)的参数,有五份手稿达到了中等和较强的分数,四项研究在最终评级中被归类为较弱。在荟萃分析中,儿童放射检查前后的微核细胞存在统计学显著差异(SMD=0.96,95%CI,0.07-1.84,p = .04),其中τ2=1.09;χ2=53.37,p 结论:儿童X线检查可引起口腔上皮细胞的遗传毒性和细胞毒性损伤,影响范围较大。
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引用次数: 0
Protective mechanism of a novel aminothiol compound on radiation-induced intestinal injury. 一种新型氨基硫醇化合物对辐射引起的肠道损伤的保护机制。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2074163
Xinxin Wang, Renbin Yuan, Longfei Miao, Xuejiao Li, Yuying Guo, Hongqi Tian

Purpose: With the development of nuclear technology and radiotherapy, the risk of radiation injury has been increasing. Therefore, it is important to find an effective radiation-protective agent. In this study, we designed and synthesized a novel compound called compound 8, of which the radioprotective effect and mechanism were studied.

Materials and methods: Before being exposed to ionizing radiation, mice were pretreated with compound 8. The 30-day mortality assay, hematoxylin-eosin staining, and immunohistochemistry staining assay were performed to evaluate the anti-radiation effect of the compound 8. TUNEL and immunofluorescence assays were conducted to study the anti-radiation mechanism of compound 8.

Results: Compared to the IR + vehicle group, the 30-day survival rate of mice treated with 25 mg/kg of compound 8 was significantly improved after 8 Gy total body irradiation. In the morphological study of the small intestine, we found that compound 8 could maintain crypt-villus structures in the irradiated mice. Further immunohistochemical staining displayed that compound 8 could improve the survival of Lgr5+ cells, ki67+ cells, and lysozyme+ cells. The results of TUNEL and immunofluorescence assays showed that compound 8 could decrease the expression of apoptosis-related caspase-8/-9, γ-H2AX, Bax, and p53.

Conclusions: These results indicate that compound 8 exerts its effects by maintaining structure and function of small intestine. It also reduces DNA damage, promotes crypt proliferation and differentiation. Moreover, it may enhance the anti-apoptotic ability of small intestinal tissue by inhibiting the activation of p53 and blocking the caspase cascade reaction. Compound 8 can protect the intestinal tract from post-radiation damage, it is thus a new and effective protective agent of radiation.

目的:随着核技术和放射治疗的发展,放射损伤的风险不断增加。因此,寻找一种有效的防辐射剂非常重要。在本研究中,我们设计并合成了一种名为化合物8的新化合物,并对其辐射防护作用和机理进行了研究。材料与方法:小鼠在电离辐射前用化合物8进行预处理。采用30天死亡率测定、苏木精-伊红染色、免疫组化染色评价化合物8的抗辐射作用。采用TUNEL和免疫荧光法研究化合物8的抗辐射作用机制。结果:与IR +载药组相比,化合物8 25 mg/kg全身照射后小鼠30天存活率明显提高。在小肠形态学研究中,我们发现化合物8能维持受辐射小鼠的隐窝绒毛结构。进一步免疫组化染色显示化合物8能提高Lgr5+细胞、ki67+细胞和溶菌酶+细胞的存活率。TUNEL和免疫荧光检测结果显示,化合物8可降低凋亡相关caspase-8/-9、γ-H2AX、Bax和p53的表达。结论:化合物8通过维持小肠结构和功能发挥作用。它还能减少DNA损伤,促进隐窝增殖和分化。此外,它可能通过抑制p53的激活和阻断caspase级联反应来增强小肠组织的抗凋亡能力。化合物8具有保护肠道免受辐射后损伤的作用,是一种新型有效的辐射保护剂。
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引用次数: 2
Investigation of radiation protective features of azadispiro derivatives and their genotoxic potential with Ames/Salmonella test system. 用Ames/沙门氏菌检测系统研究阿扎皮罗衍生物的辐射防护特性及其基因毒性。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2087930
Burak Alaylar, Bünyamin Aygün, Kadir Turhan, Mehmet Karadayı, Esra Cinan, Zuhal Turgut, Gökçe Karadayı, Mohammed Ibrahim Abu Al-Sayyed, Medine Güllüce, Abdulhalik Karabulut

Purpose: Five different types of synthesized azadispiro derivatives have been analyzed for radiation absorption capacity and determined their potential to be exploited as substances for a drug to be developed against radiation has been investigated.

Material and methods: Fast neutron attenuation parameters like the effective mean free path, half-value layer (HVL), removal cross-sections, and neutron transmission number were found with the Monte Carlo simulation Geometry And Tracking (GEANT4) code. Gamma radiation absorption parameters, such as effective atom number (Zeff), mean free path (MFP), mass attenuation coefficient (MAC), and half-value layer (HVL) were theoretically determined with WinXCom software. Besides, the exposure build-up factor (EBF) was calculated by using GP fitting parameters. Neutron absorption dose rate was experimentally calculated with 241Am-Be fast neutron source which has 4.5 MeV of energy, 74 GBq activity, and portative BF3 neutron detector. Ames/Salmonella test systems were used for the genotoxic potentials of the azadispiro derivatives.

Results and conclusions: Experimental and theoretical results were checked with paraffin and High-Density Polyethylene. The results showed that Azadispiro derivatives have neutron radiation absorption capability close to paraffin and High-Density Polyethylene. The gamma radiation absorption properties for azadispiro derivatives have been investigated, and it has been observed that these materials can absorb gamma radiation. Ames/Salmonella assay was used to examine whether the derivatives had a genotoxic effect probability or not. The results showed that these derivatives were genotoxic and safe at test doses (up to 5 mM). Consequently, it has been understood that these azadispiro derivatives can be used as active and genotoxic safety ingredients in the production of a protective drug against both neutrons and gamma rays.

目的:分析了五种不同类型的合成azadispiro衍生物的辐射吸收能力,并确定了它们作为抗辐射药物开发物质的潜力。材料与方法:利用Monte Carlo simulation Geometry and Tracking (GEANT4)程序计算快中子衰减参数,如有效平均自由程、半值层(HVL)、去除截面、中子透射数等。利用WinXCom软件对有效原子序数(Zeff)、平均自由程(MFP)、质量衰减系数(MAC)、半值层(HVL)等γ辐射吸收参数进行理论测定。此外,利用GP拟合参数计算暴露累积因子(EBF)。利用能量为4.5 MeV、活度为74 GBq的241Am-Be快中子源和便携式BF3中子探测器,实验计算了中子吸收剂量率。采用Ames/沙门氏菌检测系统检测阿扎皮罗衍生物的遗传毒性。结果与结论:用石蜡和高密度聚乙烯对实验和理论结果进行了验证。结果表明,Azadispiro衍生物具有接近石蜡和高密度聚乙烯的中子辐射吸收能力。研究了azadispiro衍生物对γ辐射的吸收特性,发现这些材料可以吸收γ辐射。采用Ames/沙门氏菌法检测衍生物是否具有遗传毒性作用概率。结果表明,这些衍生物在试验剂量(高达5 mM)下具有遗传毒性和安全性。因此,人们已经认识到,这些azadispiro衍生物可以作为活性和遗传毒性的安全成分,用于生产抗中子和伽马射线的保护药物。
{"title":"Investigation of radiation protective features of azadispiro derivatives and their genotoxic potential with Ames/<i>Salmonella</i> test system.","authors":"Burak Alaylar,&nbsp;Bünyamin Aygün,&nbsp;Kadir Turhan,&nbsp;Mehmet Karadayı,&nbsp;Esra Cinan,&nbsp;Zuhal Turgut,&nbsp;Gökçe Karadayı,&nbsp;Mohammed Ibrahim Abu Al-Sayyed,&nbsp;Medine Güllüce,&nbsp;Abdulhalik Karabulut","doi":"10.1080/09553002.2022.2087930","DOIUrl":"https://doi.org/10.1080/09553002.2022.2087930","url":null,"abstract":"<p><strong>Purpose: </strong>Five different types of synthesized azadispiro derivatives have been analyzed for radiation absorption capacity and determined their potential to be exploited as substances for a drug to be developed against radiation has been investigated.</p><p><strong>Material and methods: </strong>Fast neutron attenuation parameters like the effective mean free path, half-value layer (HVL), removal cross-sections, and neutron transmission number were found with the Monte Carlo simulation Geometry And Tracking (GEANT4) code. Gamma radiation absorption parameters, such as effective atom number (<i>Z</i><sub>eff</sub>), mean free path (MFP), mass attenuation coefficient (MAC), and half-value layer (HVL) were theoretically determined with WinXCom software. Besides, the exposure build-up factor (EBF) was calculated by using GP fitting parameters. Neutron absorption dose rate was experimentally calculated with <sup>241</sup>Am-Be fast neutron source which has 4.5 MeV of energy, 74 GBq activity, and portative BF<sub>3</sub> neutron detector. Ames<i>/Salmonella</i> test systems were used for the genotoxic potentials of the azadispiro derivatives.</p><p><strong>Results and conclusions: </strong>Experimental and theoretical results were checked with paraffin and High-Density Polyethylene. The results showed that Azadispiro derivatives have neutron radiation absorption capability close to paraffin and High-Density Polyethylene. The gamma radiation absorption properties for azadispiro derivatives have been investigated, and it has been observed that these materials can absorb gamma radiation. Ames/<i>Salmonella</i> assay was used to examine whether the derivatives had a genotoxic effect probability or not. The results showed that these derivatives were genotoxic and safe at test doses (up to 5 mM). Consequently, it has been understood that these azadispiro derivatives can be used as active and genotoxic safety ingredients in the production of a protective drug against both neutrons and gamma rays.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":"99 2","pages":"245-258"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9294684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Increased glucose influx and glycogenesis in lung cancer cells surviving after irradiation. 照射后存活的肺癌细胞中葡萄糖内流和糖生成增加。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2113837
Avgi Tsolou, Dimitrios Koparanis, Ioannis Lamprou, Alexandra Giatromanolaki, Michael I Koukourakis

Purpose: Lung cancer is considered as one of the most frequent malignancies worldwide. Radiotherapy is the main treatment modality applied for locally advanced disease, but remnant surviving cancer tissue results in disease progression in the majority of irradiated lung carcinomas. Metabolic reprogramming is regarded as a cancer hallmark and is associated with resistance to radiation therapy. Here, we explored metabolic alterations possibly related to cancer cell radioresistance.

Materials and methods: We compared the expression of metabolism-related enzymes in the parental A549 lung cancer cell line along with two new cell lines derived from A549 cells after recovery from three (A549-IR3) and six (A549-IR6) irradiation doses with 4 Gy. Differential GLUT1 and GYS1 expression on proliferation and radioresistance were also comparatively investigated.

Results: A549-IR cells displayed increased extracellular glucose absorption, and enhanced mRNA and protein levels of the GLUT1 glucose transporter. GLUT1 inhibition with BAY-876, suppressed cell proliferation and the effect was significantly more profound on A549-IR3 cells. Protein levels of molecules associated with aerobic or anaerobic glycolysis, or the phosphate pentose pathway were similar in all three cell lines. However, glycogen synthase 1 (GYS1) was upregulated, especially in the A549-IR3 cell line, suggestive of glycogen accumulation in cells surviving post irradiation. GYS1-gene silencing repressed the proliferation capacity of A549, but this increased their radioresistance. The radio-protective effect of the suppression of proliferative activity induced by GYS1 silencing did not protect A549-IR3 cells against further irradiation.

Conclusions: These findings indicate that GYS1 activity is a critical component of the metabolism of lung cancer cells surviving after fractionated radiotherapy. Targeting the glycogen metabolic reprogramming after irradiation may be a valuable approach to pursue eradication of the post-radiotherapy remnant of disease.

目的:肺癌是世界上最常见的恶性肿瘤之一。放射治疗是局部晚期疾病的主要治疗方式,但在大多数辐照后的肺癌中,残留的癌组织导致疾病进展。代谢重编程被认为是癌症的标志,并与放射治疗的耐药性有关。在这里,我们探索了可能与癌细胞放射抗性相关的代谢改变。材料和方法:我们比较了亲本A549肺癌细胞系和A549细胞在3次(A549- ir3)和6次(A549- ir6) 4 Gy照射后恢复的2个新细胞系中代谢相关酶的表达。GLUT1和GYS1的差异表达对细胞增殖和辐射抗性的影响也进行了比较研究。结果:A549-IR细胞显示细胞外葡萄糖吸收增加,GLUT1葡萄糖转运蛋白mRNA和蛋白水平升高。BAY-876抑制GLUT1可抑制细胞增殖,且对A549-IR3细胞的抑制作用更为显著。在所有三种细胞系中,与有氧或无氧糖酵解或磷酸戊糖途径相关的分子蛋白水平相似。然而,糖原合成酶1 (GYS1)上调,特别是在A549-IR3细胞系中,提示辐照后存活的细胞中糖原积累。gys1基因的沉默抑制了A549的增殖能力,但增加了它们的辐射抗性。GYS1沉默诱导的增殖活性抑制的放射保护作用不能保护A549-IR3细胞免受进一步的辐照。结论:这些发现表明GYS1活性是肺癌细胞分次放疗后存活代谢的关键组成部分。针对放射后糖原代谢重编程可能是一种有价值的方法,以追求根除放射后疾病的残余。
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引用次数: 2
Hormonal changes resulting from transgender conversion therapy may represent a gap in the biological effects of radiation understanding. 转基因转化治疗引起的激素变化可能代表了对辐射生物学效应的理解存在差距。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 Epub Date: 2023-05-11 DOI: 10.1080/09553002.2023.2211147
Edson R Andrade
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引用次数: 0
2-deoxy-D-glucose mitigates Citrobacter rodentium and dibenzazepine-induced gastrointestinal damage and colitis: novel implications of 2-DG polypharmacopea. 2-脱氧-d -葡萄糖减轻啮齿柠檬酸杆菌和二苯氮平诱导的胃肠道损伤和结肠炎:2-DG多药典的新意义。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2110297
Ishfaq Ahmed, Amit Verma, Shahid Umar, Rao V L Papineni
Abstract Purpose Citrobacter rodentium (CR) infection coupled with blocking Notch/Wnt signaling via γ-secretase inhibitor dibenzazepine (DBZ) disrupts the gastro-intestinal (GI) barrier and induces colitis, akin to ionizing radiation (IR)-induced GI-injury. We investigated the effects of 2-deoxy-D-glucose (2-DG) to ameliorate the CR-DBZ-induced GI damage. Materials and methods NIH:Swiss outbred mice were inoculated with 109CFUs of CR orally. DBZ was administered intraperitoneally (10 μM/kg b.wt; for 10 days 2 days post-CR infection). Mice were fed with 0.4% 2-DG (w/v) daily in drinking water. For microbiota depletion, antibiotics (Abx), 1 g/l metronidazole, and 0.2 g/l ciprofloxacin were administered for 10 days in drinking water. Oxidative stress, survival assay, colonic crypt hyperplasia, Notch/Wnt downstream signaling, immunomodulation, and bacterial dysbiosis were measured. Results We show that real-time visualization of reactive oxygen species (ROS) is similar during CR-induced colonic infection and IR-induced GI-damage. The histology revealed that dietary 2-DG mitigates CR + DBZ-induced colitis and improves survival compared with CR + DBZ alone. These changes were phenocopied in Abx-treated mice. Both 2-DG and Abx reduced dysbiosis, increased proliferation, inhibited pro-inflammatory response, and restored Hes-1 and β-catenin protein levels, in the crypts. Conclusion The energy disruptor 2-DG mitigates bacterial infection and its responsive hyperplasia/colitis, indicating its utility as a mitigator of infection/IR-induced GI-damage.
目的:鼠Citrobacter rodentium (CR)感染通过γ-分泌酶抑制剂二苯二氮平(DBZ)阻断Notch/Wnt信号通路,破坏胃肠道(GI)屏障并诱导结肠炎,类似于电离辐射(IR)诱导的GI损伤。我们研究了2-脱氧-d -葡萄糖(2-DG)对cr - dbz诱导的GI损伤的改善作用。材料与方法:采用美国国立卫生研究院(NIH):瑞士近交系小鼠口服接种109CFUs CR。腹腔注射DBZ (10 μM/kg b.wt);持续10天(cr感染后2天)。小鼠每天在饮用水中添加0.4% 2-DG (w/v)。为了减少微生物群,在饮用水中给予抗生素(Abx)、甲硝唑1 g/l、环丙沙星0.2 g/l,连续10天。测量氧化应激、存活测定、结肠隐窝增生、Notch/Wnt下游信号、免疫调节和细菌生态失调。结果:我们发现cr诱导的结肠感染和ir诱导的gi损伤期间活性氧(ROS)的实时可视化是相似的。组织学显示,与单独使用CR + DBZ相比,饲粮2-DG可减轻CR + DBZ诱导的结肠炎,提高生存率。这些变化在经abx治疗的小鼠中表现出来。2-DG和Abx均可减少隐窝内的生态失调,增加增殖,抑制促炎反应,恢复Hes-1和β-连环蛋白水平。结论:能量干扰物2-DG可减轻细菌感染及其反应性增生/结肠炎,表明其可减轻感染/ ir诱导的gi损伤。
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引用次数: 2
The intercellular communications mediating radiation-induced bystander effects and their relevance to environmental, occupational, and therapeutic exposures. 介导辐射诱导的旁观者效应的细胞间通信及其与环境、职业和治疗辐照的相关性。
IF 2.6 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-05-27 DOI: 10.1080/09553002.2022.2078006
Manuela Buonanno, Géraldine Gonon, Badri N Pandey, Edouard I Azzam

Purpose: The assumption that traversal of the cell nucleus by ionizing radiation is a prerequisite to induce genetic damage, or other important biological responses, has been challenged by studies showing that oxidative alterations extend beyond the irradiated cells and occur also in neighboring bystander cells. Cells and tissues outside the radiation field experience significant biochemical and phenotypic changes that are often similar to those observed in the irradiated cells and tissues. With relevance to the assessment of long-term health risks of occupational, environmental and clinical exposures, measurable genetic, epigenetic, and metabolic changes have been also detected in the progeny of bystander cells. How the oxidative damage spreads from the irradiated cells to their neighboring bystander cells has been under intense investigation. Following a brief summary of the trends in radiobiology leading to this paradigm shift in the field, we review key findings of bystander effects induced by low and high doses of various types of radiation that differ in their biophysical characteristics. While notable mechanistic insights continue to emerge, here the focus is on the many means of intercellular communication that mediate these effects, namely junctional channels, secreted molecules and extracellular vesicles, and immune pathways.

Conclusions: The insights gained by studying radiation bystander effects are leading to a basic understanding of the intercellular communications that occur under mild and severe oxidative stress in both normal and cancerous tissues. Understanding the mechanisms underlying these communications will likely contribute to reducing the uncertainty of predicting adverse health effects following exposure to low dose/low fluence ionizing radiation, guide novel interventions that mitigate adverse out-of-field effects, and contribute to better outcomes of radiotherapeutic treatments of cancer. In this review, we highlight novel routes of intercellular communication for investigation, and raise the rationale for reconsidering classification of bystander responses, abscopal effects, and expression of genomic instability as non-targeted effects of radiation.

目的:电离辐射穿过细胞核是诱发遗传损伤或其他重要生物反应的先决条件,但这一假设受到了研究的质疑,研究表明氧化改变超出了受辐照细胞的范围,也发生在邻近的旁观者细胞中。辐射场外的细胞和组织经历了显著的生化和表型变化,这些变化往往与在受辐照细胞和组织中观察到的变化相似。在评估职业、环境和临床辐照的长期健康风险方面,在旁观者细胞的后代中也检测到了可测量的遗传、表观遗传和代谢变化。氧化损伤如何从受辐照的细胞扩散到邻近的旁观者细胞一直是人们研究的重点。在简要总结了导致该领域范式转变的放射生物学趋势之后,我们回顾了低剂量和高剂量各种辐射诱导的旁观者效应的主要发现,这些辐射的生物物理特征各不相同。虽然显著的机理认识仍在不断涌现,但这里的重点是介导这些效应的多种细胞间通信方式,即连接通道、分泌分子和细胞外囊泡以及免疫途径:通过研究辐射的旁观者效应,人们对正常组织和癌组织在轻度和严重氧化应激下发生的细胞间通讯有了基本的了解。了解这些交流的基本机制可能有助于减少预测低剂量/低通量电离辐射照射后对健康产生不良影响的不确定性,指导减轻场外不良影响的新型干预措施,并有助于提高癌症放射治疗的效果。在这篇综述中,我们强调了有待研究的新型细胞间通信途径,并提出了重新考虑将旁观者反应、缺席效应和基因组不稳定性表达归类为辐射非靶效应的理由。
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引用次数: 3
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International Journal of Radiation Biology
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