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Effects of radiation on respiratory disease mortality: analysis of the national registry for radiation workers in United Kingdom. 辐射对呼吸系统疾病死亡率的影响:对英国辐射工作者国家登记的分析。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2023-01-01 Epub Date: 2023-03-15 DOI: 10.1080/09553002.2023.2187474
Wei Zhang, Richard G E Haylock, Michael Gillies, Nezahat Hunter, Erica Zhang

Purpose: While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK.

Materials and methods: The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases).

Results: There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= -0.56, 95%CI: -0.94, -0.06; p = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= -0.59, 95%CI: -0.99, -0.05; p = .017) but not significant among the workers who were not monitored (ERR/Sv= -0.43, 95%CI: -1.20, 0.74; p = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: -0.82, 5.65; p = .25).

Conclusion: The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.

目的:虽然现在已经出现了一些证据表明低剂量辐射暴露对呼吸道疾病有影响,但不同研究和国家之间的风险存在异质性。本文旨在通过对英国NRRW队列的分析,展示辐射对三种不同亚型呼吸系统疾病死亡率的影响。材料和方法:NRRW人群由174541名辐射工作者组成。使用单独的胶片徽章监测身体表面的剂量。大多数剂量与X射线和伽马射线有关,β和中子粒子的剂量较少。总体平均10年滞后寿命外部剂量为23.2 mSv。一些工人可能接触到阿尔法粒子。然而,NRRW队列无法获得来自内部发射器的剂量。25%的男性工人和17%的女性工人被确定为内部暴露监测对象。使用具有分层基线风险函数的分组生存数据的泊松回归方法来描述风险对累积外部辐射剂量的依赖性。该疾病按以下亚组进行分析:肺炎(1066例,包括17例流感)、COPD及其相关疾病(1517例)和其他剩余呼吸道疾病(479例) = .02)和其他呼吸道疾病死亡率的风险增加(ERR/Sv=2.30,95%CI:0.67,4.62;p = .01)随着累积外剂量的增加。辐射的影响在接受内部暴露监测的工人中更为突出。对于监测内部暴露的放射工作人员来说,每累积外部剂量COPD和相关疾病的死亡率风险降低具有统计学意义(ERR/Sv= -0.59,95%置信区间:-0.99,-0.05;p = .017),但在未受监测的工人中不显著(ERR/Sv= -0.43.95%CI:1.20,0.74;p = .42)。在受监测的放射工作人员中,观察到其他呼吸道疾病的风险在统计学上显著增加(ERR/Sv=2.46,95%置信区间:0.69,5.08;p = .019),但在未受监测的工人中没有(ERR/Sv=1.70,95%可信区间:-0.82,5.65;p = .结论:辐射暴露的影响可能因呼吸道疾病的类型而异。在肺炎中未发现任何效果;观察到COPD的死亡率风险降低以及其他呼吸道疾病的死亡率风险增加。需要更多的研究来验证这些发现。
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引用次数: 0
9th international symposium on physical, molecular, cellular, and medical aspects of Auger processes: preface. 关于俄歇过程的物理、分子、细胞和医学方面的第九届国际研讨会:序言。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2074755
Katherine A Vallis, Roger F Martin, Nadia Falzone
The 9th International Symposium on Physical, Molecular, Cellular, and Medical Aspects of Auger Processes took place from 22nd to 24th August 2019. This is a quadrennial event that has traditionally been held as a ‘satellite’ meeting of the International Congress for Radiation Research. Removal of an inner orbital electron through the photoelectric effect, electron capture, or internal conversion leads to a vacancy which is then filled by a cascade of electron transitions from the outer shells. These transitions are accompanied by the emission of low energy ‘Auger’ electrons or characteristic X-rays. Auger electrons have low energy (<25 keV), have a short track length and are densely ionizing. As a result, the absorbed radiation dose they deposit in biological material is extremely high but restricted to a nanoscale volume (a few nm) around the decay site. These qualities mean that Auger electron emitting radionuclides are suited to the ultra-precise delivery of radiation to individual cells, organelles or even to specific molecular targets, and so hold promise as oncologic therapeutic agents. The 9th Auger Symposium opened with a plenary presentation by Roger Howell, Rutgers University, who gave a comprehensive exposition of the advances in the use of Auger electrons in science and medicine during the period 2015–2019. The rest of the programme was organized into five scientific sessions focused on the availability and characteristics of ‘new’ Auger electron emitting radionuclides, physics, radiobiology, dosimetry and novel applications. Each session was headed by presentations by leaders in the field followed by selected papers from among submitted abstracts. Some of the research presented at the meeting has now been published as a collection of papers, together with a review article by Roger Howell summarizing his Keynote talk, in this ‘Special Auger Issue’ of the International Journal of Radiation Biology. The current series of Auger Symposia was inaugurated in 1987, when a group of radiation biologists and nuclear physicists met at the modest venue of the Oxfordshire village of Charney Bassett. It felt apt then that the 9th Symposium, which attracted 60 scientists from 13 countries, returned to Oxfordshire, although this time convening in the stunning Sultan Nazrin Shah Center located in the grounds of Worcester College, Oxford University. The scientific sessions were punctuated by opportunities for attendees to network and to enjoy some late summer sunshine and the tranquility of the College gardens and orchards. We would like to thank the other members of the organizing committee (Ana Denis-Bacelar, Bart Cornelissen, Samantha Terry and Akinari Yokoya) for their contributions, Anne-Marie Honeyman-Tafa for administrative assistance and Theragostics and the Gray Laboratory Cancer Research Trust for their sponsorship of the meeting. Auger electrons were independently identified by the physicists Lise Meitner and Pierre Auger; with Pierre Auger’
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引用次数: 0
Severity scoring systems for radiation-induced GI injury - prioritization for use of GI-ARS medical countermeasures. 辐射诱发胃肠道损伤的严重程度评分系统——GI- ars医疗对策使用的优先次序。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1080/09553002.2023.2210669
Doreswamy Kenchegowda, David L Bolduc, Lalitha Kurada, William F Blakely

Purpose: Severity scoring systems for ionizing radiation-induced gastrointestinal injury have been used in animal radiation models, human studies involving the use of radiation therapy, and human radiation accidents. Various radiation exposure scenarios (i.e. total body irradiation, total abdominal irradiation, etc.) have been used to investigate ionizing radiation-induced gastrointestinal injury. These radiation-induced gastrointestinal severity scoring systems are based on clinical signs and symptoms and gastrointestinal-specific biomarkers (i.e. citrulline, etc.). In addition, the time course for radiation-induced changes in blood citrulline levels were compared across various animal (i.e. mice, minipigs, Rhesus Macaque, etc.) and human model systems.

Conclusions: A worksheet tool was developed to prioritize individuals with severe life-threatening gastrointestinal acute radiation syndrome, based on the design of the Exposure and Symptom Tool addressing hematopoietic acute radiation syndrome, to rescue individuals from potential gastrointestinal acute radiation syndrome injury. This tool provides a triage diagnostic approach to assist first responders to assess individuals suspected of showing gastrointestinal acute radiation syndrome severity to guide medical management, hence enhancing medical readiness for managing radiological casualties.

目的:电离辐射引起的胃肠道损伤的严重程度评分系统已用于动物辐射模型、涉及使用放射治疗的人类研究和人类辐射事故。各种辐射暴露情景(如全身照射、腹部全照射等)已被用于研究电离辐射引起的胃肠道损伤。这些辐射引起的胃肠道严重程度评分系统是基于临床体征和症状以及胃肠道特异性生物标志物(如瓜氨酸等)。此外,在不同动物(如小鼠、小猪、恒河猴等)和人体模型系统中,比较了辐射引起的血瓜氨酸水平变化的时间过程。结论:基于针对造血急性辐射综合征的暴露与症状工具的设计,开发了一种工作表工具,可以对严重危及生命的胃肠道急性辐射综合征患者进行优先排序,以拯救潜在的胃肠道急性辐射综合征损伤患者。该工具提供了一种分诊诊断方法,帮助急救人员评估疑似表现出胃肠道急性辐射综合征严重程度的个人,以指导医疗管理,从而提高处理放射性伤亡的医疗准备。
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引用次数: 1
Transgenerational changes in Daphnia magna under radio frequency radiation in the juvenile and puberty period. 幼年期和发育期大水蚤在射频辐射下的跨代变化。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2087928
Elena I Sarapultseva, Darya V Uskalova, Ksenya V Ustenko, Viktor N Tikhonov, Igor A Ivanov, Alexander V Tikhonov

Purpose: To analyze the results of direct and transgenerational effects of radio frequency electromagnetic fields (RF-EMF) on the model organism of crustaceans Daphnia magna.

Materials and methods: D. magna were chronically exposed at 900 GHz EMF with an energy flux density (EFD) of about 1 mW/cm2 in the juvenile and pubertal periods of their ontogenesis. The cytotoxicity of exposure as well as survival, fertility and teratogenic effect of directly exposed daphnids and their progeny across three generations were analyzed.

Results and conclusions: The results of our study show that exposure of RF-EMF at juvenile period can significantly affect the fertility and size of irradiated daphnids and their offspring of the first generation. The decrease in fertility may be associated with a cytotoxic effect on the cells of irradiated animals. The reduction in the size of the terminal spine and the body of individuals is an indicator of the negative impact of radiation on the protective strategy of the crustacean population. The reproductive process is restored by the second generation. The results of our study provide further insights into the possible mechanisms underlying the in vivo effects of RF-EMF.

目的:分析射频电磁场(RF-EMF)对模式生物大水蚤(Daphnia magna)的直接和跨代影响。材料和方法:在发育的幼年期和发育期,长期暴露在900 GHz电磁场下,能量通量密度(EFD)约为1 mW/cm2。分析了直接暴露的水蚤及其后代三代的细胞毒性、存活率、生育力和致畸效应。结果与结论:本研究结果表明,幼年期接触射频电磁场对受辐射水蚤及其第一代后代的生育能力和体型有显著影响。生育能力的下降可能与受辐照动物细胞的细胞毒性作用有关。个体末端脊椎和身体尺寸的减小是辐射对甲壳类种群保护策略产生负面影响的一个指标。繁殖过程由第二代恢复。我们的研究结果为射频电磁场体内效应的可能机制提供了进一步的见解。
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引用次数: 0
Effects of gamma irradiation on morphology and protein differential in M1V1 population of Vanilla planifolia Andrews. γ辐照对planifolia Andrews M1V1群体形态和蛋白质差异的影响。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2087932
Rohayu Ma'Arup, Nur Syazwani Ali, Fisal Ahmad, Zaiton Ahmad, Mohamad Feisal Mohamed Norawi, Homaa Faezah Moinuddin

Purpose: Lower doses (1-10 Krad) of gamma-rays (γ) are frequently used in obtaining useful mutants in diverse plant species, whereas no report on gamma (γ) irradiation being used to develop new varieties of vanilla from vanilla cuttings. This study assessed the potential of lower doses of gamma-rays for vanilla mutation breeding.

Materials and methods: We compared the morphological differences between vanilla plants irradiated at different lower doses of gamma radiation (10, 30, 40, and 50 Gy). We quantified protein and compared variation from the extracted protein of vanilla shoots regenerated between treatments.

Results and conclusions: After 44 weeks, the results showed that the growth of M1V1 (mutation 1 in vegetative cycle 1) plants at 0 Gy (control) is highest compared with other doses of gamma radiation in terms of plant height and the number of shoots. However, the highest measurement for root length is at 10 Gy. The slowest growth rate was obtained from 40 to 50 Gy. Based on the unique band of protein that appears on the SDS-PAGE gel, 10 Gy has three unique bands at loci 0.105 RF, two bands lie at loci between 0.164 RF and 0.234 RF. While 30 Gy is absent two unique bands at loci 0.234 RF compared to 0 Gy. Thus, the dose of gamma rays at 10 Gy gave the highest number of protein fragments, which detected polymorphisms between the control (0 Gy) and the plants treated. To our knowledge, this is the first report of the protein variation in M1V1 of irradiated vanilla plants.

目的:低剂量(1-10克拉)的γ射线(γ)经常用于在不同的植物物种中获得有用的突变体,而伽马(γ)照射用于从香草插枝中开发香草新品种尚无报道。本研究评估了低剂量伽马射线对香草突变育种的潜力。材料和方法:我们比较了不同低剂量γ辐射(10、30、40和50 Gy)照射下香草植株的形态差异。我们量化了蛋白质,并比较了不同处理间再生香草芽提取蛋白质的差异。结果与结论:44周后,0 Gy(对照)处理下M1V1(营养循环1突变1)植株的株高和芽数均高于其他剂量的γ辐射处理。然而,根长度的最高测量值是在10 Gy。生长速率在40 ~ 50 Gy范围内最慢。根据SDS-PAGE凝胶上出现的蛋白独特条带,10 Gy在0.105 RF位点有3条独特条带,在0.164 RF至0.234 RF位点有2条独特条带。而与0 Gy相比,30 Gy在0.234 RF位点缺少两个独特的波段。因此,剂量为10 Gy的伽马射线产生了最多的蛋白质片段,检测到对照(0 Gy)和处理植株之间的多态性。据我们所知,这是第一个关于辐照香草植株M1V1蛋白变异的报道。
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引用次数: 0
Genomic DNA damage induced by co-exposure to DNA damaging agents and pulsed magnetic field. DNA损伤剂与脉冲磁场共同暴露诱导的基因组DNA损伤。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2121873
Beatriz López-Díaz, Silvia Mercado-Sáenz, Antonio M Burgos-Molina, Alejandro González-Vidal, Francisco Sendra-Portero, Miguel J Ruiz-Gómez

Purpose: Many articles describe the effects of extremely low-frequency magnetic fields (MFs) on DNA damage induction. However, the mechanism of MF interaction with living matter is not yet known with certainty. Some works suggest that MF could induce an increase in the efficacy of reactive oxygen species (ROS) production. This work investigates whether pulsed MF exposure produces alterations in genomic DNA damage induced by co-exposure to DNA damaging agents (bleomycin and methyl methanesulfonate (MMS)).

Materials and methods: Genomic DNA, prepared from S. cerevisiae cultures, was exposed to pulsed MF (1.5 mT peak, 25 Hz) and MMS (0-1%) (15-60 min), and to MF and bleomycin (0-0.6 IU/mL) (24-72 h). The damage induced to DNA was evaluated by electrophoresis and image analysis.

Results: Pulsed MF induced an increment in the level of DNA damage produced by MMS and bleomycin in all groups at the exposure conditions assayed.

Conclusions: Pulsed MF could modulate the cytotoxic action of MMS and bleomycin. The observed effect could be the result of a multifactorial process influenced by the type of agent that damages DNA, the dose, and the duration of the exposure to the pulsed MF.

目的:许多文章描述了极低频磁场(MFs)对DNA损伤诱导的影响。然而,MF与生物物质相互作用的机制尚不明确。一些研究表明,MF可以诱导活性氧(ROS)产生的功效增加。这项工作调查了脉冲MF暴露是否会产生DNA损伤剂(博来霉素和甲磺酸甲酯)共同暴露引起的基因组DNA损伤的改变。材料和方法:从酿酒酵母培养物中制备基因组DNA,将其暴露于脉冲MF (1.5 mT峰,25 Hz)和MMS (0-1%) (15-60 min),以及MF和博来霉素(0-0.6 IU/mL) (24-72 h)中。通过电泳和图像分析评估对DNA的损伤程度。结果:在暴露条件下,脉冲MF诱导各组MMS和博来霉素产生的DNA损伤水平增加。结论:脉冲MF可调节MMS和博来霉素的细胞毒作用。观察到的效果可能是一个多因素过程的结果,受破坏DNA的药剂类型、剂量和暴露于脉冲MF的持续时间的影响。
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引用次数: 1
Candidate biomarkers and persistent transcriptional responses after low and high dose ionizing radiation at high dose rate. 高剂量率低剂量和高剂量电离辐射后的候选生物标志物和持续转录反应。
IF 2.1 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 Epub Date: 2023-08-07 DOI: 10.1080/09553002.2023.2241897
Zhenqiu Liu, John Cologne, Sally A Amundson, Asao Noda

Purpose: Development of an integrated time and dose model to explore the dynamics of gene expression alterations and identify biomarkers for biodosimetry following low- and high-dose irradiations at high dose rate.

Material and methods: We utilized multiple transcriptome datasets (GSE8917, GSE43151, and GSE23515) from Gene Expression Omnibus (GEO) for identifying candidate biological dosimeters. A linear mixed-effects model with random intercept was used to explore the dose-time dynamics of transcriptional responses and to functionally characterize the time- and dose-dependent changes in gene expression.

Results: We identified genes that are correlated with dose and time and discovered two clusters of genes that are either positively or negatively correlated with both dose and time based on the parameters of the model. Genes in these two clusters may have persistent transcriptional alterations. Twelve potential transcriptional markers for dosimetry-ARHGEF3, BAX, BBC3, CCDC109B, DCP1B, DDB2, F11R, GADD45A, GSS, PLK3, TNFRSF10B, and XPC were identified. Of these genes, BAX, GSS, and TNFRSF10B are positively associated with both dose and time course, have a persistent transcriptional response, and might be better biological dosimeters.

Conclusions: With the proposed approach, we may identify candidate biomarkers that change monotonically in relation to dose, have a persistent transcriptional response, and are reliable over a wide dose range.

目的:建立一个综合时间和剂量模型,以探索高剂量率低剂量和高剂量照射后基因表达改变的动态,并确定生物剂量学的生物标志物。材料和方法:我们利用Gene Expression Omnibus (GEO)的多个转录组数据集(GSE8917、GSE43151和GSE23515)鉴定候选生物剂量计。采用随机截距的线性混合效应模型来探索转录反应的剂量-时间动力学,并从功能上表征基因表达的时间和剂量依赖性变化。结果:我们发现了与剂量和时间相关的基因,并根据模型参数发现了两组与剂量和时间均呈正相关或负相关的基因。这两个基因簇中的基因可能有持续的转录改变。鉴定出12个潜在的剂量学转录标记——arhgef3、BAX、BBC3、CCDC109B、DCP1B、DDB2、F11R、GADD45A、GSS、PLK3、TNFRSF10B和XPC。在这些基因中,BAX、GSS和TNFRSF10B与剂量和时间过程呈正相关,具有持续的转录反应,可能是更好的生物剂量计。结论:通过提出的方法,我们可以确定候选生物标志物,这些生物标志物随剂量单调变化,具有持续的转录反应,并且在大剂量范围内是可靠的。
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引用次数: 0
Correction. 更正。
IF 2.1 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 Epub Date: 2022-11-14 DOI: 10.1080/09553002.2022.2147347
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引用次数: 0
The delayed effects of acute radiation exposure (DEARE): characteristics, mechanisms, animal models, and promising medical countermeasures. 急性辐照的延迟效应(DEARE):特征、机制、动物模型和有前途的医疗对策。
IF 2.1 4区 医学 Q2 BIOLOGY Pub Date : 2023-01-01 Epub Date: 2023-03-16 DOI: 10.1080/09553002.2023.2187479
Tong Wu, Christie M Orschell

Purpose: Terrorist use of nuclear weapons and radiation accidents put the human population at risk for exposure to life-threatening levels of radiation. Victims of lethal radiation exposure face potentially lethal acute injury, while survivors of the acute phase are plagued with chronic debilitating multi-organ injuries for years after exposure. Developing effective medical countermeasures (MCM) for the treatment of radiation exposure is an urgent need that relies heavily on studies conducted in reliable and well-characterized animal models according to the FDA Animal Rule. Although relevant animal models have been developed in several species and four MCM for treatment of the acute radiation syndrome are now FDA-approved, animal models for the delayed effects of acute radiation exposure (DEARE) have only recently been developed, and there are no licensed MCM for DEARE. Herein, we provide a review of the DEARE including key characteristics of the DEARE gleaned from human data as well as animal, mechanisms common to multi-organ DEARE, small and large animal models used to study the DEARE, and promising new or repurposed MCM under development for alleviation of the DEARE.

Conclusions: Intensification of research efforts and support focused on better understanding of mechanisms and natural history of DEARE are urgently needed. Such knowledge provides the necessary first steps toward the design and development of MCM that effectively alleviate the life-debilitating consequences of the DEARE for the benefit of humankind worldwide.

目的:恐怖分子使用核武器和辐射事故使人类面临暴露于危及生命的辐射水平的风险。致命辐照的受害者可能会面临致命的急性损伤,而急性期的幸存者则会在辐照后数年内受到多器官慢性损伤的困扰。开发治疗辐照的有效医疗对策(MCM)是一项迫切需求,这在很大程度上依赖于根据美国食品及药物管理局动物规则在可靠且特征明确的动物模型中进行的研究。虽然已在多个物种中开发出相关的动物模型,而且目前已有四种治疗急性辐射综合征的 MCM 获得 FDA 批准,但治疗急性辐照延迟效应(DEARE)的动物模型最近才开发出来,而且目前还没有获得许可的治疗 DEARE 的 MCM。在此,我们将对辐照延迟效应进行综述,包括从人类和动物数据中收集的辐照延迟效应的主要特征、多器官辐照延迟效应的共同机制、用于研究辐照延迟效应的小型和大型动物模型,以及正在开发的用于缓解辐照延迟效应的新型或再利用型中药:结论:亟需加强研究并提供支持,以更好地了解 DEARE 的机制和自然史。这些知识为设计和开发可有效缓解 DEARE 对生命造成危害的中药迈出了必要的第一步,从而造福于全人类。
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引用次数: 0
Protective effect of acrocarpus fraxinifolius extract against hepatic fibrosis induced by Gamma irradiation and carbon tetrachloride in albino rats. 芦竹提取物对γ辐射和四氯化碳诱导的白化大鼠肝纤维化的保护作用。
IF 2.6 4区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2087926
Omama E El-Shawi, Heba A S El-Nashar, Sahar S Abd El-Rahman, Omayma A Eldahshan, Abdel Nasser B Singab

Purpose: Liver fibrosis is considered as one of the ultimate outcomes of chronic liver disorders, characterized by outrageous cell proliferation and abnormal deposition of extracellular matrix, resulting in sever pathological distortions in the architecture and performance of liver tissues. The present study aimed to investigate the protective properties of aqueous methanol extract of Acrocarpus fraxinifolius leaves (AFL) against liver fibrosis induced by dual toxicity of γ-irradiation and carbon tetrachloride (CCl4) in rats.

Methods: The animals were exposed to 2 Gy irradiation once/week concurrently with intraperitoneal administration of CCl4 (0.2 mL/100 g body weight) for seven weeks. Afterwards, liver toxicity and fibrosis were assessed biochemically at cellular and molecular as well as histopathological levels.

Results: The livers of intoxicated rats showed distinct structural and functional changes, compared with the normal rats. The administration of AFL (500 mg/kg, p.o) significantly ameliorated the histopathological manifestations of fibrotic liver evidenced by mitigated steatosis progression, necrosis, fibrotic septa, apoptotic bodies, and immunochistochemical studies of alpha-smooth muscle actin. Also, AFL increased the final body weight, total protein, albumin levels and albumin/globulin ratio. While, the absolute liver weight, liver enzymes, total cholesterol and triglycerides were reduced. A significant modulation was observed in hydroxyproline, transforming growth factor-β and collagen-1expression. Furthermore, AFL exerted a direct effect on liver fibrosis by promoting extracellular matrix degradation via overexpression of the tissue inhibitor metalloproteinase-1, coupled with decease of metalloproteinase-9 activity.

Conclusions: Our findings suggested that AFL effectively improved the architecture of fibrotic liver and modified the biochemical markers of liver fibrosis.

目的:肝纤维化被认为是慢性肝脏疾病的最终结局之一,其特征是细胞增生严重,细胞外基质异常沉积,导致肝组织结构和功能的严重病理扭曲。本研究旨在探讨芦竹叶甲醇水提物(AFL)对γ-辐射和四氯化碳(CCl4)双重毒性所致大鼠肝纤维化的保护作用。方法:小鼠接受2 Gy辐射,每周1次,同时腹腔注射CCl4 (0.2 mL/100 g体重),连续7周。然后,在细胞、分子和组织病理水平上进行肝毒性和纤维化的生化评估。结果:与正常大鼠相比,中毒大鼠肝脏有明显的结构和功能变化。AFL (500 mg/kg, p.o)可显著改善纤维化肝的组织病理学表现,包括减轻脂肪变性进展、坏死、纤维化间隔、凋亡小体和α -平滑肌肌动蛋白的免疫组织化学研究。此外,AFL还增加了末重、总蛋白、白蛋白水平和白蛋白/球蛋白比。肝脏绝对重量、肝酶、总胆固醇和甘油三酯均降低。羟脯氨酸、转化生长因子-β和胶原-1的表达显著调节。此外,AFL通过过度表达组织抑制剂金属蛋白酶-1,同时降低金属蛋白酶-9活性,促进细胞外基质降解,从而对肝纤维化产生直接影响。结论:AFL能有效改善肝纤维化的结构,改变肝纤维化的生化指标。
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引用次数: 11
期刊
International Journal of Radiation Biology
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