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SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.
La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.
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Animals , Female , Rats , Drugs, Chinese Herbal , Protective Agents/administration & dosage , Heavy Ions/adverse effects , Scutellaria baicalensis/chemistry , Brain/drug effects , Brain/radiation effects , Corticotropin-Releasing Hormone , Enzyme-Linked Immunosorbent Assay , Rats, Wistar , Apoptosis/drug effects , Apoptosis/radiation effects , Adrenocorticotropic Hormone , Proliferating Cell Nuclear Antigen , Endocrine System/drug effects , Endocrine System/radiation effects , Immunologic Factors/antagonists & inhibitors , Kidney/drug effects , Kidney/radiation effectsABSTRACT
AIM: To investigate the changes of protein expressions in human lens epithelial cells(SRA01/04)undergoing oxidative damage, hoping to provide new protein target for the pathogenesis of age-related cataract(ARC).METHODS: SRA01/04 cells were divided into experimental group and control group. In the experimental group, cells were irradiated with ultraviolet-B(UVB)for 10min to establish the model of oxidative damage, whereas cells in the control group were untreated. Protein expression profile from the two groups was sequenced by isobaric tags for relative and absolute quantitation(iTRAQ). The filtering criteria that fold change >1.2 and p<0.05 was used to determine the differentially expressed proteins(DEPs). Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were utilized for functional enrichment analysis of the top 50 DEPs with either up-regulated or down-regulated significance. Furthermore, Pathway commons software was used to establish the protein-protein interaction(PPI)network.RESULTS: Overall, 552 DEPs were screened out. A total of 176 DEPs were up-regulated in the experimental group compared with the control group, including HMGB1 and USP1, while 376 DEPs were down-regulated, including POLR2A and POLR2B. GO and KEGG enrichment analysis indicated that the top 50 DEPs with up-regulated or down-regulated significance were involved in various crucial biological processes and signaling pathways. PPI network revealed that oxidative damage repair(ODR)-related proteins might play a key role in UVB-induced oxidative damage.CONCLUSIONS: The expressions of multiple proteins, especially ODR-related proteins, can be altered in SRA01/04 cells via UVB irradiation. These findings may provide cellular-related insights into the pathogenesis of ARC and into proteins or pathways associated with therapeutic targets.
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Non-invasive control of the drug molecules accessibility is a key issue in improving diagnostic and therapeutic procedures. Some studies have explored the spatiotemporal control by light as a peripheral stimulus. Phototriggered drug delivery systems (PTDDSs) have received interest in the past decade among biological researchers due to their capability the control drug release. To this end, a wide range of phototrigger molecular structures participated in the DDSs to serve additional efficiency and a high-conversion release of active fragments under light irradiation. Up to now, several categories of PTDDSs have been extended to upgrade the performance of controlled delivery of therapeutic agents based on well-known phototrigger molecular structures like o-nitrobenzyl, coumarinyl, anthracenyl, quinolinyl, o-hydroxycinnamate and hydroxyphenacyl, where either of one endows an exclusive feature and distinct mechanistic approach. This review conveys the design, photochemical properties and essential mechanism of the most important phototriggered structures for the release of single and dual (similar or different) active molecules that have the ability to quickly reason of the large variety of dynamic biological phenomena for biomedical applications like photo-regulated drug release, synergistic outcomes, real-time monitoring, and biocompatibility potential.
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Abstract Objective This study aimed to analyze the effect of irradiation on the push-out bond strength of mineral trioxide aggregate (MTA) and Biodentine to radicular dentin. Methodology A total of 60 extracted mature human teeth with single root canals were categorized into two groups (irradiated and non-irradiated) (n=30). Each group was further divided into two sub-groups based on cements used (Biodentine and MTA). Then, a cumulative radiation dose of 60 Gy was divided into 30 fractions (two Gy for every fraction) and administered for five successive days per week over six weeks. Obturation was then performed using MTA and Biodentine. Afterwards, 1.5 mm thick horizontal sections were procured from the middle one-third of all the specimens and then subjected to push-out bond test. Results were analyzed using one-way analysis of variance with post-hoc Tukey's test. Results The bond strength of Biodentine and MTA to irradiated teeth was lower than non-irradiated teeth. Highest push-out bond strength was observed in non-irradiated specimens filled with Biodentine (p=0), followed by irradiated specimens filled with Biodentine (p=0); non-irradiated specimens filled with MTA (p=0); and irradiated specimens filled with MTA (p=0.9). Conclusion The push-out bond strength of Biodentine and MTA to root canal dentin decreased significantly post irradiation.
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@#Breast cancer is the most common malignancy and the fifth leading cause of cancer-related mortality in the world. Breast cancer is a global health problem that poses a heavy burden on patients and their families as well as socioeconomic development. As an important component in the management of breast cancer, radiotherapy plays a vital role in its comprehensive treatment. This review describes advances made toward the application of adjuvant radiotherapy in the treatment of breast cancer.
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Objective To analyze the occupational hazards and protective measures for personnel in an iodine-125(125I) seed source production company. Methods In 2022, a 125I seed source production enterprise in Guangdong Province was selected as the research subject. The occupational hazards in the workplace of the research subject was identified using the system engineering analysis method. The FLUAK program based on Monte Carlo method was used to simulate the blocking protection of the production of the 125I seed source, and to estimate the dose of internal and external irradiation of seed source that affected workers. Results The main occupational radiation hazards in the seed production were non-sealed radioactive materials, including external irradiation from X-ray and γ ray and internal irradiation from aerosols formed by iodine volatilization. Estimated maximum dose equivalent rate around the chest and eye lens for workers were 0.52 and 0.02 μSv/h, respectively. The expected annual effective dose for workers in each work site was 0.035 mSv, and the expected annual equivalent dose to the eye lens for all workers in various work sites was 0.001 mSv. The maximum annual equivalent dose of operator's hand was 80.620 mSv. The maximum dose of internal irradiation to the worker was 18.750 mSv, which was caused by the volatilization of nuclides. Conclusion With effective protection measures for internal and external irradiation in place, the annual exposure doses for seed production personnel and operator’s hand are below the national limits. Adequate measures should be taken on hand protection.
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Objective The radioactivity level in historical waste from a plant is high, and decommissioning operators may be exposed to high radiation doses. The objective of the study is to carry out a radiation safety analysis of the retrieval and conditioning of naturally occurring radioactive material (NORM) waste, put forward appropriate radiation protection measures, and minimize the exposure doses of operators. Methods The source terms of NORM waste in the temporary storehouse were analyzed; MicroShield, a point kernel integration program, was used for modeling and calculation; and radiation protection measures under decommissioning conditions were put forward based on on-site monitoring data. Results The maximum gamma dose rate calculated near the waste pile in the temporary storehouse was 313.9 μGy/h, equivalent to the monitoring level; distance decay and appropriate shielding measures significantly reduced gamma dose rates for operators. Conclusion Decommissioning sites of temporary storehouses are of great harm to operators. Measures such as shielding, isolation, remote operations, and personal protection can effectively reduce the exposure doses of operators.
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The application of immune checkpoint inhibitors (ICI) has rewritten the current treatment pattern of non-small cell lung cancer. However, single-agent ICI has disadvantages such as small benefit population and slow tumor cytoreduction effect. Therefore, various immunizations combined with other treatment methods are becoming clinical hotspots. Low-dose irradiation shows a significant anti-tumor synergistic effect through activating the body's immune system, and its potential for adjuvant immunotherapy has transformed traditional radiotherapy from local radical treatment to immune adjuvant. This article reviews the current research progress of ICI combined with low-dose irradiation in the treatment of non-small cell lung cancer.
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Objective:To analyze whether involved-field irradiation (IFI) was associated with improved survival and reduced treatment-related adverse events compared with elective nodal irradiation (ENI) in Chinese patients with esophageal squamous cell carcinoma receiving radiotherapy.Methods:Literature review was conducted from CNKI, Wanfang Data, PubMed, Embase, Web of Science and Cochrane Central databases (until July 31, 2022). Relevant data were collected according to the inclusion and exclusion criteria. Primary outcomes included overall survival (OS) rate and treatment-related adverse events. Secondary outcomes included progression-free survival (PFS) rate and local control rate (LCR). Risk of bias was assessed using the Cochrane Risk of Bias tool. The quality of the results was assessed by using the meta analysis of Evidence Evaluation and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods.Results:A total of 7 articles with 918 patients were included of which 465 received IFI and 453 received ENI. The 1-, 2-, 3-and 5-year OS rates in the IFI group were not significantly different from those in the ENI group (1-year OS rate: RR=1.00, 95% CI=0.94-1.07, P=0.97, high certainty; 2-year OS rate: RR=1.01, 95% CI=0.90-1.13, P=0.90, high certainty; 3-year OS rate: RR=0.86, 95% CI=0.71-1.05, P=0.14, high certainty; 5-year OS rate: RR=0.76, 95% CI=0.42-1.37, P=0.36, low certainty). In the IFI group, patients with ≥grade 2 acute radiation esophagitis ( RR=0.71, 95% CI=0.58-0.87, P=0.001, high certainty), ≥grade 3 acute radiation esophagitis ( RR=0.39, 95% CI=0.24-0.64, P<0.001, high certainty) and ≥grade 2 acute radiation pneumonitis ( RR=0.72, 95% CI=0.52-0.99, P=0.04, high certainty) were significantly lower compared with those in the ENI group. However, no significant differences were observed in the incidence of ≥grade 3 late radiation esophagitis, ≥grade 3 acute radiation pneumonitis and ≥grade 3 late radiation pneumonitis between two groups. No significant differences were noted in the 1-, 2-, 3-PFS rates and LCR between two groups. Conclusions:For Chinese patients with esophageal squamous cell carcinoma, IFI and ENI yield similar efficacy in terms of OS, PFS and LCR. However, IFI has a lower incidence of ≥grade 2 acute radiation esophagitis, ≥grade 3 acute radiation esophagitis and ≥grade 2 acute radiation pneumonitis than ENI.
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Objective:To analyze the prognosis and risk factors for brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete resection, aiming to identify those most likely to benefit from prophylactic cranial irradiation (PCI).Methods:Clinical data of 94 patients with LS-SCLC treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2005 to December 2018 who underwent complete resection were retrospectively analyzed, including 31 cases treated with PCI and 63 without PCI. Prognostic factors and risk factors of BM were analyzed by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. Independent risk factors of overall survival (OS) and BM were assessed by multivariate Cox regression model.Results:The 2-year and 5-year OS rates were 80.6% and 61.3% in the PCI group, and 61.9% and 46.0% in the non-PCI group, respectively ( P=0.001). The 2-year and 5-year brain metastasis-free survival (BMFS) rates were 80.6% and 54.8% in the PCI group, and 57.1% and 42.9% in the non-PCI group, respectively ( P=0.045). The 2-year and 5-year progression-free survival (PFS) rates were 71.0% and 48.4% in the PCI group, and 49.2% and 34.9% in the non-PCI group, respectively ( P=0.016). PCI could improve OS in patients with pII/III stage LS-SCLC ( P=0.039, P=0.013), but the OS benefit in patients with pI stage LS-SCLC was not significant ( P=0.167). BM occurred in 3 patients (9.7%) in the PCI group, which was significantly lower than that in the non-PCI group ( n=17, 27.0%; P=0.044); there was no significant difference in the BM rate of patients with pI and pII stage LS-SCLC between PCI and non-PCI groups ( P=0.285, P=0.468); and the BM rate of patients with pIII stage LS-SCLC in the PCI group was significantly lower than that in the non-PCI group ( P=0.041). Multivariate analysis showed age ≥60 ( HR=2.803, P=0.001), BM ( HR=2.239, P=0.022), no PCI ( HR=0.341, P=0.004) and pathological stage pII/III ( HR=4.963, P=0.002) were the independent high-risk factors affecting OS; and pathological stage pII/III ( HR=11.665, P=0.007) was an independent high-risk factor affecting BM. Conclusions:LS-SCLC patients with pII-III stage have a higher risk of developing BM and poor prognosis after complete resection, and should receive PCI treatment. However, LS-SCLC patients with pI stage may not benefit significantly.
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Objective:To evaluate the effects of whole brain irradiation (WBI) and fecal microbiota transplantation (FMT) on hippocampal neurogenesis and the composition of gut microbiota in mice.Methods:Forty specific pathogen free ICR male mice (8-week-old, weighed 30 g) were divided into four groups by simple random sample method: control group (group C), radiation group (group R), group C+FMT and group R+FMT, 10 in each group. Animal models were established by WBI at a dose of 10 Gy by 4 MeV electron beam. In group C+FMT and group R+FMT, mice were gavaged with normal fecal bacteria suspension on day 2 post-irradiation, while those in group C and group R were gavaged with phosphate buffered saline as alternative. Hippocampal tissues and feces in four groups were collected on day 15 post-irradiation. 16S rRNA sequencing was used to detect the species and abundance of fecal flora. BrdU +/NeuN + immunofluorescence staining was performed to observe the neurogenesis in hippocampus of mice. Results:WBI and FMT had no effect on survival rate and body weight of mice. WBI induced the inhibition of hippocampal neurogenesis and flora disorder. The quantity of Bacteroideae and Rumen bacteria was increased by 28.6% and 102.9%, whereas that of Lactobacillus was significantly decreased by 70.6% ( P<0.05). FMT regulated the abundance of bacteria. The abundance of Enterobacteriaceae was significantly declined by 65.1% ( P=0.028), while that of Lactobacillus was increased by 58.2% ( P=0.015). FMT also promoted hippocampal neurogenesis to some extent after WBI. Conclusions:This preliminary study demonstrates that FMT alleviates the inhibition of hippocampal neurogenesis and flora disorder induced by WBI in mice. Ionizing radiation directly acting on the whole brain of mice indirectly disturbs the composition of gut microbiota, which in turn affects the degree of hippocampal neurogenesis in the brain of mice. There is a bidirectional interaction between gut microbiota and brain.
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Objective:To investigate the role of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) by meta-analysis.Methods:Studies published from January 1, 1980 to August 30, 2021 were searched systematically in PubMed, Embase, Cochrane Systematic Review database and China National Knowledge Infrastructure Database. The searching keywords included "non-small cell lung cancer", "randomized controlled trial", "prophylactic cranial irradiation" and "clinical trial". The data extracted from the above studies were analyzed using Review Manager 5.3 and Stata 12.0 software. Outcomes included the development of brain metastases (BM), overall survival (OS), disease-free survival (DFS), toxicity, and quality of life (QoL).Results:Ten trials, including 2005 NSCLC patients, met the inclusion criteria. Patients who underwent PCI had a significantly lower risk of BM than those who did not ( OR=0.29, 95% CI: 0.22-0.40, P<0.001). Compared with non-PCI group, DFS in PCI group was significantly increased ( HR=0.75, 95% CI: 0.63-0.89, P=0.001). However, there was no significant difference in OS ( OR=0.90, 95% CI: 0.69-1.18, P=0.45). In addition, the incidence of fatigue was significantly increased in the PCI group ( OR=2.64, 95% CI: 1.58-4.40, P<0.001). There was no significant difference in cognitive impairment between the PCI and non-PCI groups ( OR=3.60, 95% CI: 0.97-13.32, P=0.06). Conclusions:PCI is the standard treatment for NSCLC. Compared with non-PCI, PCI significantly reduces the incidence of BM and prolongs the DFS of NSCLC patients. The effect of PCI-related toxicity on the QoL and long-term OS needs further study.
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Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.
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Objective:To investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.Methods:C57BL/6 mice were randomly divided into control group, racanisodamine group, 18 Gy irradiation group (model group) and racanisodamine combined with 18 Gy irradiation group (treatment group), with 5 mice in each group. The mice in the treatment group received racanisodamine (5 mg/kg) intraperitoneally 3 d before irradiation and contained the whole experiments. Then, single chest irradiation of 18 Gy X-rays was performed both in the model and treatment groups. The racanisodamine group and treatment group received racanisodamine intraperitoneally once a day until 6 weeks after irradiation. The mice were killed at 6 weeks after irradiation. The lung histopathology was observed by HE staining. Serum and bronchial alveolar lavage fluid (BALF) inflammatory cytokines such as TNF-α, IL-1β and IL-6 were determined by ELISA method. Cell senescence was detected by SA-β-Gal staining. The expressions of Nrf2, p-Nrf2 and p62 in lung tissue were performed by immunehistochemistry and Western blot assays.Results:Compared with the model group, the scores of HE staining were decreased ( t=8.66, P<0.01), the number of infiltrated inflammatory cells in BALF were decreased ( t=10.70, P<0.01), and protein concentration in BALF had lower levels ( t=6.75, P<0.01), the serum TNF-α, IL-1β and IL-6 were decreased significantly ( t=8.17, 4.58, 6.54, P<0.01), the activity of SA-β-gal was decreased, and the expressions of Nrf2, p-Nrf2 were enhanced ( t=6.42, 7.30, P<0.01), while the expression of p62 was reduced ( t=4.62, P<0.01) in the treatment group. Conclusions:Racanisodamine plays the protective effect of radiation-induced lung injury by alleviating inflammation associating with the activating of Nrf2-related pathway, which reversed radiation-induced cell senescence.
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Objective:To explore the present state of radiation protection in an operational large-sized irradiation facility and the distribution of incurred radiation doses in the controlled area under abnormal conditions, and to analyze the acompanied radiation risk.Methods:With an irradiation facility in operation as the research object, the radiation doses were measured using AT1121 X and gamma dose rate meters for the soruce both in working and storage. Thermoluminescent dosimeters (TLDs) were used to measure the dose distribution in an irradiation field under abnormal conditions. The radiation safety features were checked against the several relevant national standards, with the radiation risks evaluated.Results:The radiation dose rates were in the range of 0.09-0.11 μSv/h, lower than the environmental background level whether in storage or working. Under abnormal working conditions, the radiation dose values from high to low were 1.0-101.3 Sv, 32.7-514.0 mSv and 8.7-183.2 μSv in the irradiation field, respectively. At the outside maze, the doses were close to the background level.Conclusions:The protection features of the irradiation facility meet the requirements of the relevant national standards. Under abnormal conditions, radiation could cause serious damages to the persons staying in the irradiation field. These persons were suggested to access to maze as soon as possible to reduce the exposure time, and activate the emergency protection equipments to deescalate the 60Co source onto the well.
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Objective:To study the effects of FLASH irradiation (FLASH-RT) and conventional irradiation (CONV-RT) on gene expression profile in mouse liver, in order to provide theoretical basis of the potential mechanism of FLASH-RT.Methods:A total of 11 C57BL/6J male mice were divided into healthy control group (Ctrl group), CONV-RT group and FLASH-RT group according to random number table method. Mouse abdomen was treated with 12 Gy CONV-RT or FLASH-RT. Then the mice were killed by neck removal, and the liver tissues were collected to extract total RNA for transcriptome sequencing (RNA-Seq) that was then analyzed by bio-informatics analysis to investigate the changes of gene expression profiles. The mRNA expression levels of Stat1, Irf9 and Rela were verified by quantitative real-time PCR assay.Results:1 762 differentially expressed genes (DEGs) were identified in group FLASH-RT vs. CONV-RT. Among them, 660 genes were up-regulated and 1 102 genes were down-regulated. 1 918 DEGs were identified in groups FLASH-RT vs. Ctrl. Among them, 728 genes were up-regulated and 1 190 genes were down-regulated. 1 569 DEGs were identified in group CONV-RT vs. Ctrl. Among them, 1 046 genes were up-regulated and 523 genes were down-regulated. According to Gene Ontology (GO) analysis, these DEGs from groups FLASH-RT vs. CONV-RT were involved in various functions including defense response to virus, other organisms in cell components, adenylyltransferase activity in molecular function activity. These DEGs from group FLASH-RT vs. Ctrl were involved in various functions including defense response to other oranisms, endoplasmic reticulum chaperone complex, double-stranded RNA binding and so on. These DEGs from group FLASH-RT vs. CONV-RT were involved in several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including influenza A, Herpes simplex infection and so on. These DEGs from group FLASH-RT vs. Ctrl were involved in several KEGG pathways including influenza A, NOD-like receptor signaling pathway. Stat1 was likely to be activated by FLASH radiation. The quantitative real-time PCR assay showed that FLASH-RT obviously increased the mRNA expressions of Stat1, Irf9 and Rela ( t=6.62, 2.11, 1.67, P<0.05). Conclusions:FLASH-RT and CONV-RT could alter gene expression profiles in mouse liver tissues, and these DEGs are involved in multiple radiobiological functional pathways. In comparison with CONV-RT, FLASH-RT induces a low level of liver injury, which may due to hypoxia radiation resistance.
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Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.
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Objetivo: Describir las aberraciones citogenéticas que pueden ser observadas por medio de la técnica Giemsa en fluorescencia y encontradas en pacientes con cáncer antes y después de ser sometidos a tratamiento con radioterapia. Métodos: Se analizó un mínimo de 200 metafases en primera división mitótica antes y después del tratamiento de radioterapia en nueve pacientes que asistieron a la sección de radioterapia del Hospital San Juan de Dios Costa Rica. En cada caso se contabilizó cada tipo de cromosomopatía por medio de la prueba de Giemsa en fluorescencia y utilizando bromodeoxiuridina y naranja de acridina. Resultados: Las cromosomopatías producidas por radioterapia se observaron tanto antes como después del tratamiento sin embargo destacó el incremento en la frecuencia de los cromosomas dicéntricos y anillos céntricos una vez finalizada la terapia. La frecuencia de fracturas cromatídicas de asociaciones satelíticas y de alteraciones morfológicas no se ve afectada por la radioterapia. Uno de los participantes presentó un recuento mitótico bajo. Conclusión: La radioterapia aumenta significativamente la frecuencia de los cromosomas dicéntricos y dicéntricos más anillos en la muestra en estudio. Este trabajo es relevante por ser el primer estudio en Costa Rica en el que se analizan los cromosomas dicéntricos como biomarcadores de exposición a radiaciones ionizantes mediante la prueba de Giemsa en fluorescencia y utilizando bromodeoxiuridina y naranja de acridina.
Aim: The objective of this study was to describe the before and after cytogenetic aberrations found in current patients of radiotherapy. This can be observed through the technique called "Giemsa in fluorescence" Methods: A minimum of 200 metaphases were analyzed in the first mitotic division in 9 patients. The patients where observed before and after radiotherapy treatment at the San Juan de Dios Hospital in Costa Rica. In each case any type of chromosomopathy was counted using the "Giemsa in fluorescence" test as well as Bromodeoxyuridine and acridine orange. Results: The chromosomopathies are observed before and after treatment with radiotherapy. The treatment seems to change the frecuency increasing the dicentric chromosomes and centric rings after the treatment. The frequency of chromatid fractures satellite associations and morphological alterations were not affected by radiotherapy. Conclusion: The chromosomopathies produced by radiotherapy were observed both before and after treatment with variations in their frequency. After radiotherapy dicentric chromosomes and dicentric chromosomes plus rings frequencies increased significantly. A low mitotic count was present this could have been the result of radiation on the bone marrow or by the cell repair and apoptosis system. The standardized " Fluorescence Plus Giemsa" test using Bromodesoxyuridine and acridine orange was used for the fiesta time in Costa Reica. This allowed for the measurement of radiation exposure used in the treatment or detection of diseases and cancer in pacients.
ABSTRACT
ABSTRACT Purpose: To systematically examine the dynamic changes and time sequence in corneal epithelial cell apoptosis after excessive ultraviolet B irradiation. Methods: Ultraviolet B (144 mJ/cm2) was used to irradiate rat corneal epithelial cells for 2 h. Cell morphology was observed on differential interference contrast microscopy, and the numbers of the different kinds of apoptotic cells were counted using the ImageJ software. Cell viability was measured with the 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2-H-tetrazolium bromide method. Cell apoptotic rate and loss of mitochondrial membrane potential were detected using flow cytometric analyses. The expression levels of 3 apoptotic genes were measured with real-time quantitative polymerase chain reaction at different time points within 0-24 h after irradiation. Results: After 144-mJ/cm2 ultraviolet B irradiation for 2 h, the expression levels of caspase-8 and Bax were highest at 0 h; furthermore, the mitochondrial membrane potential decreased at 0 h and remained constant for 6 h in a subsequent culture. At 6 h, caspase-3 was activated. The decrease in cell viability and increase in apoptotic rate peaked at 6 h. The caspase-3 expression level decreased within 12-24 h, which led to a decline in apoptotic rate and change in apoptotic stage. Conclusions: The corneal epithelial cells exhibited rapid apoptosis after ultraviolet B irradiation, which was associated with both extrinsic and intrinsic pathways.
RESUMO Objetivos: Explorar sistematicamente as mudanças dinâmicas e a sequência temporal no processo de apoptose de células epiteliais corneanas após excesso de irradiação com ultravioleta B. Métodos: A radiação ultravioleta B (144 mJ/cm2) foi utilizada para irradiar células epiteliais da córnea de rato durante 2h. A morfologia celular foi observada por meio de microscópio de contraste de interferência diferencial, e os números de diferentes tipos de células apoptóticas foram contados e registrados pelo software ImageJ. A viabilidade celular foi medida pelo método brometo de 3- (4, 5-dimetil-2-tiazolil) -2, 5-difenil-2-H-tetrazólio. A taxa apoptótica celular e a perda do potencial da membrana mitocondrial foram detectadas por meio de análises citométricas de fluxo. Os níveis de expressão de três genes apoptóticos foram medidos por reação em cadeia da polimerase quantitativa em tempo real em diferentes momentos dentro de 0-24 h após a irradiação. Resultados: Após 144 mJ/cm2 de irradiação com ultravioleta B por 2h, os níveis de expressão de caspase-8 e Bax foram maiores em 0h; o potencial da membrana mitocondrial diminuiu a 0h e permaneceu constante por 6h na cultura subsequente. Às 6h, a caspase-3 foi ativada. A diminuição da viabilidade celular e o aumento da taxa apoptótica atingiu o pico em 6h. A expressão de caspase-3 diminuiu dentro de 12 - 24 h, levando a um declínio na taxa apoptótica e alteração no estágio apoptótico. Conclusões: As células epiteliais da córnea apresentaram uma apoptose rápida após excesso de irradiação com ultravioleta B, e esse processo foi associado tanto à via extrínseca como à via intrínseca.
ABSTRACT
Background: Radiation-induced hypothyroidism (RIH) is common after neck irradiation, and biochemical evaluation of thyroid function is recommended periodically for early diagnosis and treatment. This study aimed to evaluate the predictors of RIH after completion of adjuvant radiotherapy (RT) for primary oral squamous cell carcinoma (OSCC). Methods: This is a retrospective study involving 195 patients who received RT after surgery for OSCC between August 2011 and December 2016. Thyroid function tests were obtained every 6 months and patients were considered to be hypothyroid if thyroid-stimulating hormone level was >5 mIU/mL. Results: The study cohort comprised 130 men with a median age of 52 years (range 21–77 years). About 107 (54.87%) patients developed hypothyroidism, with a median of 21 months (range 2–67 months) for the development of RIH. Women [41 (63.1%) versus 66 (50.8%), p=0.035], addition of chemotherapy [36 (63.2%) versus 71 (51.4%), p= 0.019], and higher cumulative dose to the thyroid gland (median dose 4690 cGy versus 2981 cGy, P < 0.001) resulted in higher incidence of RIH on univariate analysis. On multivariate Cox regression analysis, female sex (P = 0.042), bilateral irradiation (P = 0.046), and cumulative dose to the thyroid (P = 0.001) were factors associated with increased risk of developing RIH. Conclusion: The addition of chemotherapy, high dose of radiation to the thyroid gland, bilateral irradiation, and female sex were at higher risk of developing RIH. However, more studies are required to identify the dose-volume constraints of the thyroid gland