scholarly journals Circulating tRNA-Derived Small RNAs as Novel Radiation Biomarkers of Heavy Ion, Proton and X-ray Exposure

2021 ◽  
Vol 22 (24) ◽  
pp. 13476
Author(s):  
Wenjun Wei ◽  
Hao Bai ◽  
Yaxiong Chen ◽  
Tongshan Zhang ◽  
Yanan Zhang ◽  
...  

The effective and minimally invasive radiation biomarkers are valuable for exposure scenarios in nuclear accidents or space missions. Recent studies have opened the new sight of circulating small non-coding RNA (sncRNA) as radiation biomarkers. The tRNA-derived small RNA (tsRNA) is a new class of sncRNA. It is more abundant than other kinds of sncRNAs in extracellular vesicles or blood, presenting great potential as promising biomarkers. However, the circulating tsRNAs in response to ionizing radiation have not been reported. In this research, Kunming mice were total-body exposed to 0.05–2 Gy of carbon ions, protons, or X-rays, and the RNA sequencing was performed to profile the expression of sncRNAs in serum. After conditional screening and validation, we firstly identified 5 tsRNAs including 4 tRNA-related fragments (tRFs) and 1 tRNA half (tiRNA) which showed a significant level decrease after exposure to three kinds of radiations. Moreover, the radiation responses of these 5 serum tsRNAs were reproduced in other mouse strains, and the sequences of them could be detected in serum of humans. Furthermore, we developed multi-factor models based on tsRNA biomarkers to indicate the degree of radiation exposure with high sensitivity and specificity. These findings suggest that the circulating tsRNAs can serve as new minimally invasive biomarkers and can make a triage or dose assessment from blood sample collection within 4 h in exposure scenarios.

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3022 ◽  
Author(s):  
Walter Tinganelli ◽  
Marco Durante

Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue) and be exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and a reduced oxygen enhancement ratio compared to X-rays. Some radiobiological properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different “drug” in oncology, and may elicit favorable responses such as an increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results.


Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582091417 ◽  
Author(s):  
Wenjun Wei ◽  
Hao Bai ◽  
Xiu Feng ◽  
Junrui Hua ◽  
Kaiqin Long ◽  
...  

Exposure to ionizing radiation is a major threat to human health and public security. Since the inherent limitations of current methods for indicating radiation exposure, new minimally invasive biomarkers that can be easily and quickly detected at an early stage are needed for optimal medical treatment. Serum proteins are attractive biomarkers and some radiosensitive proteins have been found, but the proteins in response to low-dose and high-linear energy transfer (LET) radiation have not been reported. In this study, mice were whole body exposed to a variety doses of carbon ions and X-rays. We performed Mouse Antibody Array to detect serum proteins expression profiles at 24 hours postirradiation. After conditional screening, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 were further validated using enzyme-linked immunosorbent assay. After exposure to 0.05 to 1 Gy of carbon ions and 0.5 to 4 Gy of X-rays, only IGFBP-3 showed obvious increase with increased doses, both carbon ions and X-rays. Further, IGFBP-3 was detected for observation of its time-dependent changes. The results showed the expression difference of IGFBP-3 presented from 6 to 24 hours post-irradiation by carbon ions and X-rays. Moreover, the receiver–operating characteristic analysis showed that serum IGFBP-3 is efficient to triage exposed individuals with high sensitivity and specificity. These results suggest that serum IGFBP-3 is extremely sensitive to high- and low-LET ionizing radiation and is able to respond at an early stage, which could serve as a novel minimally invasive indicator for radiation exposure.


Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878984
Author(s):  
Yong Chen ◽  
Haining Gao ◽  
Wenling Ye

Heavy-ion irradiation-induced nuclear DNA damage and mutations have been studied comprehensively. However, there is no information about the deleterious effect of heavy-ion irradiation on mitochondrial DNA (mtDNA). In this study, 2 typical mtDNA mutations were examined, including 4977 deletions and D310 point mutations. The 4977 deletions were quantified by real-time polymerase chain reaction, and D310 point mutations were analyzed by direct sequencing and a specific enzyme digestion genotyping method. Results showed that carbon ions radiation can induce temporal fluctuation of mtDNA 4977 deletions in 72 hours after irradiation, while survived clones were free from this deletion. Carbon ions induced more D310 mutations than X-rays, and the single-cell heteroplasmy was eliminated. This is the first study investigating mtDNA mutations induced by carbon ions irradiation in vitro. These findings would provide fundamental information for further investigation of radiation-induced mitochondrial biogenesis.


Author(s):  
Walter Tinganelli ◽  
Marco Durante

Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy is irradiated with protons, which have physical advantages compared to X-rays but similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue), and being exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and reduced oxygen enhancement ratio compared to X-rays. Some radiobiology properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different “drug” in oncology, and may elicit favorable responses such as increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results.


Author(s):  
D. A. Carpenter ◽  
M. A. Taylor

The development of intense sources of x rays has led to renewed interest in the use of microbeams of x rays in x-ray fluorescence analysis. Sparks pointed out that the use of x rays as a probe offered the advantages of high sensitivity, low detection limits, low beam damage, and large penetration depths with minimal specimen preparation or perturbation. In addition, the option of air operation provided special advantages for examination of hydrated systems or for nondestructive microanalysis of large specimens.The disadvantages of synchrotron sources prompted the development of laboratory-based instrumentation with various schemes to maximize the beam flux while maintaining small point-to-point resolution. Nichols and Ryon developed a microprobe using a rotating anode source and a modified microdiffractometer. Cross and Wherry showed that by close-coupling the x-ray source, specimen, and detector, good intensities could be obtained for beam sizes between 30 and 100μm. More importantly, both groups combined specimen scanning with modern imaging techniques for rapid element mapping.


Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 363
Author(s):  
Vânia M. Moreira ◽  
Paulo Mascarenhas ◽  
Vanessa Machado ◽  
João Botelho ◽  
José João Mendes ◽  
...  

The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling techniques, yet, these have some limitations such as the complexity of collection. Hence, several other types of specimens that are easier to obtain are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab (CS) against standard specimens (NPS, OPS, or a combination of both). In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30th of December, 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2). We identified 1560 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0–98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4–88.8) and specificity of 96.4% (95% CI: 89.5–98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3–95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3–96.9) and specificity of 63.1% (95% CI: 36.8–89.3). The remaining index specimens could not be adequately assessed given the lack of studies available. Our meta-analysis shows that saliva samples from the oral region provide a high sensitivity and specificity; therefore, these appear to be the best candidates for alternative specimens to NPS/OPS in SARS-CoV-2 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial, since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or at outbreak control spots (e.g., schools, airports, and nursing homes).


1998 ◽  
Vol 4 (S2) ◽  
pp. 378-379
Author(s):  
Z. W. Chen ◽  
D. B. Wittry

A monochromatic x-ray microprobe based on a laboratory source has recently been developed in our laboratory and used for fluorescence excitation. This technique provides high sensitivity (ppm to ppb), nondestructive, quantitative microanalysis with minimum sample preparation and does not require a high vacuum specimen chamber. It is expected that this technique (MMXRF) will have important applications in materials science, geological sciences and biological science.Three-dimensional focusing of x-rays can be obtained by using diffraction from doubly curved crystals. In our MMXRF setup, a small x-ray source was produced by the bombardment of a selected target with a focused electron beam and a toroidal mica diffractor with Johann pointfocusing geometry was used to focus characteristic x-rays from the source. In the previous work ∼ 108 photons/s were obtained in a Cu Kα probe of 75 μm × 43 μm in the specimen plane using the fifth order reflection of the (002) planes of mica.


1998 ◽  
Vol 159 (2) ◽  
pp. 275-280 ◽  
Author(s):  
JG Gonzalez-Gonzalez ◽  
NE De la Garza-Hernandez ◽  
LG Mancillas-Adame ◽  
J Montes-Villarreal ◽  
JZ Villarreal-Perez

The short cosyntropin (synthetic ACTH) test is recognized as the best screening manoeuvre in the assessment of adrenocortical insufficiency. Recent data, however, suggest that i.v. administration of 250 microg cosyntropin could be a pharmacological rather than a physiological stimulus, losing sensitivity for detecting adrenocortical failure. Our objective was to compare 10 vs 250 microg cosyntropin in order to find differences in serum cortisol peaks in healthy individuals, the adrenocortical response in a variety of hypothalamic-pituitary-adrenal axis disorders and the highest sensitivity and specificity serum cortisol cut-off point values. The subjects were 83 healthy people and 37 patients, the latter having Addison's disease (11), pituitary adenomas (7), Sheehan's syndrome (9) and recent use of glucocorticoid therapy (10). Forty-six healthy subjects and all patients underwent low- and standard-dose cosyntropin testing. In addition, 37 controls underwent the low-dose test. On comparing low- and standard-dose cosyntropin testing in healthy subjects there were no statistical differences in baseline and peaks of serum cortisol. In the group of patients, 2 out of 11 cases of Addison's disease showed normal cortisol criterion values during the standard test but abnormal during the low-dose test. In our group of patients and controls, the statistical analysis displayed a better sensitivity of the low-dose vs standard-dose ACTH test at 30 and 60 min. In conclusion, these results suggest that the use of 10 microg rather than 250 microg cosyntropin i.v. in the assessment of suspicious adrenocortical dysfunction gives better results.


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