scholarly journals Exosomal Small RNA Sequencing Uncovers Dose-Specific MiRNA Markers for Ionizing Radiation Exposure

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092673 ◽  
Author(s):  
Ying Zhang ◽  
Jiabin Liu ◽  
Liang Zhou ◽  
Shuai Hao ◽  
Zhenhua Ding ◽  
...  

Introduction: Acute exposure to ionizing radiation (IR) is hazardous or even lethal. Accurate estimation of the doses of IR exposure is critical to wisely determining the following treatments. Exosomes are nanoscale vesicles harboring biomolecules and mediate the communications among cells and tissues to influence biological processes. Screening out the microRNAs (miRNAs) contained in exosomes as biomarkers can be useful for estimating the IR exposure doses and exploring the correlation between these miRNAs and the occurrence of disease. Methods: We treated mice with 2.0, 6.5, and 8.0 Gy doses of IR and collected the mice sera at 0, 24, 48, and 72 hours after exposure. Then, the serum exosomes were isolated by ultracentrifuge and the small RNA portion was extracted for sequencing and the following bioinformatics analysis. Qualitative polymerase chain reaction was performed to validate the potential dose-specific markers. Results: Fifty-six miRNAs (31 upregulated, 25 downregulated) were differentially expressed after exposure of the above 3 IR doses and may act as common IR exposure miRNA markers. Bioinformatic analysis also identified several dosage-specific responsive miRNAs. Importantly, IR-induced miR-151-3p and miR-128-3p were significantly and stably increased at 24 hours in different mouse strains with distinct genetic background after exposed to 8.0 Gy of IR. Conclusion: Our study shows that miR-151-3p and miR-128-3p can be used as dose-specific biomarkers of 8.0 Gy IR exposure, which can be used to determine the exposure dose by detecting the amount of the 2 miRNAs in serum exosomes.

Author(s):  
Ricardo A. Chávez Montes ◽  
Fabiola Jaimes-Miranda ◽  
Stefan de Folter

Epigenomics ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1405-1418
Author(s):  
Xiaoyan Han ◽  
Lei Cai ◽  
Yi Lu ◽  
Dan Li ◽  
Jin Yang

Aim: To illustrate the expression profile of transfer RNA-derived fragments and reveal their putative role in the pathogenesis of diabetic cataract (DC) rats. Materials & methods: Small RNA sequencing was conducted in the lens epithelium of rats lens. The data were validated by quantitative real-time PCR, and bioinformatic analysis was performed to explore the roles of the fragments in DC pathogenesis. Results: A total of 213 differentially expressed tRNA-related fragments were identified, in which 111 were upregulated and 102 were downregulated in DC rats. Bioinformatics analysis revealed that several associated pathways might participate in the development of DC rats. Conclusion: tRNA-derived fragments may be involved in the pathogenesis of DC rats.


2019 ◽  
Vol 41 (5) ◽  
pp. 582-590 ◽  
Author(s):  
Yingyi Zhang ◽  
Ting Han ◽  
Dan Feng ◽  
Jie Li ◽  
Meihong Wu ◽  
...  

Abstract Gastric cancer remains one of the most lethal and prevalent malignancies, particularly in China. The majority of patients are diagnosed with gastric cancer at the late stages of the disease. Besides, the high relapse rate also contributes to the high mortality. Therefore, there exists an imperative need for the development of gastric cancer diagnostic techniques as well as novel indicators for gastric cancer metastasis. Exosomes, secreted by a variety of cell types, play critical roles in intercellular communication, which emerge as promising diagnostic biomarkers for gastric cancer. In this study, we present for the first time, at least to the best of our knowledge, the small RNA sequencing spectra of exosomes derived from the gastric cancer patient plasma using next-generation sequencing, focusing on the exploration of metastasis-related biomarkers. The exosomes enriched from patient plasma samples were well characterized by western blotting, transmission electron microscopy and nanoparticle-tracking analysis. In the following bioinformatic analysis of exosomal miRNAs, three candidates were proposed as the biomarkers for metastasis of gastric cancer, namely miR-10b-5p, miR-101-3p and miR-143-5p, for gastric cancer with lymph node metastasis, gastric cancer with ovarian metastasis and gastric cancer with liver metastasis, respectively. RT–qPCR was performed to test the accuracy of these candidates for validation. In conclusion, we successfully isolated and purified exosomes from plasma of patients with gastric cancer and identified several potential exosomal miRNA markers to distinguish gastric cancer patients with various kinds of metastasis.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xinhui Liu ◽  
Siqi Liu ◽  
Denggui Luo ◽  
Shiying Huang ◽  
Fochang Wang ◽  
...  

Jian-Pi-Yi-Shen formula (JPYSF) is a traditional Chinese medicine (TCM) formula used in clinic to treat chronic kidney disease (CKD) for decades. However, the mechanisms of JPYSF in treating CKD have not been fully elucidated. The aim of the present study was to test the renoprotective effect of JPYSF on CKD rat model and investigate the potential mechanism from the perspective of serum exosomal microRNAs (miRNAs). CKD rat model was induced by feeding Sprague-Dawley rats a diet containing 0.75% w/w adenine for four weeks. The rats in the treatment group were given 10.89 g/kg JPYSF by gavage every day, starting from the 3rd week of the adenine-containing diet for six weeks. Serum biochemistry and histopathology were used to evaluate the renoprotective effects of JPYSF. Serum exosomes were isolated by ExoQuick-TC PLUS exosomes extraction kit and were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Exosomal miRNAs profiling was analyzed by small RNA sequencing. The results showed that JPYSF treatment significantly lowered serum creatinine and blood urea nitrogen levels and alleviated renal pathological injury in CKD rats. Furthermore, serum exosomes were successfully isolated and identified. Small RNA sequencing revealed that 4 exosomal miRNAs (miR-192-5p, miR-194-5p, miR-802-5p, and miR-143-3p) were significantly downregulated in the CKD group and were markedly upregulated after JPYSF treatment. At last, miR-192-5p was identified as the most relevant miRNA for CKD diagnosis and JPYSF treatment. In conclusion, JPYSF protects kidney from adenine-induced CKD, which may be associated with modulation of exosomal miRNAs.


2020 ◽  
Vol 13 (2) ◽  
pp. 117-122
Author(s):  
Sandeep Shankar ◽  
Deepak Padmanabhan ◽  
Avinash Chandrashekharaiah ◽  
Saurabh Deshpande

Clinical diagnosis sometimes involves the use of medical instruments that employ ionizing radiation. However, ionizing radiation exposure is a workplace hazard that goes undetected and is detrimental to patients and staff in the catheterization laboratory. Every possible effort should be made to reduce the amount of radiation, including scattered radiation. Implementing radiation dose feedback may have a role in reducing exposure. In medicine, it is important to estimate the potential biologic effects on, and the risk to, an individual. In general, implantation of cardiac resynchronization devices is associated with one of the highest operator exposure doses due to the proximity of the operator to the radiation source. All physicians should work on the principle of as low as reasonably achievable. Methods for reducing radiation exposure must be implemented in the catheterization laboratory. In this article, we review the available tools to lower the radiation exposure dose to the operator during diagnostic, interventional, and electrophysiological cardiac procedures.


2008 ◽  
Vol 63 (1) ◽  
pp. 230-233
Author(s):  
Elżbieta Czekajska-Chehab ◽  
Piotr Przybylski ◽  
Marcin Pankowicz ◽  
Maria Korzec ◽  
Andrzej Drop

Genes ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 408 ◽  
Author(s):  
Jing-Yao Yu ◽  
Zhan-Guo Zhang ◽  
Shi-Yu Huang ◽  
Xue Han ◽  
Xin-Yu Wang ◽  
...  

Soybeans are an important cash crop and are widely used as a source of vegetable protein and edible oil. MicroRNAs (miRNA) are endogenous small RNA that play an important regulatory role in the evolutionarily conserved system of gene expression. In this study, we selected four lines with extreme phenotypes, as well as high or low protein and oil content, from the chromosome segment substitution line (CSSL) constructed from suinong (SN14) and ZYD00006, and planted and sampled at three stages of grain development for small RNA sequencing and expression analysis. The sequencing results revealed the expression pattern of miRNA in the materials, and predicted miRNA-targeted regulatory genes, including 1967 pairs of corresponding relationships between known-miRNA and their target genes, as well as 597 pairs of corresponding relationships between novel-miRNA and their target genes. After screening and annotating genes that were targeted for regulation, five specific genes were identified to be differentially expressed during seed development and subsequently analyzed for their regulatory relationship with miRNAs. The expression pattern of the targeted gene was verified by Real-time Quantitative PCR (RT-qPCR). Our research provides more information about the miRNA regulatory network in soybeans and further identifies useful genes that regulate storage during soy grain development, providing a theoretical basis for the regulation of soybean quality traits.


2020 ◽  
pp. 109158182096151
Author(s):  
Jennifer C. Shing ◽  
Kai Schaefer ◽  
Shaun E. Grosskurth ◽  
Andy H. Vo ◽  
Tatiana Sharapova ◽  
...  

Predictive indicators of testicular toxicity could improve drug development by allowing early in-life screening for this adverse effect before it becomes severe. We hypothesized that circulating microRNAs (miRNAs) could serve as testicular toxicity biomarkers in dogs. Herein, we describe the results of an exploratory study conducted to discover biomarkers of drug-induced testicular injury. Following a dose-selection study using the testicular toxicant ethylene glycol monomethyl ether (EGME), we chose a dose of 50 mg/kg/d EGME to avoid systemic toxicity and treated 2 groups of dogs (castrated, non-castrated) for 14 to 28 days. Castrated animals were used as negative controls to identify biomarkers specific for testicular toxicity because EGME can cause toxicity to organ systems in addition to the testis. Blood was collected daily during the dosing period, followed by recovery for 29 to 43 days with less frequent sampling. Dosing was well tolerated, resulting in mild-to-moderate degeneration in testes and epididymides. Global profiling of serum miRNAs at selected dosing and recovery time points was completed by small RNA sequencing. Bioinformatics data analysis using linear modeling demonstrated several circulating miRNAs that were differentially abundant during the dosing period compared with baseline and/or castrated control samples. Confirmatory reverse transcription quantitative polymerase chain reaction data in these animals was unable to detect sustained alterations of miRNAs in serum, except for 1 potential candidate cfa-miR-146b. Taken together, we report the results of a comprehensive exploratory study and suggest future directions for follow-up research to address the challenge of developing diagnostic biomarkers of testicular toxicity.


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