scholarly journals Identification of lncRNA, MicroRNA, and mRNA-Associated CeRNA Network of Radiation-Induced Lung Injury in a Mice Model

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989101
Author(s):  
Yida Li ◽  
Liqing Zou ◽  
Xi Yang ◽  
Li Chu ◽  
Jianjiao Ni ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lung Injury ◽  
Early Stage ◽  
Cell Lineage ◽  
Late Complications ◽  
Control Group ◽  
Messenger Rnas ◽  
Mice Model ◽  
Target Mrnas ◽  
Radiation Induced

Radiation-induced lung injury (RILI) can be challenging for thoracic radiotherapy, thus investigating its mechanisms of related pathophysiological process is needed. Long noncoding RNAs (lncRNAs) was found to participate in normal tissue damage induced by ionizing irradiation. Here, we first profiled the dysregulation of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) of RILI in mice model receiving 12 Gy thoracic irradiation. The lung tissue was collected 48 hours after irradiation, after which an RNA library was built by RNA sequencing. Compared with the control group, 461 mRNAs and 401 lncRNAs were significantly upregulated, while 936 mRNAs and 501 lncRNAs were significantly downregulated. Then we predicted target miRNAs of the dysregulated lncRNAs and the target mRNAs of these miRNAs. Next, functional annotations of these target mRNAs were performed. Results showed some pathways apparently dysregulated, such as Th1 and Th2 cell differentiation, Th17 cell differentiation, and hematopoietic cell lineage. Through this study, we also highlighted that T helpers could be vital in RILI through lncRNA-miRNA-mRNA network, therefore causing fibrosis, indicating that RNA dysregulation in early stage of RILI may cause severe late complications. Thus, research on the target mechanism and early intervention of lncRNAs with associated competing endogenous RNA network will benefit the treatment of RILI.

scholarly journals Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

2017 ◽  
Vol 58 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Jinmei Chen ◽  
Weijian Zhang ◽  
Lurong Zhang ◽  
Jiemin Zhang ◽  
Xiuying Chen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Glycyrrhetinic Acid ◽  
Control Group ◽  
X Rays ◽  
Radiation Induced ◽  
Tgf Β1

Abstract Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway.

scholarly journals Gata2-L359V impairs primitive and definitive hematopoiesis and blocks cell differentiation in murine chronic myelogenous leukemia model

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Ya-Kai Fu ◽  
Yun Tan ◽  
Bo Wu ◽  
Yu-Ting Dai ◽  
Xiao-Guang Xu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Rna Sequencing ◽  
Early Stage ◽  
Binding Capacity ◽  
Adult Life ◽  
Myelogenous Leukemia ◽  
Mice Model ◽  
Altered Expression ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Primitive Erythropoiesis

AbstractGATA2, a key transcription factor in hematopoiesis, is frequently mutated in hematopoietic malignancies. How the GATA2 mutants contribute to hematopoiesis and malignant transformation remains largely unexplored. Here, we report that Gata2-L359V mutation impeded hematopoietic differentiation in murine embryonic and adult hematopoiesis and blocked murine chronic myeloid leukemia (CML) cell differentiation. We established a Gata2-L359V knockin mouse model in which the homozygous Gata2-L359V mutation caused major defects in primitive erythropoiesis with an accumulation of erythroid precursors and severe anemia, leading to embryonic lethality around E11.5. During adult life, the Gata2-L359V heterozygous mice exhibited a notable decrease in bone marrow (BM) recovery under stress induction with cytotoxic drug 5-fluorouracil. Using RNA sequencing, it was revealed that homozygous Gata2-L359V suppressed genes related to embryonic hematopoiesis in yolk sac, while heterozygous Gata2-L359V dysregulated genes related to cell cycle and proliferation in BM Lin-Sca1+c-kit+ cells. Furthermore, through chromatin immunoprecipitation sequencing and transactivation experiments, we found that this mutation enhanced the DNA-binding capacity and transcriptional activities of Gata2, which was likely associated with the altered expression of some essential genes during embryonic and adult hematopoiesis. In mice model harboring BCR/ABL, single-cell RNA-sequencing demonstrated that Gata2-L359V induced additional gene expression profile abnormalities and partially affected cell differentiation at the early stage of myelomonocytic lineage, evidenced by the increase of granulocyte–monocyte progenitors and monocytosis. Taken together, our study unveiled that Gata2-L359V mutation induces defective hematopoietic development and blocks the differentiation of CML cells.

scholarly journals Identification and integrated analysis of CircRNA and miRNA of Radiation-Induced lung injury in a mice model

2020 ◽  
Author(s):  
Xi Yang ◽  
Yida Li ◽  
Liqing Zou ◽  
Li Chu ◽  
Luxi Ye ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Normal Lung ◽  
Future Research ◽  
Circular Rnas ◽  
Integrated Analysis ◽  
Mice Model ◽  
Radiation Induced

Abstract Radiation-induced lung injury (RILI) is a main threat to patients received thoracic radiotherapy, it is of great importance to understand the molecular mechanism of RILI. Circular RNAs (CircRNAs) have been found to act as the regulator of multiple biological processes and circRNA-miRNA-mRNA axis could play an important role in signaling pathway of many human diseases including radiation injury, here, we first investigate the circRNA and miRNA of radiation-induced lung injury in a mice model. The mice received 12 Gy thoracic irradiation and the irradiated lung tissues at 48 hours after irradiation were analyzed by RNA Sequencing (RNA-seq) technique compared with normal lung tissues. We identified 21 significantly up-regulated while significantly 33 down-regulated miRNAs. Among 27 differentially expressed circRNAs, 10 were down-regulated and 17 were up-regulated. We then performed circRNAs GO analysis of the target mRNAs of these significantly differently expressed circRNAs. These differentially expressed miRNAs took part in series of cellular processes such as positive regulation of alpha-beta T cell proliferation, interstitial matrix, collagen fibril organization, chemokine receptor activity, cellular defense response, and B cell receptor signaling pathway. Through this study, we found that immune-related molecular pathways play an important role in the early response after radiotherapy. In the future, research on the target mechanism and early intervention of circRNAs with associated miRNAs will benefit the treatment of RILI.

scholarly journals Inhibitory Effects of GGX on Lung Injury of Chronic Obstructive Lung Disease (COPD) Mice Model

2021 ◽  
Vol 42 (3) ◽  
pp. 56-71
Author(s):  
Tae Hyeon Kim ◽  
Won Kyung Yang ◽  
Su Won Lee ◽  
Seung Hyung Kim ◽  
Yee Ran Lyu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Disease ◽  
Lung Tissue ◽  
Obstructive Lung Disease ◽  
Chronic Obstructive Lung Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Chronic Obstructive ◽  
Mice Model ◽  
Tnf Α

Objectives: This study is aimed to evaluate the protective effects of GGX on lung injury of Chronic Obstructive Lung Disease (COPD) mice model. Materials and Methods: C57BL/6 mice were challenged with lipopolysaccharide (LPS) and cigarette smoke extract (CSE) and then treated with vehicle only (Control group), dexamethasone 3 ㎎/㎏ (Dexa group), gam-gil-tang 200 ㎎/㎏ (GGT group), GGX 100, 200, and 400 ㎎/㎏ (GGX group). After sacrifice, its bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed with cytospin, Enzyme-Linked Immunosorbent Assay (ELISA), real-time polymerase chain reaction (PCR) and hematoxylin & eosin (H&E), and Masson’s trichrome staining. Results: In the COPD model, GGX significantly inhibited the increase of neutrophils, TNF-α, IL-17A, CXCL-1, MIP2 in BALF and TNF-α, IL-1β, IL-10 mRNA expression in lung tissue. It also decreased the severity of histological lung injury. Conclusion: This study suggests the usability of GGX for COPD patients by controlling lung tissue injury.

Quantification of regional early stage gas exchange changes using hyperpolarized129Xe MRI in a rat model of radiation-induced lung injury

2016 ◽  
Vol 43 (5) ◽  
pp. 2410-2420 ◽  
Author(s):  
Ozkan Doganay ◽  
Elaine Stirrat ◽  
Charles McKenzie ◽  
Rolf F. Schulte ◽  
Giles E. Santyr
Keyword(s):  
Gas Exchange ◽  
Lung Injury ◽  
Rat Model ◽  
Early Stage ◽  
Radiation Induced

Early stage radiation-induced lung injury detected using hyperpolarized 129 Xe Morphometry: Proof-of-concept demonstration in a rat model

2015 ◽  
Vol 75 (6) ◽  
pp. 2421-2431 ◽  
Author(s):  
Alexei Ouriadov ◽  
Matthew Fox ◽  
Elaine Hegarty ◽  
Grace Parraga ◽  
Eugene Wong ◽  
...  
Keyword(s):  
Lung Injury ◽  
Rat Model ◽  
Early Stage ◽  
Proof Of Concept ◽  
Radiation Induced

Prevention and treatment of radiation-induced lung injury

2020 ◽  
Vol 12 (23) ◽  
pp. 2161-2173
Author(s):  
Chengcheng Xia ◽  
Weiyan Shi ◽  
Yuyu Zhang ◽  
Lijuan Ding ◽  
Ling Gao ◽  
...  
Keyword(s):  
Lung Injury ◽  
Cancer Patients ◽  
Radiation Pneumonitis ◽  
Early Stage ◽  
Treatment Options ◽  
Treatment And Prevention ◽  
Thoracic Radiation ◽  
Radiation Induced ◽  
Transplantation Conditioning

Radiation-induced lung injury (RILI) is a common complication in cancer patients receiving local thoracic radiation and bone marrow transplantation conditioning. It is divided into early-stage radiation pneumonitis and advanced radiation fibrosis of the lung. This severely hampers the quality of life and survival of cancer patients. Meanwhile, RILI is a major factor limiting radiation doses in clinical practice, which affects the local control of cancer. Unfortunately, the mechanism of RILI is still not well defined, and there are no treatment options available for these patients. In this review we summarize the methods and agents used for the treatment and prevention of RILI, with the aim of increasing understanding of RILI.

scholarly journals Serum Metabolomic Analysis of Radiation-Induced Lung Injury in Rats

Dose-Response ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 155932582110670
Author(s):  
Yahui Feng ◽  
Yiying Gao ◽  
Wenling Tu ◽  
Yang Feng ◽  
Jianping Cao ◽  
...  
Keyword(s):  
Lung Injury ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Sprague Dawley ◽  
Rat Serum ◽  
Cancer Breast ◽  
Sprague Dawley Rats ◽  
Benzyl Thiocyanate ◽  
Significant Enrichment ◽  
Radiation Induced

Radiation-induced lung injury is a common complication of radiotherapy for lung cancer, breast cancer, esophageal cancer, and thymoma. This study aims to illustrate biomarkers of radiation-induced lung injury and its potential mechanism through the study of metabolomic alterations in serum of Sprague-Dawley rats with different radiation doses. Serum from 0, 10, or 20 Gy irradiated rats were collected and subjected to gas chromatography-mass spectrometry. The result showed that there were 23 dysregulated metabolites between the 10 Gy irradiation group and the 0 Gy control group, whereas 36 preferential metabolites were found between the 20 Gy irradiated rat serum and the control groups. Among them, there were 19 common differential metabolites in the 2 irradiation groups, including 3 downregulated (benzyl thiocyanate, carbazole, and N-formyl-L-methionine) and 16 upregulated metabolites. We further analyzed the metabolic pathways of different metabolites; the results showed that there were 3 significant enrichment pathways in the 10 Gy vs 0 Gy group and 7 significant enrichment pathways in the 20 Gy vs 0 Gy group. Among them, taurine and hypotaurine metabolism, riboflavin metabolism, and glyoxylate and dicarboxylate metabolism were the common metabolic enrichment pathways of the 10 Gy vs 0 Gy group and the 20 Gy vs 0 Gy group.

scholarly journals Analysis of cardiac and pulmonary complication probabilities after radiation therapy for patients with early-stage breast cancer

Medicina ◽  
2009 ◽  
Vol 45 (4) ◽  
pp. 276 ◽  
Author(s):  
Olga Utehina ◽  
Sergejs Popovs ◽  
Dace Purina ◽  
Ingrida Slosberga ◽  
Ilga Vevere ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Pulmonary Complication ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Postoperative Treatment ◽  
Control Group ◽  
Cardiac Mortality ◽  
Breast Irradiation ◽  
Radiation Induced

Objective. The purpose of this study was to evaluate the radiobiological implications of clinical use of respiratory-gated techniques for postoperative radiation therapy of early-stage left-sided breast cancer after breast-conserving surgery. Material and methods. Radiation therapy treatment plans of 80 patients with early-stage breast cancer (stage I–II), receiving whole breast irradiation after breast-conserving therapy, were analyzed. The control group consisting of 47 patients received standard radiation therapy, and the respiratory-gated group consisting of 33 patients received deep inspiration-gated radiation therapy. Normal tissue complication probabilities (NTCP) for cardiac mortality and for clinical radiation-induced pneumonitis were calculated for all patients included in present study, using relative seriality model. NTCP data were analyzed for 113 radiation therapy plans, which included free breathing plans for the respiratory-gated groups. Results. Pneumonitis probability was 0.6% (range 0.0–2.8%) and 0.3% (0.0–1.2%) for control and respiratory-gated group, respectively. Cardiac mortality was 1.3% (0.0–5.0%) and 0.2% (0.0–2.8%) for control and respiratory-gated group, respectively. Using respiratory-gated radiation therapy, NTCP was reduced in comparison with the control group by 83% (P<0.00001) and by 55% (P=0.01270) for cardiac mortality and for clinical radiation-induced pneumonitis, respectively. Conclusions. Use of respiratory-gated radiation therapy, for postoperative treatment of earlystage breast cancer, significantly reduces excessive cardiac mortality probability and pulmonary complication probability, as compared to standard radiation therapy techniques. This is especially important from heart complication probability point of view, as cardiac mortality remains one of the important issues of postoperative breast irradiation in patients with early stage breast cance

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