Comprehensive Analysis of Serum Metabolites Profiles in Acute Radiation Enteritis Rats by Untargeted Metabolomics

Nie, He; Pan, Jiadong; An, Fangmei; Zheng, Chuwei; Zhan, Qiang

doi:10.1620/tjem.255.257

Cited by 5 publications

(8 citation statements)

References 31 publications

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“…While 2-oxoadipic acid is reported less often in the literature, it has been documented in the urine of Atm −/− mice 58 and also lower in the plasma of rats following a 10 Gy abdominal exposure. 22 It is a product of lysine metabolism via pipecolic acid metabolism, where pipecolic acid is the accumulated product typically reported after IR exposure. 58 Its specificity to LBI may be explained by the gut microbiota being shielded in the UBI group.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…24 At 4 days, several serum metabolites were significantly changed in rats from control animals following abdominal radiation; however, as no comparisons were made to TBI the interpretation for biodosimetry is limited. 22 Metabolite profiles can also be extrapolated to one to several month time points to aid in biomarkers of delayed effects of acute radiation exposure (DEARE), such as cardiac injury. 16 As these previous studies have indicated the utility of metabolomics to span both TBI and PBI scenarios for biodosimetry, they have been confined within conventional dose rates available from commercial instruments.…”

Section: ■ Introductionmentioning

confidence: 99%

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Impact of Partial Body Shielding from Very High Dose Rates on Untargeted Metabolomics in Biodosimetry

Pannkuk,

Laiakis,

Garty

et al. 2024

ACS Omega

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A realistic exposure to ionizing radiation (IR) from an improvised nuclear device will likely include individuals who are partially shielded from the initial blast delivered at a very high dose rate (VHDR). As different tissues have varying levels of radiosensitivity, e.g., hematopoietic vs gastrointestinal tissues, the effects of shielding on radiation biomarkers need to be addressed. Here, we explore how biofluid (urine and serum) metabolite signatures from male and female C57BL/6 mice exposed to VHDR (5−10 Gy/s) total body irradiation (TBI, 0, 4, and 8 Gy) compare to individuals exposed to partial body irradiation (PBI) (lower body irradiated [LBI] or upper body irradiated [UBI] at an 8 Gy dose) using a data-independent acquisition untargeted metabolomics approach. Although sex differences were observed in the spatial groupings of urine signatures from TBI and PBI mice, a metabolite signature (N6,N6,N6-trimethyllysine, carnitine, propionylcarnitine, hexosamine-valine-isoleucine, taurine, and creatine) previously developed from variable dose rate experiments was able to identify individuals with high sensitivity and specificity, irrespective of radiation shielding. A panel of serum metabolites composed from previous untargeted studies on nonhuman primates had excellent performance for separating irradiated cohorts; however, a multiomic approach to complement the metabolome could increase dose estimation confidence intervals. Overall, these results support the inclusion of small-molecule markers in biodosimetry assays without substantial interference from the upper or lower body shielding.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Impact of Partial Body Shielding from Very High Dose Rates on Untargeted Metabolomics in Biodosimetry

Pannkuk,

Laiakis,

Garty

et al. 2024

ACS Omega

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“…Last year, untargeted metabolomics was used by Nie et al . 19 in the analysis of serum metabolites in acute radiation enteritis rats. The results showed that o -aminobenzoic acid and hippuric acid were the most significant metabolites affected by radiation modeling, which were reduced nearly ten-fold in rats with acute radiation enteritis.…”

Section: Introductionmentioning

confidence: 99%

The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis

Zhou²,

Liu³

et al. 2023

Acta Pharmaceutica Sinica B

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“…The complexity and heterogeneity of ALI pathophysiology necessitate the employment of high-throughput technologies, such as metabolomics, for pinpointing potential diagnostic and prognostic biomarkers for AAD with ALI. Metabolomics facilitates a comprehensive quantitative evaluation of small molecule metabolites (typically <1,500 Daltons) in cells, tissues, or organisms, which provides a direct functional readout of the physiological or pathological state of an organism ( Nie et al, 2021 ). This study aims to leverage a metabolomics platform to identify diagnostic biomarkers for the early stage of AAD with ALI, address the perturbed pathways underlying disease progression, and illuminate the pathophysiological mechanisms of AAD with ALI.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection

Fan

Meng

et al. 2023

Front. Mol. Biosci.

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Introduction: Acute aortic dissection (AAD) often leads to the development of acute lung injury (ALI). However, the early detection and diagnosis of AAD in patients with ALI pose significant challenges. The objective of this study is to investigate distinct metabolic alterations in the plasma samples of AAD patients with ALI, AAD patients without ALI, and healthy individuals.Method: Between September 2019 and September 2022, we retrospectively collected data from 228 AAD patients who were diagnosed with ALI through post-surgery chest X-ray and PaO2/FiO2 assessments. Univariate analysis was employed to identify pre-surgery risk factors for ALI. Additionally, we conducted high-throughput target metabolic analysis on 90 plasma samples, comprising 30 samples from AAD patients with ALI, 30 from patients with AAD only, and 30 from healthy controls. After LC-MS spectral processing and metabolite quantification, the recursive feature elimination with cross-validation (RFECV) analysis based on the random forest was used to select the optimal metabolites as a diagnostic panel for the detection of AAD patients with ALI. The support vector machines (SVM) machine learning model was further applied to validate the diagnostic accuracy of the established biomarker panel.Results: In the univariate analysis, preoperative β-HB and TNF-α exhibited a significant association with lung injury (OR = 0.906, 95% CI 0.852–0.965, p = 0.002; OR = 1.007, 95% CI 1.003–1.011, p < 0.0001). The multiple-reaction monitoring analysis of 417 common metabolites identified significant changes in 145 metabolites (fold change >1.2 or <0.833, p < 0.05) across the three groups. Multivariate statistical analysis revealed notable differences between AAD patients and healthy controls. When compared with the non-ALI group, AAD patients with ALI displayed remarkable upregulation in 19 metabolites and downregulation in 4 metabolites. Particularly, combining citric acid and glucuronic acid as a biomarker panel improved the classification performance for distinguishing between the ALI and non-ALI groups.Discussion: Differentially expressed metabolites in the ALI group were primarily involved in amino acids biosynthesis, carbohydrate metabolism (TCA cycle), arginine and proline metabolism, and glucagon signaling pathway. These findings demonstrate a great potential of the targeted metabolomic approach for screening, routine surveillance, and diagnosis of pulmonary injury in patients with AAD.

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Comprehensive Analysis of Serum Metabolites Profiles in Acute Radiation Enteritis Rats by Untargeted Metabolomics

Cited by 5 publications

References 31 publications

Impact of Partial Body Shielding from Very High Dose Rates on Untargeted Metabolomics in Biodosimetry

Impact of Partial Body Shielding from Very High Dose Rates on Untargeted Metabolomics in Biodosimetry

The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis

Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection

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