Urinary Nucleosides and Deoxynucleosides

Patejko, Małgorzata; Struck-Lewicka, Wiktoria; Siluk, Danuta; Waszczuk-Jankowska, Małgorzata; Markuszewski, Michał J.

doi:10.1016/bs.acc.2017.10.001

Cited by 15 publications

(15 citation statements)

References 119 publications

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“…Furthermore, increased nucleotides and deoxynucleotides in the serum suggests higher RNA turnover and DNA degradation possibly due to apoptosis of host cells or immune cells. Consistent with previous reports, RNA turnover and DNA degradation are increased in inflammatory diseases [ 40 , 41 ]. The role of increased (deoxy)nucleotides in the pathogenesis of pneumonia requires further research; however, it is possible that higher levels of nucleotides lead to unbalanced deoxyribonucleotide pools which, in turn, contribute to the progression to severe CAP.…”

Section: Discussionsupporting

confidence: 93%

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia

Wang

Huang

et al. 2023

Crit Care

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Objective Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. Methods Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. Results The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. Conclusion The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

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Section: Discussionsupporting

confidence: 93%

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia

Wang

Huang

et al. 2023

Crit Care

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“…Adenosine has been hyperpolarized by 2 in a SABRE experiment [22], and adenosine detection by hyperpolarized chemosensing has been demonstrated in urine SPE extracts [6] and minimally altered urine [7]. In terms of (bio)analytical utility, the concentrations of adenosine and its methylated derivatives in urine correlate to increased protein turnover in several pathological processes [23], including tumors [24]. The urine of cancer patients is expected to contain elevated concentrations of methylated adenosines [25], such as 1-methyladenosine 1b (Table 1).…”

Section: Analytical Value Of Adenosine Derivativesmentioning

confidence: 99%

Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives

2022

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Parahydrogen hyperpolarization has emerged as a promising tool for sensitivity-enhanced NMR metabolomics. It allows resolution and quantification of NMR signals of certain classes of low-abundance metabolites that would otherwise be undetectable. Applications have been implemented in pharmacokinetics and doping drug detection, demonstrating the versatility of the technique. Yet, in order for the method to be adopted by the analytical community, certain limitations have to be understood and overcome. One such question is NMR signal assignment. At present, the only reliable way to establish the identity of an analyte that gives rise to certain parahydrogen hyperpolarized NMR signals is internal standard addition, which can be laborious. Herein we show that analogously to regular NMR metabolomics, generating libraries of hyperpolarized analyte signals is a viable way to address this limitation. We present hyperpolarized spectral data of adenosines and give an early example of identifying them from a urine sample with the small library. Doing so, we verify the detectability of a class of diagnostically valuable metabolites: adenosine and its derivatives, some of which are cancer biomarkers, and some are central to cellular energy management (e.g., ATP).

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“…Nucleosides are produced by the degradations of DNA or RNA, and modified nucleosides are produced by enzymes such as methyltransferase and ligases after transcription 2 . Normal and modified nucleosides are released to urine and serum as a result of RNA turnover and DNA oxidative stress 3,4 . In particular, t‐RNA contains many normal and modified nucleosides, thus, nucleoside levels in urine and serum reflect t‐RNA turnover 2 .…”

Section: Introductionmentioning

confidence: 99%

“…In particular, t‐RNA contains many normal and modified nucleosides, thus, nucleoside levels in urine and serum reflect t‐RNA turnover 2 . In the presence of malignant disease, cell activities and growth are accelerated and nucleoside levels are elevated due to increased RNA turnover 4 . Therefore, normal nucleosides (adenosine, guanosine, cytidine, uridine) and modified nucleosides have been studied as potential biomarkers of cancer, lymphoma, rheumatoid arthritis, and various metabolic diseases 5–14 .…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Study of Normal and Modified Nucleosides in the Urine of Mice with Lipopolysaccharide‐Induced Sepsis by LC–MS/MS

Lee

Kim

et al. 2021

Bulletin Korean Chem Soc

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Endogenous normal and modified nucleosides have been studied as potential biomarkers of various inflammatory diseases including sepsis. However, no systematic nucleoside profiling and pattern analysis study has been performed in sepsis. In this study, simultaneous liquid chromatography–mass spectrometry profiling of normal and modified nucleosides was performed to characterize altered nucleoside metabolism in sepsis mice.

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Urinary Nucleosides and Deoxynucleosides

Cited by 15 publications

References 119 publications

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia

Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives

Metabolomic Study of Normal and Modified Nucleosides in the Urine of Mice with Lipopolysaccharide‐Induced Sepsis by LC–MS/MS

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