<sup>1</sup>H NMR-Based Urine Metabolomics Reveals Signs of Enhanced Carbon and Nitrogen Recycling in Prostate Cancer

Bruzzone, Chiara; Loizaga-Iriarte, Ana; Sánchez-Mosquera, Pilar; Gil‐Redondo, Rubén; Astobiza, Ianire; Diercks, Tammo; Cortazar, Ana R.; Ugalde-Olano, Aitziber; Schäfer, Hartmut; Blanco, Francisco J.; Unda, Miguel; Cannet, Claire; Spraul, Manfred; Mato, José M.; Embade, Nieves; Carracedo, Arkaitz; Millet, Óscar

doi:10.1021/acs.jproteome.0c00091

Cited by 25 publications

(25 citation statements)

References 33 publications

(59 reference statements)

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“…NMR analysis showed that neither aminolevulinate nor porphobilinogen accumulate. 10 This signature is specific for COVID-19 patients and does not match the one found in porphyrias, specifically in those where the central enzymes of the haem pathway are malfunctioning due to deleterious mutations. 11,12 Instead, in COVID-19, it is hard to rationalize how the pathological haem shortage may affect its own regulation, while the reported hyperferritinaemia may be a consequence of the inflammation process.…”

Section: Resultsmentioning

confidence: 96%

Abnormal concentration of porphyrins in serum from COVID‐19 patients

et al. 2020

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COVID‐19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 is not only a lung disease but rather a systemic syndrome where blood alterations may play a key role (1). Severe cases show a marked variation in the red blood cell distribution width (2), which agrees well with reduced erythrocyte turnover and would function as a compensatory mechanism to maintain the circulating red blood cell and oxygen levels (3).

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Section: Resultsmentioning

confidence: 96%

Abnormal concentration of porphyrins in serum from COVID‐19 patients

et al. 2020

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“…Increased levels of acetate and inosine/adenosine have been reported in lung tissues compared with adjacent lung cancer tissues (47). Moreover, the acetate level was found to be reduced in the urine of patients with prostate cancer (52) in whom acetate might be used by cancer cells as a source of lipid biosynthesis in tumors (53). Moreover, the acetate level was found to be reduced in the feces of patients with colorectal cancer, which was caused by a disturbance of the intestinal microbiota and host tissues associated with colorectal tumorigenesis (17).…”

Section: Discussionmentioning

confidence: 98%

Metabolic Profiling of Praziquantel-mediated Prevention ofOpisthorchis viverrini-induced Cholangiocyte Transformation in the Hamster Model of Cholangiocarcinoma

Prommajun

Phetcharaburanin

Namwat

et al. 2021

Cancer Genomics Proteomics

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Background: Opisthorchis viverrini (Ov) infectioninduced cholangiocarcinoma (CCA) is a major public health problem in northeastern Thailand. Praziquantel was shown to prevent CCA development in an Ov-infected hamster model; however, the molecular mechanism remains unknown. Materials and Methods: In this study, we used a hamster model with Ov and N-nitrosodimethylamine-induced CCA to study the mechanisms of praziquantel action. The liver tissues from the hamsters with and without praziquantel treatment were analyzed using 1 H nuclear magnetic resonance spectroscopy. Results: A total of 14 metabolites were found to be significantly different between the two groups. Furthermore, the combination of acetate, inosine and sarcosine was shown to exert an anti-inflammatory effect through interleukin-6 inhibition in a macrophage cell line, suggesting a mechanism by which praziquantel may prevent inflammation caused by Ov, cholangiocyte transformation and further CCA develpoment. Conclusion: These findings might avail the development of a preventive strategy for CCA in high-risk populations.Cholangiocarcinoma (CCA), a malignancy of bile duct epithelial cells, is a major public health problem in Northeast Thailand, which has the highest incidence in the world of this disease (1). A parasitic infection caused by Opisthorchis viverrini (Ov), a liver fluke, was identified as a cause of CCA in 1994 and is associated with CCA development (1). Upon liver fluke infection, CCA genesis is hypothesized to be initially induced via multiple mechanistic pathways, including mechanical damage caused by the fluke suckers, fluke toxic secretory products, and the host immunopathological response, leading to chronic inflammation (2). Moreover, the overproduction of reactive oxygen species and reactive nitrogen species from chronic inflammation results in tissue injury associated with CCA initiation and progression (3). In accordance with the hepatic changes first reported in 1978 in an Ov-infected hamster model, hyperplasia, adenomatous formations and periductal and portal scarring of the bile duct epithelium were also observed at 22 weeks post infection, although bile duct carcinoma was not seen at that time (4). In addition, a previous study showed that alone, Nnitrosodimethylamine (NDMA), a potential carcinogen, did not induce tumor formation in hamsters, but together with Ov infection, CCA was observed in a number of animals (5). Furthermore, histological changes, such as inflammatory reactions, bile duct proliferation, periductal fibrosis and cholangiocarcinoma lesions, were all observed in this cotreatment group (5). At the gene-expression level, we have shown a single down-regulated and 23 up-regulated give transcripts that were involved in Ov-induced CCA development (6). The up-regulated genes include signal 29 This article is freely accessible online.

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“…NMR measurements. Experiments were performed as previously described (17,18). In brief, two complementary experiments were recorded per sample: a one-dimensional (1D) 1 H spectrum with water presaturation for metabolite quanti cation and a two-dimensional (2D) J-resolved 1 H spectrum.…”

Section: Methodsmentioning

confidence: 99%

A molecular signature for the Metabolic Syndrome by urine metabolomics

Bruzzone

Gil‐Redondo

Seco

et al. 2021

Preprint

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BACKGROUND. Metabolic syndrome (MetS) is a multimorbid long-term condition without consensual medical definition and a diagnostic based on compatible symptomatology. Here we have investigated the molecular signature of MetS in urine.METHODS. We used NMR-based metabolomics to investigate a European cohort including urine samples from 11,754 individuals (18–75 years old, 41% females), designed to populate all the intermediate conditions in MetS, from subjects without any risk factor up to individuals with developed MetS (4–5%, depending on the definition). A set of quantified metabolites were integrated from the urine spectra to obtain metabolic models (one for each definition), to discriminate between individuals with MetS.RESULTS. MetS progression produces a continuous and monotonic variation of the urine metabolome, characterized by up- or down-regulation of the pertinent metabolites (19 in total, including glucose, lipids, aromatic amino acids, salicyluric acid, maltitol, trimethylamine N-oxide, and p-cresol sulfate) with some of the metabolites associated to MetS for the first time. This metabolic signature, based solely on information extracted from the urine spectrum, adds a molecular dimension to MetS definition and it was used to generate models that can identify subjects with MetS (AUROC values between 0.86 and 0.92). This signature is particularly suitable to add meaning to the conditions that are in the interface between healthy subjects and MetS patients. Aging and non-alcoholic fatty liver disease are also risk factors that may enhance MetS probability, but they do not directly interfere with the metabolic discrimination of the syndrome.CONCLUSIONS. Urine metabolomics, studied by NMR spectroscopy, unravelled a set of metabolites that concomitantly evolve with MetS progression, that were used to derive and validate a molecular definition of MetS and to discriminate the conditions that are in the interface between healthy individuals and the metabolic syndrome.

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¹H NMR-Based Urine Metabolomics Reveals Signs of Enhanced Carbon and Nitrogen Recycling in Prostate Cancer

Cited by 25 publications

References 33 publications

Abnormal concentration of porphyrins in serum from COVID‐19 patients

Abnormal concentration of porphyrins in serum from COVID‐19 patients

Metabolic Profiling of Praziquantel-mediated Prevention ofOpisthorchis viverrini-induced Cholangiocyte Transformation in the Hamster Model of Cholangiocarcinoma

A molecular signature for the Metabolic Syndrome by urine metabolomics

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1H NMR-Based Urine Metabolomics Reveals Signs of Enhanced Carbon and Nitrogen Recycling in Prostate Cancer

Cited by 25 publications

References 33 publications

Abnormal concentration of porphyrins in serum from COVID‐19 patients

Abnormal concentration of porphyrins in serum from COVID‐19 patients

Metabolic Profiling of Praziquantel-mediated Prevention ofOpisthorchis viverrini-induced Cholangiocyte Transformation in the Hamster Model of Cholangiocarcinoma

A molecular signature for the Metabolic Syndrome by urine metabolomics

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¹H NMR-Based Urine Metabolomics Reveals Signs of Enhanced Carbon and Nitrogen Recycling in Prostate Cancer