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Ł. Boguszewicz A. Hajduk J. Mrochem-Kwarciak A. Skorupa M. Ciszek A. Heyda K. Składowski M. Sokół 《Metabolomics : Official journal of the Metabolomic Society》2016,12(6):102
Introduction
Anticancer treatment results in temporary or permanent toxicity considered as changes in normal tissues and/or involved regions. The net effect is mirrored in morphological, functional and molecular disturbances—thus in a systemic response of the human body. To date, specific NMR biomarkers of radiation therapy toxicity in head and neck squamous cell carcinoma (HNSCC) patients are scarce or even missing.Objectives
We aimed to investigate molecular processes reflecting acute radiation sequelae (ARS) in HNSCC patients using NMR-based metabolomics of blood serum.Methods
45 patients with HNSCC were treated with radiotherapy (RT) or chemoradiotherapy (CHRT). Blood samples were collected within a week after RT/CHRT completion. Patients were divided into two classes (of high and low ARS) on the basis of the highest individual ARS value observed during the treatment. 1H NMR spectra of serum samples were acquired on a Bruker 400.13 MHz spectrometer at 310 K and analyzed using principal component analysis and orthogonal partial least squares discriminant analysis. Additional statistical analyses were performed on quantified metabolites.Results
1D projections of the J-resolved NMR spectra seem to be of the great potential in the quest for the HNSCC treatment toxicity biomarker. The metabolic features characteristic for high ARS are the increased signals of N-acetyl-glycoprotein and acetate, as well as decrease of choline and the metabolites involved in energy metabolism: branched chain amino acids (BCAAs), alanine, creatinine and carnitine. Furthermore, we observed significant correlations between N-acetyl-glycoprotein and clinical markers of inflammation as well as acetate and a percentage-weight-loss during the treatment. CRP was also negatively correlated with alanine and BCAAs.Conclusion
NMR-based metabolomics provides relevant biomarkers of RT/CHRT toxicity (ARS) in HNSCC patients. The results indicate at least three concomitant processes related to high ARS: inflammation, altered energy metabolism and disturbed membrane metabolism, and indicate an exciting potential of J-resolved NMR spectroscopy combined with multivariate projection techniques.3.
Agnieszka Skorupa Łukasz Boguszewicz Marek Kijonka Maria Sokół 《Metabolomics : Official journal of the Metabolomic Society》2017,13(4):34
Introduction
In recent years multivariate projection techniques of data analysis (PCA, PLS-DA) have been increasingly used for detection of complex 1H MRS derived metabolic signatures in pathologic conditions. However, these techniques have not been applied in the studies of metabolic heterogeneity of the normal human brain.Objective
In this work we extended current knowledge about regional distribution of metabolites by multivariate analysis of metabolite levels obtained from various cortical and subcortical regions.Methods
The studied group consisted of 71 volunteers with no neurological disorders. The metabolite levels obtained from short echo time 1H MRS in vivo spectra were subjected to univariate and multivariate analysis.Results
The major variance direction in the dataset was dominated by glutamine?+?glutamate, creatine, myo-inositol and was successful in differentiation of the cortical grey matter and cerebellar vermis from the cortical white matter, pons, basal ganglia, hippocampus and thalamus. The projection plane formed by the second and third variance directions was dominated by N-acetylaspartate?+?N-acetylaspartylglutamate, choline and glutamine?+?glutamate variation not explained by the first direction. This plane revealed a huge metabolic contrast between the pons and basal ganglia, differentiation between the cortical grey matter regions and cerebellar vermis as well as biochemical heterogeneity between the regions such as: thalamus, basal ganglia and hippocampus.Conclusion
Multivariate approach to 1H MRS data analysis provides an insight into the normal brain biochemistry and is helpful in understanding the regional heterogeneity of the normal brain. Such knowledge is crucial for a proper interpretation of altered metabolic pathways in diseases.4.
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Angiotensin II (1 microgram) dissolved in water and given intracerebroventricularly on day 1, 15 min before the first learning session, enhanced rate of learning of active avoidance in rats over the next 7 days. However, the peptide, dissolved in 0.25 M NaCl, and given at the same dose and route, stimulated learning significantly more than that dissolved in water. A possible involvement of Na+ ions in facilitating learning action of A II is discussed. 相似文献
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