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Classifying heart failure (HF) by stages and ejection fraction (EF) remains a debated topic in cardiology. Metabolomic profiling (MP) offers a means to identify unique pathophysiological changes across different phenotypes, presenting a promising approach for the diagnosis and prognosis of HF, as well as for the development of targeted therapies. In our study, MP was performed on 408 HF patients (54.9% male). The mean ages of patients were 62 [53;68], 67 [65;74], 68 [61;72], and 69 [65;73] years for stages A, B, C, and D, respectively. This study demonstrates high accuracy in HF stage classification, distinguishing Stage A from Stage B with an AUC ROC of 0.91 and Stage B from Stage C with an AUC ROC of 0.97, by integrating chromatography-mass spectrometry data through multiparametric machine learning models. The observed metabolic similarities between HF with mildly reduced EF and HF with reduced EF phenotypes (AUC ROC 0.96) once again highlight the fundamental differences at the cellular and molecular levels between HF with preserved EF and HF with EF < 50%. Hierarchical clustering based on MP identified four distinct HF phenotypes and 26 key metabolites, including metabolites of tryptophan catabolism, glutamine, riboflavin, norepinephrine, serine, and long- and medium-chain acylcarnitines. The average follow-up period was 542.37 [16;1271] days. A downward change in the trajectory of EF [HR 3,008, 95% CI 1,035 to 8,743, p  = 0,043] and metabolomic cluster 3 [HR 2,880; 95% CI 1,062 to 7,810, p  = 0,0376] were associated with increased risk of all-cause mortality. MP can refine HF phenotyping and deepen the understanding of its underlying mechanisms. Metabolomic analysis illuminates the biochemical landscape of HF, aiding in its classification and suggesting new therapeutic pathways.

Prostanit is a novel drug developed for the treatment of peripheral arterial diseases. It consists of a prostaglandin E1 (PGE1) moiety with two nitric oxide (NO) donor fragments, which provide a combined vasodilation effect on smooth muscles and vascular spastic reaction. Prostanit pharmacokinetics, however, remains poorly investigated. Thus, the object of this study was to investigate the pharmacokinetics of Prostanit-related and -affected metabolites in rabbit plasma using the liquid chromatography-mass spectrometry (LC-MS) approach. Besides, NO generation from Prostanit in isolated rat aorta and human smooth muscle cells was studied using the Griess method. In plasma, Prostanit was rapidly metabolized to 1,3-dinitroglycerol (1,3-DNG), PGE1, and 13,14-dihydro-15-keto-PGE1. Simultaneously, the constant growth of amino acid (proline, 4-hydroxyproline, alanine, phenylalanine, etc.), steroid (androsterone and corticosterone), and purine (adenosine, adenosine-5 monophosphate, and guanosine) levels was observed. Glycine, aspartate, cortisol, and testosterone levels were decreased. Ex vivo Prostanit induced both NO synthase-dependent and -independent NO generation. The observed pharmacokinetic properties suggested some novel beneficial activities (i.e., effect prolongation and anti-inflammation). These properties may provide a basis for future research of the effectiveness and safety of Prostanit, as well as for its characterization from a clinical perspective.

Metabolomics is a promising technology for the application of translational medicine to cardiovascular risk. Here, we applied a liquid chromatography/tandem mass spectrometry approach to explore the associations between plasma concentrations of amino acids, methylarginines, acylcarnitines, and tryptophan catabolism metabolites and cardiometabolic risk factors in patients diagnosed with arterial hypertension (HTA) (n = 61), coronary artery disease (CAD) (n = 48), and non-cardiovascular disease (CVD) individuals (n = 27). In total, almost all significantly different acylcarnitines, amino acids, methylarginines, and intermediates of the kynurenic and indolic tryptophan conversion pathways presented increased (p < 0.05) in concentration levels during the progression of CVD, indicating an association of inflammation, mitochondrial imbalance, and oxidative stress with early stages of CVD. Additionally, the random forest algorithm was found to have the highest prediction power in multiclass and binary classification patients with CAD, HTA, and non-CVD individuals and globally between CVD and non-CVD individuals (accuracy equal to 0.80 and 0.91, respectively). Thus, the present study provided a complex approach for the risk stratification of patients with CAD, patients with HTA, and non-CVD individuals using targeted metabolomics profiling.

The influence of Eu doping (0.5, 1 and 2 mol.%) and annealing in an oxygen-deficient atmosphere on the structure and optical properties of SnO2 nanoparticles were investigated in relation to electronic structure. The X-ray diffraction (XRD) patterns revealed single-phase tetragonal rutile structure for both synthesized and annealed Eu-doped SnO2 samples, except for the annealed sample with 2 mol.% Eu. The results of X-ray photoelectron spectroscopy (XPS) emphasized that europium incorporated into the SnO2 host lattice with an oxidation state of 3+, which was accompanied by the formation of oxygen vacancies under cation substitution of tetravalent Sn. Moreover, XPS spectra showed the O/Sn ratio, which has been reduced under annealing for creating additional oxygen vacancies. The pulse cathodoluminescence (PCL) demonstrated the concentration dependence of Eu site symmetry. Combination of XRD, XPS and PCL revealed that Eu doping and following annealing induce strongly disordering of the SnO2 crystal lattice. Our findings provide new insight into the interaction of rare-earth metals (Eu) with host SnO2 matrix and new evidence for the importance of oxygen vacancies for optical and electronic structure formation.

The strong psychoactive effects of synthetic cannabinoids raise the need for the deeper studying of their neurometabolic effects. The pharmacokinetic properties of 5F-APINAC and its influence on metabolomics profiles associated with neurotransmission were investigated in rabbit plasma. Twelve rabbits divided into three groups received 1-mL 5F-APINAC at 0.1, 1 and 2 mg/kg. The intervention groups were compared with the controls. Sampling was performed at nine time points (0–24 h). Ultra-high-performance liquid chromatography–tandem mass spectrometry was used. The pharmacokinetics were dose-dependent (higher curve at a higher dose) with a rapid biotransformation, followed by gradual elimination within 24 h. The tryptophan concentrations abruptly decreased (p < 0.05) in all tested groups, returning to the basal levels after 6 h. 5-hydroxylindole acetic acid increased (p < 0.05) in the controls, but this trend was absent in the treated groups. The aspartic acid concentrations were elevated (p < 0.001) in the treated groups. L-kynurenine was elevated (p < 0.01) in the intervention groups receiving 1 mg/kg to 2 mg/kg. Dose-dependent elevations (p < 0.01) were found for kynurenic acid, xanthurenic acid and quinolinic acid (p < 0.01), whereas the anthranilic acid trends were decreased (p < 0.01). The indole-3-propionic acid and indole-3-carboxaldehyde trends were elevated (p < 0.05), whereas the indole-3-lactic acid trajectories were decreased (p < 0.01) in the intervention groups. 5F-APINAC administration had a rapid biotransformation and gradual elimination. The metabolites related to the kynurenine and serotonergic system/serotonin pathways, aspartic acid innervation system and microbial tryptophan catabolism were altered.

The influence of Eu doping (0.5, 1 and 2 mol.%) and annealing in an oxygen-deficient atmosphere on the structure and optical properties of SnO nanoparticles were investigated in relation to electronic structure. The X-ray diffraction (XRD) patterns revealed single-phase tetragonal rutile structure for both synthesized and annealed Eu-doped SnO samples, except for the annealed sample with 2 mol.% Eu. The results of X-ray photoelectron spectroscopy (XPS) emphasized that europium incorporated into the SnO host lattice with an oxidation state of 3+, which was accompanied by the formation of oxygen vacancies under cation substitution of tetravalent Sn. Moreover, XPS spectra showed the O/Sn ratio, which has been reduced under annealing for creating additional oxygen vacancies. The pulse cathodoluminescence (PCL) demonstrated the concentration dependence of Eu site symmetry. Combination of XRD, XPS and PCL revealed that Eu doping and following annealing induce strongly disordering of the SnO crystal lattice. Our findings provide new insight into the interaction of rare-earth metals (Eu) with host SnO matrix and new evidence for the importance of oxygen vacancies for optical and electronic structure formation.

The influence of Eu doping (0.5, 1 and 2 mol.%) and annealing in an oxygen-deficient atmosphere on the structure and optical properties of SnO[sub.2] nanoparticles were investigated in relation to electronic structure. The X-ray diffraction (XRD) patterns revealed single-phase tetragonal rutile structure for both synthesized and annealed Eu-doped SnO[sub.2] samples, except for the annealed sample with 2 mol.% Eu. The results of X-ray photoelectron spectroscopy (XPS) emphasized that europium incorporated into the SnO[sub.2] host lattice with an oxidation state of 3+, which was accompanied by the formation of oxygen vacancies under cation substitution of tetravalent Sn. Moreover, XPS spectra showed the O/Sn ratio, which has been reduced under annealing for creating additional oxygen vacancies. The pulse cathodoluminescence (PCL) demonstrated the concentration dependence of Eu site symmetry. Combination of XRD, XPS and PCL revealed that Eu doping and following annealing induce strongly disordering of the SnO[sub.2] crystal lattice. Our findings provide new insight into the interaction of rare-earth metals (Eu) with host SnO[sub.2] matrix and new evidence for the importance of oxygen vacancies for optical and electronic structure formation.