Amino Acid and Acylcarnitine Levels in Chronic Patients with Schizophrenia: A Preliminary Study.

Amino acids and acylcarnitines play an important role as substrates and intermediate products in most of pathways involved in schizophrenia development such as mitochondrial dysfunction, inflammation, lipid oxidation, DNA damage, oxidative stress, and apoptosis. It seems relevant to use an integrated approach with 'omics' technology to study their contribution. The aim of our study was to investigate serum amino acid and acylcarnitine levels in antipsychotics-treated patients with chronic schizophrenia compared with healthy donors. We measured serum levels of 15 amino acids and 30 acylcarnitines in 37 patients with schizophrenia and 36 healthy donors by means of tandem mass spectrometry. In summary, patients with chronic schizophrenia had an altered concentration of a few amino acids and acylcarnitines in comparison to the healthy probands. Further research is needed to assess and understand the identified changes.

Changes in Amino Acid and Acylcarnitine Plasma Profiles for Distinguishing Patients with Multiple Sclerosis from Healthy Controls.

McDonald criteria and magnetic resonance imaging (MRI) are used for the diagnosis of multiple sclerosis (MS); nevertheless, it takes a considerable amount of time to make a clinical decision. Amino acid and fatty acid metabolic pathways are disturbed in MS, and this information could be useful for diagnosis. The aim of our study was to find changes in amino acid and acylcarnitine plasma profiles for distinguishing patients with multiple sclerosis from healthy controls. We have applied a targeted metabolomics approach based on tandem mass-spectrometric analysis of amino acids and acylcarnitines in dried plasma spots followed by multivariate statistical analysis for discovery of differences between MS (n = 16) and control (n = 12) groups. It was found that partial least square discriminant analysis yielded better group classification as compared to principal component linear discriminant analysis and the random forest algorithm. All the three models detected noticeable changes in the amino acid and acylcarnitine profiles in the MS group relative to the control group. Our results hold promise for further development of the clinical decision support system.

Targeted metabolomics approach for identification of relapsing-remitting multiple sclerosis markers and evaluation of diagnostic models.

Multiple sclerosis (MS) is an inflammatory autoimmune disease that causes demyelination of nerve cell axons. This paper is devoted to the study of relapsing-remitting multiple sclerosis (RRMS) biomarkers using an LC-MS/MS-based targeted metabolomics approach and the assessment of changes in the profile of 13 amino acids and 29 acylcarnitines in plasma during the relapse of the disease. A significant increase (p < 0.05) in the concentration of glutamate in plasma in patients with RRMS was detected, while the sum of leucine and isoleucine was reduced. A decrease in the concentration of decenoylcarnitine (C10:1, p < 0.05) was observed among acylcarnitines, and this metabolite was detected as a biomarker for the disease for the first time. Several models based on a single marker or multiple pre-selected markers and multivariate analysis with a dimension reduction technique were compared in their effectiveness for the classification of RRMS and healthy controls. The best results for cross-validation showed models of general linear regression (GLM, AUC = 0.783) and random forest model (RF, AUC = 0.769) based on pre-selected biomarkers. Validation of the models on the test set showed that the RF model based on selected metabolites was the most effective (AUC = 0.72). The results obtained are promising for further development of the system of clinical decision support for the diagnosis of RRMS based on metabolic data.

Nucleotide Modifications Decrease Innate Immune Response Induced by Synthetic Analogs of snRNAs and snoRNAs.

Short nuclear regulatory RNAs play a key role in the main stages of maturation of the precursors of the major RNA species. Small nuclear RNAs (snRNAs) form the core of the spliceosome and are responsible for the splicing of pre-mRNA molecules. Small nucleolar RNAs (snoRNAs) direct post-transcriptional modification of pre-rRNAs. A promising strategy for the development of non-coding RNA (ncRNAs) mimicking molecules is the introduction of modified nucleotides, which are normally present in natural ncRNAs, into the structure of synthetic RNAs. We have created a set of snoRNAs and snRNA analogs and studied the effect of base modifications, specifically, pseudouridine (Ψ) and 5-methylcytidine (m5C), on the immune-stimulating and cytotoxic properties of these RNAs. Here, we performed a whole-transcriptome study of the influence of synthetic snoRNA analogs with various modifications on gene expression in human cells. Moreover, we confirmed the role of PKR in the recognition of snoRNA and snRNA analogs using the short hairpin RNA (shRNA) technique. We believe that the data obtained will contribute to the understanding of the role of nucleotide modification in ncRNA functions, and can be useful for creating the agents for gene regulation based on the structure of natural snoRNAs and snRNAs.

A protective chimeric antibody to tick-borne encephalitis virus.

The efficiency of several mouse monoclonal antibodies (mAbs) specific to the tick-borne encephalitis virus (TBEV) glycoprotein E in post-exposure prophylaxis was assessed, and mAb14D5 was shown to be the most active of all those studied. It was proven that the hybridoma cell line 14D5 produced one immunoglobulin H chain and two L chains. They were used to construct chimeric antibodies ch14D5a and ch14D5b, the affinity constants of which were 2.6 × 10(10)M(-1) and 1.0 × 10(7)M(-1), respectively, according to the SPR-based ProteOn biosensor assay. The neutralization index (IC50) of ch14D5a was 0.04 µg/ml in the focus reduction neutralization test. In in vivo experiments, ch14D5a at a dose of 10 µg/mouse resulted in a 100% survival of the mice infected with 240 LD50 of TBEV. This chimeric antibody is promising for further development of prevention and therapeutic drugs against TBEV.

Effect of complexation with arabinogalactan on pharmacokinetics of "guest" drugs in rats: for example, warfarin.

A pharmacokinetic study of the warfarin (WF) : arabinogalactan (AG) complex with the 1 : 10 mass ratio after its intragastric introduction to Wistar rats at a dose of 5 mg/kg (WF dose in the complex was 0.5 mg/kg) once a day for three days was conducted. It was found that Cmax, T1/2, and AUC of WF in the complex form were lower than after the introduction of blank WF at the same dose, but its elimination (Cl, MRT) was much faster. Significant accumulation (C(min)) and an abrupt increase in plasma concentration after the third introduction were observed for blank WF, whereas the complex showed a much more moderate increase in concentration at this point. However, despite obvious differences in pharmacokinetic parameters, the efficacies of both agents were virtually identical; the complex differed from blank WF by only 15%. This value is rather insignificant and does not impair its anticoagulant activity. Thus, we can conclude that introduction of the WF : AG complex is safe in terms of reduction of the bleeding risk and accumulation.