👤 E Yu Vasilieva

Aim    To develop of a protein panel to identify patients with progressive chronic heart failure with reduced left ventricular ejection fraction (HFrEF) based on proteomic analysis of blood fractions.Material and methods    The study included 81 patients with HFrEF associated with postinfarction myocardial scarring or dilated cardiomyopathy. Patients were enrolled both in a stable period (n=48) and with signs of decompensated heart failure (n=33). Proteomic chromatography-mass-spectrometric analysis of blood plasma and extracellular vesicles (EVs) was performed in all patients. The analysis identified proteins differentially represented between groups in each blood compartment. The effectiveness of using individual proteins and integrated protein panels based on these proteins to identify patients with progressive HFrEF was assessed.Results    Twelve plasma proteins and one BB fraction protein were detected, the concentration of which significantly differed between the groups with and without decompensated HFrEF. Individual protein concentrations demonstrated approximately the same quality indicators in identifying patients with decompensated HF as the classical HF marker, the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). Accordingly, we developed two integrated panels including the concentrations of NT-proBNP and several plasma or BB fraction proteins. The plasma panel included five proteins (APOE, LPA, C7, GPLD1, and TF), and the BB panel included two proteins (APOC4, FGB); the proteins are designated in accordance with their genes in the UniProt database. The plasma protein panel demonstrated the highest efficiency in identifying patients with decompensated HF, with a sensitivity of 78.8% and a specificity of 87.5%.Conclusion    The study resulted in the development of a plasma protein panel that can identify patients with progressive chronic HFrEF. This panel is more effective than previously described or currently used biomarkers. However, further research is needed to implement this protein panel into clinical practice. Show less

Insomnia and depression are severe sequelae of COVID-19 and often occur simultaneously. Our study examined associations of insomnia and/or depression with cognitive impairments, white matter changes, and serum biomarkers. In total, 76 long COVID patients and 22 healthy controls were examined using neuropsychiatric (ISI, HADS, and HDRS) and cognitive (MoCA, Stroop, WMT, and TMT) tests, with their blood biomarkers (anti-SARS-CoV-2, BDNF, anti-S100, anti-MBP, and anti-PLP) investigated, and underwent MRI using macromolecular proton fraction (MPF) mapping to quantify myelination. The Insomnia (n = 14), Depression (n = 12), InsDep (comorbid insomnia-depression, n = 13), and PostCovid (long COVID without depression and insomnia, n = 32) groups were identified based on psychiatric/neurological diagnoses and neuropsychiatric assessment. Cognitive performance was most affected in the Insomnia group in the MoCA and CW Stroop tests. The Depression group underperformed in the TMT and W Stroop task; the InsDep group underperformed in the WMT. The Insomnia group showed the greatest demyelination, affecting commissural (CC and tapetum), projection (CR, IC, CST, cerebral peduncles, CP, and ML), and some association pathways (SLF, SFOF), as well as most juxtacortical regions, the thalamus, and the midbrain; these changes correlated with insomnia severity. The Depression and InsDep groups showed smaller but significant overall demyelination correlated with depression severity. The Depression group exhibited the highest MPF decrease in the globus pallidus, putamen, and external capsule, while the InsDep group demonstrated the highest demyelination of the association pathways IFOF, UF, and cingulum. The anti-PLP levels were the highest in the Insomnia group and correlated with both the persistence of insomnia/depression symptoms and demyelination. Demyelination in long COVID is associated with high levels of myelin-specific autoantibodies, but symptoms of insomnia and/or depression are associated with demyelination of a different set of brain structures. Show less

G-protein-coupled receptors (GPCRs) have emerged as critical regulators of bone development and remodeling. In this study, we aimed to identify specific GPCR mutations in osteoporotic patients via next-generation sequencing (NGS). We performed NGS sequencing of six genomic DNA samples taken from osteoporotic patients and two genomic DNA samples from healthy donors. Next, we searched for single-nucleotide polymorphisms (SNPs) in GPCR genes that are associated with osteoporosis. For three osteoporotic patients and one healthy donor, bone biopsies were used to generate patient-specific mesenchymal stem cell (MSC) lines, and their ability to undergo osteodifferentiation was analyzed. We found that MSCs derived from osteoporotic patients have a different response to osteoinductive factors and impaired osteogenic differentiation using qPCR and histochemical staining assays. The NGS analysis revealed specific combinations of SNPs in GPCR genes in these patients, where SNPs in Show less

Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties. The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones. Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities. The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease. Show less

Hypercytokinemia, found in SARS-CoV-2 infection, contributes to multiple organ dysfunctions with acute respiratory distress syndrome, shock etc. The aim of this study was to describe cytokine storm signatures in patients with acute COVID-19 and to investigate their influence on severity of the infection. Plasma levels of 47 cytokines were investigated in 73 patients with moderate and severe COVID-19 (41 and 32, respectively) and 11 healthy donors (HD). The most elevated levels comparing patients and the HD were observed for seven pro-inflammatory cytokines (IL-6, IL-8, IL-15, IL-18, IL-27, IFNγ, TNFα), three chemokines (GROα, IP-10, MIG), two anti-inflammatory cytokines (IL-1RA, IL-10), and two growth factors (G-CSF, M-CSF). The patients with severe disease had significantly higher levels of FGF-2/FGF-basic, IL-1β, and IL-7 compared to the HD. The two groups of patients differed from each other only based on the levels of EGF, eotaxin, and IL-12 p40. Pneumonia lung injury, characterized by computer tomography, positively correlated with levels of EGF, IP-10, MCP-3 levels and negatively with IL-12 p40. Pro-inflammatory factors including IL-6, TNFα, and IP-10 negatively correlated with the frequency of the circulating T-helper17-like cells (Th17-like) and follicular Th cells that are crucial to develop SARS-CoV-2-specific plasma cells and memory B cells. Obtained data on the cytokine levels illustrate their influence on progression and severity of COVID-19. Show less