Publications by authors named "Alexander G Brzhozovskiy"

Background/objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue.

Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort.

Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples.

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Objectives: The COVID-19 pandemic has exposed a number of key challenges that need to be urgently addressed. Mass spectrometric studies of blood plasma proteomics provide a deep understanding of the relationship between the severe course of infection and activation of specific pathophysiological pathways. Analysis of plasma proteins in whole blood may also be relevant for the pandemic as it requires minimal sample preparation.

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The study of urinary peptidome is an important area of research, which concerns the characterization of endogenous peptides, as well as the identification of biomarkers for a wide range of socially significant diseases. First of all, this relates to renal and genitourinary pathologies and/or pathologies associated with proteinuria, such as kidney diseases, bladder, prostate and ovarian cancers, diabetic nephropathy, and pre-eclampsia. Unlike proteins, peptides do not require proteolytic hydrolysis, can be analyzed in their native form and can provide certain information about occurring (patho)physiological processes.

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Intrauterine growth restriction (IUGR) remains a significant concern in modern obstetrics, linked to high neonatal health problems and even death, as well as childhood disability, affecting adult quality of life. The role of maternal and fetus adaptation during adverse pregnancy is still not completely understood. This study aimed to investigate the disturbance in biological processes associated with isolated IUGR via blood plasma proteomics.

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Metastasis is a serious and often life-threatening condition, representing the leading cause of death among women with breast cancer (BC). Although the current clinical classification of BC is well-established, the addition of minimally invasive laboratory tests based on peripheral blood biomarkers that reflect pathological changes in the body is of utmost importance. In the current study, the serum proteome and lipidome profiles for 50 BC patients with (25) and without (25) metastasis were studied.

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Glomerulopathies with nephrotic syndrome that are resistant to therapy often progress to end-stage chronic kidney disease (CKD) and require timely and accurate diagnosis. Targeted quantitative urine proteome analysis by mass spectrometry (MS) with multiple-reaction monitoring (MRM) is a promising tool for early CKD diagnostics that could replace the invasive biopsy procedure. However, there are few studies regarding the development of highly multiplexed MRM assays for urine proteome analysis, and the two MRM assays for urine proteomics described so far demonstrate very low consistency.

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Article Synopsis
  • Primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are kidney disorders characterized by damage to podocytes, leading to nephrotic syndrome, but their underlying causes remain unclear.
  • A study was conducted to analyze the urinary proteomic profiles of patients with FSGS and MCD, involving 30 FSGS and 9 MCD patients, who were categorized based on disease severity using a scoring system.
  • The results identified 22 proteins with significant differences between severe and mild cases of FSGS and MCD, with consistent patterns observed in both initial and targeted analyses, suggesting distinct proteomic signatures for each condition.
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Early recognition of the risk of Alzheimer's disease (AD) onset is a global challenge that requires the development of reliable and affordable screening methods for wide-scale application. Proteomic studies of blood plasma are of particular relevance; however, the currently proposed differentiating markers are poorly consistent. The targeted quantitative multiple reaction monitoring (MRM) assay of the reported candidate biomarkers (CBs) can contribute to the creation of a consistent marker panel.

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Changes in bacterial physiology caused by the combined action of the magnetic force and microgravity were studied in grown using a specially developed device aboard the International Space Station. The morphology and metabolism of grown under spaceflight (SF) or combined spaceflight and magnetic force (SF + MF) conditions were compared with ground cultivated bacteria grown under standard (control) or magnetic force (MF) conditions. SF, SF + MF, and MF conditions provided the up-regulation of Ag43 auto-transporter and cell auto-aggregation.

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Article Synopsis
  • Alzheimer's disease (AD) is primarily caused by the buildup of β-amyloid (Aβ) peptide, which forms plaques in the brains of the elderly, contributing to dementia.
  • * Recent research tracked the accumulation of specific Aβ proteoforms, particularly isoD7-Aβ, in a widely used mouse model (5xFAD) over time using advanced mass spectrometry techniques.
  • * Findings showed that the fraction of isoD7-Aβ in these mice increased significantly with age, suggesting a potential link between this specific proteoform and the progression of AD.
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Despite the differences in the clinical manifestations of major obstetric syndromes, such as preeclampsia (PE) and intrauterine growth restriction (IUGR), their pathogenesis is based on the dysregulation of proliferation, differentiation, and invasion of cytotrophoblast cells that occur in the developing placenta, decidual endometrium, and myometrial parts of the spiral arteries. To understand the similarities and differences in the molecular mechanisms of PE and IUGR, samples of the placental bed and placental tissue were analyzed using protein mass spectrometry and the deep sequencing of small RNAs, followed by validation of the data obtained by quantitative RT-PCR in real time. A comparison of the transcriptome and proteomic profiles in the samples made it possible to conclude that the main changes in the molecular profile in IUGR occur in the placental bed, in contrast to PE, in which the majority of molecular changes occurs in the placenta.

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The detection of viral RNA by polymerase chain reaction (PCR) is currently the main diagnostic tool for COVID-19 ( 2019, 25 (3), 1). The PCR-based test, however, shows limited sensitivity, especially in the early and late stages of disease development ( 2020, 581, 465-469; 2020, 119 (6) 1123), and is relatively time-consuming. Fast and reliable complementary methods for detecting the viral infection would be of help in the current pandemic conditions.

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Comprehensive studies of the effects of prolonged exposure to space conditions and the overload experienced during landing on physiological and biochemical changes in the human body are extremely important in the context of planning long-distance space flights, which can be associated with constant overloads and various risk factors for significant physiological changes. Exhaled breath condensate (EBC) can be considered as a valuable subject for monitoring physiological changes and is more suitable for long-term storage than traditional monitoring subjects such as blood and urine. Herein, the EBC proteome changes due to the effects of spaceflight factors are analyzed.

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Article Synopsis
  • The study compared how spaceflight and related ground-based experiments affect protein levels in the human body by analyzing blood plasma samples from cosmonauts and participants in simulated conditions.
  • Significant changes in protein levels were observed, with 19 proteins altered right after landing, 44 during head-down bed rest, and 31 in dry immersion experiments.
  • Nine common proteins across all conditions indicate shared biological processes, like platelet activation and protein metabolism, but differences in protein changes suggest varying effects between actual spaceflight and ground-based simulations.
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Cervicovaginal fluid (CVF) is a valuable source of clinical information about the female reproductive tract in both nonpregnant and pregnant women. The aim of this study is to specify the CVF proteome at different stages of cervix neoplastic transformation by label-free quantitation approach based on liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The proteome composition of CVF from 40 women of reproductive age with human papillomavirus (HPV)-associated cervix neoplastic transformation (low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], and CANCER) was investigated.

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Background: The strategy of adaptation of the human body in microgravity is largely associated with the plasticity of cardiovascular system regulatory mechanisms. During long-term space flights the changes in the stroke volume of the heart are observed, the heart rate decreases, the phase structure of cardiac cycle is readjusted The purpose of this work was to clarify urine proteome changes associated with the initial condition of the heart rate autonomic regulation mechanisms in cosmonauts who have participated in long space missions. Urine proteome of each cosmonaut was analyzed before and after space flight, depending on the initial parameters characterizing the regulatory mechanisms of the cardiovascular system.

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