👤 Alexandr A Nikolsky

Kidney diseases pose a serious healthcare problem because of their high prevalence, worsening of patients' quality of life, and high mortality. Patients with kidney diseases are often asymptomatic until disease progression starts. Expensive renal replacement therapy options, such as dialysis or kidney transplant, are required for end-stage kidney disease. Early diagnosis of kidney pathology is crucial for slowing down or curbing further damage. This study aimed to analyze the features of the protein composition of blood plasma in patients with the most common kidney pathologies: kidney calculus, kidney cyst, and kidney cancer. The study involved 75 subjects. Proteins associated with kidney pathologies (CFB, SERPINA3, HPX, HRG, SERPING1, HBB, ORM2, and CP) were proposed. These proteins are important participants of complement and coagulation cascade activation and lipid metabolism. The revealed phosphorylated proteoforms (CFB, C4A/C4B, F2, APOB, TTR, and NRAP) were identified. For them, modification sites were mapped on 3D protein models, and the potential role in formation of complexes with native partner proteins was assessed. The study demonstrates that the selected kidney pathologies have a similar proteomic profile, and patients can be classified into kidney pathology groups with an accuracy of (70-80)%. Show less

Respiratory syncytial virus (RSV) causes severe pathology of the lower respiratory tract in infants, immunocompromised people, and elderly. Despite decades of research, there is no licensed vaccine against RSV, and many therapeutic drugs are still under development. Detailed understanding of molecular and cellular mechanisms of the RSV infection pathology can accelerate the development of efficacious treatment. Current studies on the RSV pathogenesis are based on the analysis of biopsies from the infected patients; however deeper understanding of molecular and cellular mechanisms of the RSV pathology could be achieved using animal models. Mice are the most often used model for RSV infection because they exhibit manifestations similar to those observed in humans (bronchial obstruction, mucous hypersecretion, and pulmonary inflammation mediated by lymphocytes, macrophages, and neutrophils). Additionally, the use of mice is economically feasible, and many molecular tools are available for studying RSV infection pathogenesis at the molecular and cellular levels. This review summarizes new data on the pathogenesis of RSV infection obtained in mouse models, which demonstrated the role of T cells in both the antiviral defense and the development of lung immunopathology. T cells not only eliminate the infected cells, but also produce significant amounts of the proinflammatory cytokines TNFα and IFNγ. Recently, a new subset of tissue-resident memory T cells (TRM) was identified that provide a strong antiviral defense without induction of lung immunopathology. These cells accumulate in the lungs after local rather than systemic administration of RSV antigens, which suggests new approaches to vaccination. The studies in mouse models have revealed a minor role of interferons in the anti-RSV protection, as RSV possesses mechanisms to escape the antiviral action of type I and III interferons, which may explain the low efficacy of interferon-containing drugs. Using knockout mice, a significant breakthrough has been achieved in understanding the role of many pro-inflammatory cytokines in lung immunopathology. It was found that in addition to TNFα and IFNγ, the cytokines IL-4, IL-5, IL-13, IL-17A, IL-33, and TSLP mediate the major manifestations of the RSV pathogenesis, such as bronchial obstruction, mucus hyperproduction, and lung infiltration by pro-inflammatory cells, while IL-6, IL-10, and IL-27 exhibit the anti-inflammatory effect. Despite significant differences between the mouse and human immune systems, mouse models have made a significant contribution to the understanding of molecular and cellular mechanisms of the pathology of human RSV infection. Show less