Oxidative stress, aging, and short peptides

This article reviews oxidative stress as one of the mechanisms impairing the functions of cells, organs, and tissues. Aging is associated with reductions in the activities of the enzymes of the antioxidant system. Reactive oxygen species formed in oxidant stress damage DNA, RNA, proteins, and lipids, leading to cell apoptosi

Sirtuins: role in the regulation of oxidative stress and the pathogenesis of neurodegenerative diseases

Sirtuins (SIRTs) are a family of histone deacetylases which epigenetically regulate major cell functions. This review analyzes the role of SIRTs in controlling oxidation-reduction reactions in cells in stress. Oxidative stress and mitochondrial dysfunction are among the causes of the development of neurodegenerative pathologies-Alzheimer’s disease and Parkinson’s diseas

Influence of AEDG and KE peptides on mitochondrial staining and the expression of ribosomal protein l7a with aging of the human pineal gland and thymus cell In vitro

New molecular targets for the geroprotective activity of AEDG (epitalon) and KE (vilon) peptides were verified via confocal laser scanning microscopy. It was shown that the aging of pineal and thymic cells in vitro led to a decrease in the staining of MitoTracker Red mitochondria and that there is a compensatory increase in the synthesis of L7A ribosomal protei

Methodical organisation of teaching process in special medical groups

Современная специфика учебного труда прямым образом воздействует на функциональное состояние и психофизическую подготовленность учащейся молодежи, на что указывает рост заболеваний опорно-двигательного аппарата и нарушения вегетативной нервной системы. Предлагаемая образовательная технология направлена на профилактику данных патологий, должным образом направлена на поиск и создание условий для раскрытия, реализации и развития личностного потенциала обучающегосяModern specific academic work directly affects the functional status and psychophysical fitness of students, as indicated by the increase in locomotor apparatus and autonomic nervous system disorders. The proposed educational technology aimed at preventing these pathologies, properly focused on finding and creating the conditions for disclosure, implementation and development of individual potential studen

Sirtuins expression in the hippocampus and buccal epithelium of elderly and senile individuals with Alzheimer’s disease

Sirtuins (SIRT) are a class of NAD-dependent proteins with deacetylase activity that are involved in the regulation of transcription, metabolic pathways, and cell aging via the deacetylation of histone and nonhistone targets. It was hypothesized that sirtuins play important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s diseas

Sirtuins and chemokines as markers of replicative and induced senescence of human endotheliocytes

Background. One of the factors of the pathogenesis of atherosclerosis and other cardiovascular diseases is induced endothelial senescence. In this regard, the urgent task of molecular biology and medicine is the search for molecules that affect the process of vascular endotheliocytes senescence.The aim. To assess the expression of Sirt-1,3,6 and chemokines IL-4, CXCL11 in the replicative and induced senescence of human endotheliocytes.Materials and methods. The study was conducted on the primary culture of isolated human umbilical vein endothelial cells (HUVECs). HUVECs were cultured under conditions of replicative (natural) and lipopolysaccharide induced senescence.Results. The synthesis of Sirt-1,3,6, IL-4 and CXCL11 was evaluated using western blot analysis. We revealed a decrease in Sirt-1,3,6 synthesis by 1.6–1.8 times (р < 0.05) in the conditions of HUVEC replicative senescence. Induced senescence of endotheliocytes is characterized by a more pronounced decrease (1.7–3.4 times; р < 0.05) in the Sirt-1,3,6 synthesis. CXCL11 synthesis increases by 1.4 times (р < 0.05) in replicative and by 3.4 times (р < 0.05) in induced HUVEC senescence. IL-4 synthesis increases by 4.7 times in conditions of induced HUVEC senescence and doesn’t have changes in replicative senescence of endotheliocytes.Conclusion. These data obtained indicate that sirtuins and chemokines play an important role in the development of endothelial dysfunction observed in natural and induced senescence

Toxicity Associated with Immune Checkpoint Inhibitors: Analysis of Immune-Related Adverse Events with a Pembrolizumab Biosimilar (Pembroria)

In recent years, there has been a significant increase in the number of patients with malignancies treated with immune checkpoint inhibitors (ICIs), including the anti-programmed cell death protein 1 (anti–PD-1) agent pembrolizumab. One of the important aspects of conducting clinical trials with ICIs is the assessment of the risk of developing immune-related adverse events (irAEs).The aim of the study was to evaluate the safety of a pembrolizumab biosimilar (BCD-201, Pembroria) compared with a reference medicinal product using the results of a phase I clinical trial and the available medical literature.Materials and methods. A phase I double-blind, randomised, controlled clinical trial (BCD-201-1) has been conducted in patients with advanced melanoma and non-small-cell lung cancer (n=131). Patients were randomly allocated in a 1:1 ratio to receive either BCD-201 (Pembroria) or the reference medicinal product (Keytruda®), administered intravenously at a dose of 200 mg every 3 weeks for up to 24 weeks or until disease progression or unacceptable toxicity is observed. Since the trial results remain blinded at the time of this writing, treatment group data are masked.Results. The study demonstrated the equivalence of pharmacokinetics and comparable safety profiles of pembrolizumab biosimilar and reference medicinal products. Both medicinal products were well tolerated; the frequency of all-grade irAEs was comparable between treatment groups (21.2% in Group 1 vs 21.5% in Group 2). Most irAEs were mild to moderate, with the exception of a case of Grade 3 diarrhoea and immune-mediated enterocolitis in one study subject; there were no statistically significant differences in the median time to development of irAEs between treatment groups (Р=0.22, two-sided Wilcoxon test).Conclusions. The analysed period of the BCD-201-1 trial demonstrated comparable safety characteristics of Pembroria and Keytruda®, which is consistent with the published safety data on the latter. Information on the similarity of long-term safety profiles of the pembrolizumab biosimilar and the reference medicinal product will be obtained from ongoing clinical trials

Levilimab clinical efficacy for interleukin-6 receptor inhibition in COVID-19 and its potential for treating cytokine release syndrome of other aetiologies

The COVID-19 mortality is associated with an increase in interleukin-6 (IL-6) levels. Levilimab is an anti–IL-6 receptor antibody with proven clinical efficacy in patients with severe COVID-19.The aim of the study was to assess the association of COVID-19 severity and levilimab effectiveness with IL-6 levels and to explore the potential for using levilimab in other conditions accompanied by cytokine release syndrome.Materials and methods: the subgroup analysis was based on the data of COVID patients with known baseline IL-6 levels from the CORONA clinical study. Subgroups were formed according to baseline IL-6 levels: ≤5 pg/mL (normal) and >5 pg/mL (elevated). The subgroup analysis included descriptive statistics of the patients and time courses of their clinical and laboratory findings (at screening, on the day of investigational product administration, and further until day 14). In order to compare the percentages of patients who had required rescue therapy, the authors used Fisher's exact test.Results: the subgroup analysis included 91 patients (47 from the levilimab group and 44 from the placebo group). At baseline, the authors observed elevated levels of IL-6 in 31/47 (66%) subjects in the levilimab group and 29/44 (48.4%) subjects in the placebo group. The subjects with elevated IL-6 demonstrated more pronounced clinical signs of pneumonia and abnormalities in inflammatory markers. Elevated baseline IL-6 levels were associated with the need for rescue therapy (OR=3.714; 95% CI: 1.317–9.747; p=0.0183); this association was stronger in the placebo group (OR=8.889; 95% CI: 2.098–33.31; p=0.0036). Also, the placebo group showed long-term abnormalities in the clinical and laboratory findings.Conclusions: IL-6 is one of the key elements in the pathogenesis of cytokine release syndrome related to COVID-19 and other conditions. Elevated IL-6 levels are associated with the severity of COVID-19. Inhibition of IL-6 receptors by levilimab leads to clinical improvement in patients with severe COVID-19, suggesting the effectiveness of levilimab in pathogenesis-oriented therapy for cytokine release syndrome of other aetiologies