[Chondrocytes secretory phenotype associated with aging: role in the pathogenesis of osteoarthritis and prospects for peptide bioregulation.]

Osteoarthritis (OA) is a socially significant age-associated disease, for the treatment of which a search for new effective drugs is underway. The development of OA correlates with the development of the aging-associated secretory chondrocyte phenotype (SASP). The purpose of the review is to analyze the pool of signaling molecules that form SASP of chondrocytes in OA and substantiate the possibility of peptide chondroprotection. It has been established that SASP of chondrocytes is characterized by a decrease in the synthesis of sirtuins, impaired remodeling of the extracellular matrix, and activation of cytokine production. Sigumir, a polypeptide complex of cartilage and bone tissues of young animals, and the AED tripeptide (Kartalax) have shown high efficacy in animal models of OA and oral administration in patients with OA of older age groups. These peptide substances regulate the synthesis of proapoptotic and proliferotropic molecules that form the SASP of chondrocytes.

[Peptides prevent the forming of secretory phenotype of chondrocytes associated with the aging.]

Secretory phenotype associated with the aging (SASP) of chondrocytes forms the conditions for the musculoskeletal system diseases development, in particular, osteoarthritis (OA). The search for effective methods for OA treating is an urgent task of molecular gerontology. The purpose of this work is to characterize the SASP of chondrocytes and to conduct a comparative assessment of the effect of AED peptide and the cartilage polypeptide complex (CPC). It was found that chondrocyte's SASP is characterized by an increase of the synthesis of p16, p21, p53 pro-apoptotic proteins, TNF-α, IL-1α pro-inflammatory cytokines and a decrease of Sirt1synthesis. Peptides AED and CPC normalize the synthesis of molecules that form SASP of chondrocytes. This effect may explain their geroprotective effect and effectiveness in studies of various pathologies of the musculoskeletal system, including OA.

[Roles of active forms of vitamin D in supporting innate immune systems and in reducing excess inflammation in COVID-19].

A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).

Comparison of the Effects of KE and AED Peptides on Functional Activity of Human Skin Fibroblasts during Their Replicative Aging.

We studied the effect of KE and AED peptides on the expression of sirtuin-1, sirtuin-6, collagen I, cytokines (IL-1, TGF-ß), and transcription factor NF-κB in human skin fibroblasts during their replicative aging. Immunocytochemical analysis and confocal microscopy showed that KE peptide reduces the synthesis of factors of the inflammatory response IL-1, NF-κB, and TGF-ß and stimulates the synthesis of sirtuin-6. KE peptide normalizes the immunological function of human skin fibroblasts during their aging. AED peptide activates the synthesis of sirtuin-1, sirtuin-6, and collagen I in human skin fibroblasts during their replicative aging, which attests to its geroprotective effect.

An Inducible DamID System for Profiling Interactions of Nuclear Lamina Protein Component Lamin B1 with Chromosomes in Mouse Cells.

At the level of DNA organization into chromatin, there are mechanisms that define gene expression profiles in specialized cell types. Genes within chromatin regions that are located at the nuclear periphery are generally expressed at lower levels; however, the nature of this phenomenon remains unclear. These parts of chromatin interact with nuclear lamina proteins like Lamin B1 and, therefore, can be identified in a given cell type by chromatin profiling of these proteins. In this study, we created and tested a Dam Identification (DamID) system induced by Cre recombinase using Lamin B1 and mouse embryonic fibroblasts. This inducible system will help to generate genome-wide profiles of chromatin proteins in given cell types and tissues with no need to dissect tissues from organs or separate cells from tissues, which is achieved by using specific regulatory DNA elements and due to the high sensitivity of the method.

[Prospects of buccal epithelium application for noninvasive diagnosis of coronary heart disease in people of different age.]

Cardiovascular diseases caused by atherosclerosis, in many countries of the world are one of the most important social and economic problems due to the high morbidity and mortality rate of the working population. Recently, the immunological theory of atherosclerosis and coronary heart disease (CHD) has been actively developed, and the search for markers of inflammation characterizing immuno- and atherogenesis has been conducted. Buccal epithelium (BE) can be used as biological material for in vivo molecular-cellular studies, allowing to diagnose CHD by inflammation markers. The purpose of the work was a comparative study of the expression of IL-1ß, IL-6, IL-10, MCP-1 and GDF-15 in BE in patients of different ages with CHD and without cardiovascular disease. The material of BE in healthy donors and patients with 2nd stage CHD was divided into groups according to age classification of the WHO: the 1st - middle-aged people (45-59 years) and the 2nd - elderly people (60-74 years). Control material was obtained from people of middle and old age without cardiovascular disease. According to the immunocytochemical study, the area of IL-1ß expression in BE is 3 times higher in middle-aged people with CHD, and in 4,4 times higher in elderly people compared to healthy individuals of the same age group. The area of IL-6 expression in middle-aged and elderly people with CHD was in 7,9 and 7,4 times higher, respectively, than in the control group. In middle-aged and elderly patients with CHD, IL-10 expression was in 1,6 and 2,8 times higher, respectively, compared to healthy donors of the same age group. The expression of MCP-1 in BE of middle-aged and elderly people in normal and ischemic heart disease did not differ. GDF-15 expression is in 6,8 and 6,6 times higher in middle-aged and elderly people with CHD than in healthy people of the same age. The findings showed that the expression of the cytokines IL-1ß, IL-6, IL-10 and GDF-15 increase in BE in patients with CHD of middle-aged and elderly people compared with persons of the same age group without cardiovascular disease. Thus, BE can serve as an informative material for noninvasive molecular diagnosis of CHD in people of different ages.

[Molecular markers of Alzheimer disease early diagnostic: investigation perspectives of peripheral tissues.]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of elderly and old age people. For intravital diagnosis of the expression of signaling molecules - AD markers, cerebrospinal fluid (CSF) and peripheral tissues are used: lymphocytes and blood platelets, buccal and olfactory epithelium, skin fibroblasts. There are several changes in the production of hyper phosphorylated form of τ-protein, BACE1 and peptide Аß42 in CSF in case of AD, but CSF taking may have a number of side effects. Less traumatic taking of sampling tissues for the diagnosis of AD is in use of epithelium biopsy and blood portion. An increase in the expression of the hyper phosphorylated form of τ-protein is shown in blood lymphocytes of AD patients. An increase in the content of high molecular weight forms of phosphorylated t-protein and amyloid precursor protein-APP was also revealed in blood platelets of AD patients. Changes in the amount of 2 miRNA families - miR-132 family and miR-134 family were revealed in blood cells 1-5 years before the manifestation of clinical signs of AD. An increase in the concentration of bound calcium, synthesis of peptides Aß40 and Aß42, τ protein was observed in AD skin fibroblasts. In the olfactory and buccal epithelium an increase in the expression of hyper phosphorylated form of τ-protein and Aß peptide was detected in patients with AD. Verification of AD markers in peripheral tissues for biopsy have the important significant for life diagnostics, prevention and and target AD treatment.

[New strains of basidiomycetes that produce bioethanol from lignocellulose biomass].

Sixty six isolates were screened for ability of bioethanol production; dynamics of product accumulation and substrate utilization were investigated for two selected strains Trametes hirsuta MT-24.24 and Trametes versicolor IT-1. The strains' efficiency was evaluated as bioethanol production by 1 g biomass. Strain T. versicolor IT-1 producing over 33 g/L of the ethanol for 9 d was selected. Direct conversion of Na-carboxymethyl cellulose, microcrystalline cellulose and straw was shown with ethanol yields of 2.1, 1.6 and 1.7 g/L, respectively, for 9 d fermentation time.

Cross-language analysis of phonetic units in language addressed to infants.

In the early months of life, infants acquire information about the phonetic properties of their native language simply by listening to adults speak. The acoustic properties of phonetic units in language input to young infants in the United States, Russia, and Sweden were examined. In all three countries, mothers addressing their infants produced acoustically more extreme vowels than they did when addressing adults, resulting in a "stretching" of vowel space. The findings show that language input to infants provides exceptionally well-specified information about the linguistic units that form the building blocks for words.

Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites.

The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD+, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.

[Obtaining monoclonal antibodies to Bordetella pertussis antigens]. / Poluchenie monoklonal'nykh antitel k antigenam Bordetella pertussis.

The immunization of mice with the protein fraction of B. pertussis strain 305 has made it possible to obtain hybridomas producing monoclonal antibodies to B. pertussis antigens. Ascitic fluids containing monoclonal antibodies react in the ELISA in high titers and actively agglutinate B. pertussis strains 305 and 475.

[Isolation of hemolytic cultures of Bordetella pertussis intended for the production of acellular pertussis preparations and the characterization of their biological properties]. / Vydelenie gemoliticheskikh kul'tur Bordetella pertussis dlia prigotovleniia beskletochnykh kokliushnykh preparatov i kharakteristika ikh biologicheskikh svoistv.

The heterogeneity of the population of B. pertussis laboratory strains with respect to the capacity of individual clones to lyse erythrocytes has been established. The complete or partial reduction of the antigens under study in nonhemolytic bacteria has been shown. The use of hemolytic cultures for the preparation of acellular pertussis vaccine makes it possible to increase the content of B. pertussis toxin in these vaccines.

[Cultivation of murine B-cell hybridomas in the spleen]. / Kul'tivirovanie myshinykh B-kletochnykh gibridom v selezenke.

The tumorigenic capacity of mouse B-cell hybridomas in both cloned and primary cultures was studied. The cells were selected for inoculation from 24-well plates and introduced into the spleen of syngeneic mice. The cells took in 50% of the animals. The cells of hybridoma tumors induced as the result of intrasplenic inoculation, when subcultured in the second passage following the standard scheme, i.e. inoculated intraperitoneally in a dose of 1 X 10(7) cells into mice previously treated with vaseline oil or pristane, produced tumors in 100% of the animals.

[Natural classification of acoustic stimuli with different amplitude jump delay times]. / Estestvennaia klassifikatsiia zvukovykh stimulov s raznym vremenem otstavleniia skachka ogibaiushchei.

Natural categorization of stimuli with different delay of amplitude jump was observed. No training was necessary for discrimination of stimuli with and without onset irregularity. The variance of identification functions between subjects was the same as the variance of identification functions for one subject measured in different days.

[Appreciation of approaching and departing sources of natural acoustic signals]. / Otsenka priblizheniia i udaleniia istochnika estestvennykh zvukovykh signalov.

Perception of natural sounds of approaching and moving away footsteps was studied. Footsteps are sequences of low-frequency noise bursts separated by short pauses. "Loudness" of bursts in sequences estimated as approaching steps was irregularly increasing, "loudness" in sequences estimated as moving away steps was irregularly decreasing. The irregularity did not prevent correct estimation of movement direction.

[The effect of polikatan on the ototoxic action of kanamycin]. / Vliianie polikatana na ototoksicheskoe deistvie kanamitsina.

Experiments on guinea pigs demonstrated that preliminary injection of polycatan (standardized magnesium solution containing the mineral bischofite) into the parotid region by means of electrophoresis reduces the ototoxic effect of the aminoglycoside antibiotic kanamycin. Polycatan prevents kanamycin-induced degenerative changes of the hair cells found in the labyrinth of the internal ear and improves the local blood flow.

[Carbohydrate metabolism in the kidneys of rats with dimethylnitrosamine-induced tumors]. / Uglevodnyi obmen v pochkakh krys pri opukholiakh, indutsirovannykh dimetilnitrozaminom

Under study was anaerobic glycolysis, the activity of hexokinase, lactate dehydrogenase, gluco-6-phosphatase in rat kidneys in dimethylnitrosamine (DMNA) induced tumors in them. DMNA was administered perorally in the dosage of 10 mg/Kg during 4 weeks (25 mg per rat). Following 8 months tumors developed in the renal cortical substance. The tumor tissue, the renal cortical substance adjacent to the tumor, and the renal cortical substance without macroscopic tumor signs have been studied. An increased glycolysis, hexokinase and lactatedehydrogenase activity were noted, whereas the activity of glucoso-6-phosphatase was diminished in all tissues under examination. Changes of all indices were mostly pronounced in tumor tissue and least significant--in the renal cortical layer without any macroscopic tumor signs.

[Effect of ionol on carcinogenesis in the kidneys]. / Vliianie ionola na kantserogenez v pochkakh.

The effect of treatment with an antioxidant--ionol (2,6-di-tert-butyl, 4-methylphenol)--on nitrosodimethylamine-induced carcinogenesis was studied. Large doses of ionol were found to inhibit tumor development in the kidney. This also involved intensification of spontaneous peroxidation of renal cortical membrane cell lipids which in turn was inhibited when additional stimulation with iron was carried out.

[Immune and hormonal response to dimethylnitrosamine]. / Immunnyi i gormonal'nyi otvet organizma na deistvie nitrozodimetilamina.

The study was concerned with assay of levels of 11- HOCS in blood and adrenal tissues and antibody-producing cells in the spleen as well as spontaneous rosette-formation by blood thymic and splenic lymphocytes in the course of carcinogenesis induced in experimental animals by nitrosodimethylamine treatment. Heightening of adrenal cortical function was registered at two stages: at an early stage of carcinogenesis--two months after nitrosodimethylamine treatment, and during tumor progression--after 7 months. Cellular immunity inhibition was observed at the said periods.

[Critical conditions as a logical and appropriate series of events in iron methabolism disorders (the summary of experimental studies)].

It is revealed that in all models of critical conditions will activate the free-radical oxidation, decreasing the total antioxidant activity, the concentration of transferrin decreases in the serum of the blood, increase of the concentration of ferritin, the theological properties of the blood are violated and the signs of endothelial dysfunction are identified. Pre-entered deferoxamine in the dose of 80 mg/kg reduced the intensity of free-radical oxidation processes, restoring the antioxidant potential, concentration of the transferrin, and a lower level of ferritin, contributed to the normalization of blood theological properties and a reduction of the extent endothelium destruction as a result of the reduction Fe2+ concentration in blood serum.