Veterinary drug Trametin obtained on the basis of Trametes pubescens xylotroph fungi: its effect on the biosynthesis of interferons and its prophylactic activity against calf respiratory diseases

Given the spread of bacterial and viral diseases in young farm animals, the use of interferons and drugs to stimulate their biosynthesis has gained relevance. In a previous study, we examined the effect of a veterinary drug Trametin produced on the basis of Trametes pubescens (Shumach.: Fr.) Pilat. on the biosynthesis of interferons in the blood of mice. The present work is aimed at studying the biosynthesis dynamics of α- and γ-interferons when using Trametin and studying its prophylactic activity in calves. It is shown that a single oral administration of Trametin in doses ranging from 15 to 60 mg/kg causes a dose-dependent induction and production of γ-interferon in the blood of mice, whose maximum content reaches 1337.0±93.0 pg/mL at 48 h after administering a dose of 30 mg/kg. With a Trametin dose increase from 15 to 30 mg/kg, the level of α-interferon production rises to 1388.0±84.0 pg/mL at 48 h after administration. At a Cycloferon dose of 4.5 mg/kg, the production level of α-interferon and γ-interferon amounts to 1455.47±84.2 and 1447.0±90.0 pg/mL, respectively. The immunostimulatory properties of Trametin are confirmed by a scientific and economic experiment conducted using immunocompromised calves. In our studies, an immunological test of calf blood performed prior to and following the administration of Trimetin and Cycloferon constitutes criteria for the prophylactic activity of these drugs. The prophylactic efficacy of Trametin is confirmed by an increase in phagocytic activity by 10.5%, phagocytic index by 61.8%, and phagocytic number by 52.8%. After Trametin administration, the bactericidal activity of the serum increases by 60%. Cycloferon exhibits a similar immunostimulatory effect. Nonspecific prophylaxis using Trametin is shown to reduce the incidence of bacterial and viral respiratory diseases in young calves and generally improve their immunity.

Clinical and immunological studies of humoral factors of inflammation and regeneration in patients with injuries of the frontal and basal area

The authors conducted clinical and immunological research on the identification of сytokine factors of inflammation and regeneration in patients with frontal bone trauma (29) and practically healthy donors (11). Factors of inflammation (interleukin-1β, γ-interferon), anti-inflammation and regeneration (interleukin-34 and transforming growth factor – TGF-1β) were determined in the blood serum by ELISA. It was found that the content of the factor of regeneration decreases and the levels of anti-inflammatory cytokines increase in the blood serum of the patients with frontal traumas with frontal sinus damage.

RNASeq analysis of a Pax3-expressing myoblast clone in-vitro and effect of culture surface stiffness on differentiation.

Skeletal muscle satellite cells cultured on soft surfaces (12kPa) show improved differentiation than cells cultured on stiff surfaces (approximately 100kPa). To better understand the reasons for this, we performed an RNA Seq analysis for a single satellite cell clone (C1F) derived from the H2kb-tsA58 immortomouse, which differentiates into myotubes under tightly regulated conditions (withdrawal of γ-interferon, 37°C). As expected, the largest change in overall gene expression occurred at day 1, as cells switch from proliferation to differentiation. Surprisingly, further analysis showed that proliferating C1F cells express Pax3 and not Pax7, confirmed by immunostaining, yet their subsequent differentiation into myotubes is normal, and enhanced on softer surfaces, as evidenced by significantly higher expression levels of myogenic regulatory factors, sarcomeric genes, enhanced fusion and improved myofibrillogenesis. Levels of RNA encoding extracellular matrix structural constituents and related genes were consistently upregulated on hard surfaces, suggesting that a consequence of differentiating satellite cells on hard surfaces is that they attempt to manipulate their niche prior to differentiating. This comprehensive RNASeq dataset will be a useful resource for understanding Pax3 expressing cells.

A non-immunological role for γ-interferon–inducible lysosomal thiol reductase (GILT) in osteoclastic bone resorption

The extracellular bone resorbing lacuna of the osteoclast shares many characteristics with the degradative lysosome of antigen-presenting cells. γ-Interferon–inducible lysosomal thiol reductase (GILT) enhances antigen processing within lysosomes through direct reduction of antigen disulfides and maintenance of cysteine protease activity. In this study, we found the osteoclastogenic cytokine RANKL drove expression of GILT in osteoclast precursors in a STAT1-dependent manner, resulting in high levels of GILT in mature osteoclasts, which could be further augmented by γ-interferon. GILT colocalized with the collagen-degrading cysteine protease, cathepsin K, suggesting a role for GILT inside the osteoclastic resorption lacuna. GILT-deficient osteoclasts had reduced bone-resorbing capacity, resulting in impaired bone turnover and an osteopetrotic phenotype in GILT-deficient mice. We demonstrated that GILT could directly reduce the noncollagenous bone matrix protein SPARC, and additionally, enhance collagen degradation by cathepsin K. Together, this work describes a previously unidentified, non-immunological role for GILT in osteoclast-mediated bone resorption.

Immunomodulating properties of Cinnabsin

Introduction: Complex natural medicines are successfully used in various inflammatory diseases of the upper respiratory tract, but their immunomodulatory activity has not been studied enough, in particular in case of Cinnabsin. Therefore, the aim of the study was to determine the effect of the medicine on the production of cellular and humoral factors of immunity and inflammation by tonsil cells of the children. Materials and methods: The studies were performed in vitro using 24-hour cultures of children`s pharyngeal tonsil cells after adenotomy. Altogether 90 samples of cultures were examined before and after the influence of the medicine. The effect of complex natural medicine Cinnabsin on the cells production of various cytokine groups (γ-interferon, interleukins 1, 4, 10), expression of surface antigens CD14+, CD16+, and cytolytic activity of natural killer cells were investigated. Methods of enzyme immunoassay, light microscopy and cellular cytolysis with xenogenic targets were used. Statistical processing was carried out with the Student`s non-parametric criterion, and the Fisher`s angle transformation method when processing ratios. Results: Cinnabsin, both in dosage 10 μg/ml and 100μg/ml, increased the number of cells with the expression of the antigen CD16+ and partially CD14+, activated the natural cytotoxic cells of the tonsils, reduced the production of IL-1β and increased the production of IL-10 and γ-interferon in cell culture. Conclusion: According to the sum of the effects and the immunomodulation vectors, it is possible to state the modulating effect of the medicine on the activity of various immunity reactions, which allows concluding the pronounced anti-inflammatory and antiviral effect of Cinnabsin.

CELLULAR IMMUNITY AND CYTOKINE PROFILE IN PRE-FARROW AND LACTATING SOWS

Study results of cellular immunity and cytokine profile of commercial pre-farrow and lactating sows are shown. Before farrow, the animals demonstrated physiological immunodeficiency characterized by relative leukopenia and lymphopenia, decreased T-cell number, higher helper/suppressor ratio providing immunological tolerance in dam/fetus system. Their cytokine profile was specified by relatively deficient interleukin-1β and tumor necrosis factor-α indicative of immune system suppression and high level of γ-interferon involved in parturition and activation of suppressor cells. Post-farrow sows demonstrated higher cellular immunity involving higher levels of leukocytes, lymphocytes and T-cells as well as tendency of T-lymphocyte helper/suppressor ratio reduction being indicative of T-cells’ suppressor activity. The cytokine profile of the sows was specified by the recovered numbers of interleukin-1β, tumor necrosis factor-α and γ-interferon, decreased level of interleukin-2 and interleukin-4 that regulate cellular and humoral immunity, respectively as well as their subsequent increase (in particular, interleukin-2) following animal immunization against parvoviral infection and erysipelas on day 7 post farrowing (Parvoruvax vaccine, Merial, France) and against classical swine fever on day 14 post farrowing (culture dry virus-vaccine LK-VNIVIPFIT). This is due to the formation of the cellular and humoral immunity.

MONITORING OF MICROBIOLOGICAL AND IMMUNOLOGICAL DISORDERS IN UROGENITAL CHLAMYDIA IN INDIVIDUALS OF REPRODUCTIVE AGE

The identification and analysis of microbiological and immunological disorders in urogenital chlamydiosis of mixed etiology plays an important role in understanding the pathogenesis of the development of the chronic course of the disease with severe complications (infertility, miscarriage). Along with classical microbiological studies (isolating and studying the properties of the microbiota in mixed infections), the role of antigens of all participants of the infectious process (bacteria, viruses, fungi) in the occurrence of adequate immunological reactions (the level of interferon, γ-interferon) as indicators of the immune response.