Recombinant Pneumolysin of Pneumococci Induces TLR4 Expression and Maturation of Dendritic Cells In Vitro.

Pneumolysin (Ply) is a target for the development of serotype-independent pneumococcal vaccines, an important condition for the efficacy of which is their ability to activate innate immunity with the subsequent formation of adaptive immunity. In this study, the ability of recombinant full-length Ply (rPly) of pneumococci to induce TLR expression and maturation of dendritic cells generated from mouse bone marrow was evaluated. It was shown that rPly in vitro increased the number of dendritic cells expressing Toll-like receptor 4 (TLR4) on the membrane. rPly caused maturation of dendritic cells generated from mouse bone marrow, which manifested in a decrease in the number of progenitor cells (CD34), an increase in the number of cells expressing the adhesion molecule CD38, costimulatory molecules CD80 and CD86, molecules of terminal differentiation of dendritic cells CD83, as well as molecules of antigenic presentation of the major histocompatibility complex class II.

State of the art: Russia starts genome-edited plant assessment.

Russia has started the process of correcting its GMO regulation, but it does not use the same approach to regulating genome-edited plant products as other countries. Our assessment here is based not only on science but also on important social and economic factors.

Use of Mathematical Methods for the Biosafety Assessment of Agricultural Crops.

In Russia and around the world, there are important questions regarding the potential threats to national and biological safety created by genetic technologies and the need to improve or introduce new, justified, and adequate measures for their control, regulation, and prevention. The article shows that a significant volume of the global market is occupied by five major transgenic crops, and producers are ready to switch to crops with an edited genome that has been approved in the United States, Argentina, and other countries. We propose a qualitatively new approach to the risk assessment of edited plants, "Safe Design," and we have also developed an extremely important, fundamentally new approach to the development of methods that combine next-generation sequencing (NGS) and Bioinformatics for the assessment of the crop import biosafety. The proposed mathematical approach provides a detailed analysis of the possible insertions of DNA fragments into the genome of edited crops and a clarification of their biological significance. The developed method can be used in the rapid screening of plants for the presence of potentially dangerous genes, viral sequences, and nonspecific promoter sequences.

Carbohydrate Specificity and Isotypes of Monoclonal and Polyclonal Antibodies to Conjugated Tetrasaccharide, a Synthetic Analogue of Repeating Unit of Capsular Polysaccharide of Streptococcus Pneumoniae Serotype 14.

We studied carbohydrate specificity and isotypes of antibodies to BSA-conjugated tetrasaccharide, a repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 14, in mouse polyclonal sera and hybridoma-synthesized products. Natural IgM antibodies to the tetrasaccharide containing epitopes similar to surface carbohydrate structures of mammalian and human cells in low titers were determined in native mouse serum by ELISA using biotinylated tetrasaccharide and synthetic capsular polysaccharide as the solid-phase antigens. Polyclonal sera to the conjugated tetrasaccharide contained IgM and all subclasses of IgG antibodies, which were detected in a higher titer when the biotinylated tetrasaccharide was used as a solid phase antigen compared to synthetic capsular polysaccharide. Monoclonal antibodies to S. pneumoniae serotype 14 tetrasaccharide were identified in an equivalent titer using either biotinylated tetrasaccharide or synthetic capsular polysaccharide. Monoclonal antibodies obtained in vitro belonged to IgM isotype and cross-reacted with secondary full-size IgG antibodies. In the serum of mice inoculated with hybridoma, IgM and IgG2a antibodies recognizing the tetrasaccharide epitope in the structure of synthetic capsular polysaccharide were simultaneously determined.

[The effect of bisphosphonate therapy on reducing the risk of cardiovascular complications associated with chronic heart failure, type 2 diabetes and osteoporosis in postmenopausal women].

AIM: To study the effectiveness of oral alendronate and ibandronate bisphosphonates for the prevention of cardiovascular complications in postmenopausal women with type 2 diabetes mellitus (DM) and osteoporosis during a 12-month prospective observation. MATERIALS AND METHODS: The study included 86 women with osteoporosis, chronic heart failure (CHF) and type 2 diabetes: the 1st group (n=52) included patients who received basic therapy for heart failure; the 2nd group (n=34) included patients who, in addition to the basic therapy of heart failure, were prescribed alendronic and ibandronic acid preparations for the treatment of osteoporosis. In order to identify the possibility of associating the studied factors with the nature of the course of heart failure, the patients were divided according to the results of a one - year follow - up into two subgroups: subgroup A (n=49) - patients with a favorable course of the disease and subgroup B (n=37) - patients with an unfavorable course of pathology. RESULTS AND DISCUSSION: After 12 months, a significant decrease in the levels of cerebral natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-α, and interleukin-1ß was found in the group of women treated with bisphosphonates compared to baseline. Significant associations of NT-proBNP levels (p=0.02) and the studied cytokines (p=0.01) with an unfavorable course of heart failure were revealed. A significant association of bisphosphonate therapy with a favorable course of heart failure (p=0.01) was also revealed. The probability of developing adverse cardiovascular events during the year in the treatment of heart failure with basic therapy drugs with additional therapy of osteoporosis with bisphosphonates is significantly (p=0.0025) lower than the treatment of patients with heart failure with only basic therapy and not taking bisphosphonates for the treatment of osteoporosis. CONCLUSION: In postmenopausal women with associated cardiovascular pathology (CHF, type 2 diabetes and osteoporosis), prophylactic therapy with oral alendronate and ibandronate oral bisphosphonates is effective, reduces the risk of progression of heart failure, inhibits inflammatory mediators, positively affects the combined endpoints of comorbid cardiovascular pathology.

The hypothalamo-hypophysial system in Acipenseridae. IX. Formation of monoaminergic neurosecretory cells in the preoptic nucleus region during early ontogeny.

"Falck-positive" monoaminergic neurosecretory cells (M-NSC) are found in stage I-II sturgeon larvae in the dorsal zone of the preoptic nucleus (PN) by means of fluorescence and electron microscopy. Single poorly differentiated M-NSC are located mostly among the ependymal cells. At this stage the M-NSC have very short dendrites protruding into the third ventricle. In the process of differentiation the M-NSC move subependymally and their dendrites become longer. Axons of the M-NSC can be clearly traced only in stage IV larvae. Perikarya and dendrites of M-NSC contain little rough endoplasmic reticulum and numerous neurosecretory granules (NSG) 60-150 nm in diameter. Ventricular dendrites of the "Gomori-positive" peptidergic neurosecretory cells (P-NSC) containing NSG 110-200 nm in diameter are observed within the PN in stage III larvae. Thus the M-NSC differentiate earlier than the P-NSC. The intraventricular terminals have kinocilia and show typical macroapocrine secretion. This fact supports the view of a receptory as well as a secretory function of the M-NSC and P-NSC. It is proposed that in early ontogeny monoamine as well as peptide neurohormones are secreted into the cerebrospinal fluid. This transventricular pathway is considered phylogenetically ancient.

Ultrastructure of neurosecretory cells at different stages of differentiation in the preoptic nucleus of immature sterlet.

Ultrastructure of neurosecretory cells of the preoptic nucleus in immature sterlet (Acipenser ruthenus L.) was studies for the first time. The dorsal zone of the preoptic nucleus houses light, dark, and pycnomorphic neurosecretory cells, which contain varying numbers of elementary secretory granules measuring 1995 plus or minus 32 A in diameter. Light cells containing numerous secretory granules with a diameter of 1707 plus or minus 27 A are predominant in the middle zone. Pycnomorphic cells are absent in this zone. The ventral zone contains only poorly differentiated cells with solitary elementary granules measuring 1100-1300 A in diameter. The neurosecretory cells also differ with respect to the number and structural characteristics of their organoids. Thus, neurosecretory cells in the preoptic nucleus are found in different morphofunctional states, a circumstance that reflects the sequence of their development in ontogenesis and different phases of the secretory cycle.