[Possibilities of effective interaction in the system pharmacovigilance at registration of medicinal undesirable reactions at patients of the senior age groups.].

In recent years, complications of drug therapy are an important medical problem. Data on adverse drug reactions (ADR) in patients of older age groups were analyzed. The object of the study was notification cards for unwanted reactions received from medical organizations of the Irkutsk region for period 2009-2020 years.

Agonist-Induced Ca Signaling in HEK-293-Derived Cells Expressing a Single IP Receptor Isoform.

In mammals, three genes encode IP receptors (IPRs), which are involved in agonist-induced Ca signaling in cells of apparently all types. Using the CRISPR/Cas9 approach for disruption of two out of three IPR genes in HEK-293 cells, we generated three monoclonal cell lines, IP3R1-HEK, IP3R2-HEK, and IP3R3-HEK, with the single functional isoform, IPR1, IPR2, and IPR3, respectively. All engineered cells responded to ACh with Ca transients in an "all-or-nothing" manner, suggesting that each IPR isotype was capable of mediating CICR.

Metabolic response of broiler chickens to different doses of ICIS 96 in the diet.

The competitiveness and profitability of the poultry industry in market conditions are hampered by growing problems with the safety and quality of poultry meat. The use of targeted microbial preparations can assist in resolving these problems. Numerous studies of the properties of bacteria of the genus have shown their effectiveness in the practice of poultry farming.

Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells.

Here, we present DNA aptamers capable of specific binding to glial tumor cells , , and for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies.

Modeling of Ca transients initiated by GPCR agonists in mesenchymal stromal cells.

The integrative study that included experimentation and mathematical modeling was carried out to analyze dynamic aspects of transient Ca signaling induced by brief pulses of GPCR agonists in mesenchymal stromal cells from the human adipose tissue (AD-MSCs). The experimental findings argued for IP/Ca-regulated Ca release via IP receptors (IPRs) as a key mechanism mediating agonist-dependent Ca transients. The consistent signaling circuit was proposed to formalize coupling of agonist binding to Ca mobilization for mathematical modeling.

Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner.

The phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (LY294) and its much less active analog LY303511 (LY303) constitute the paired probe that is commonly used to demonstrate the involvement of PI3K in intracellular signaling. We studied effects of LY294 and LY303 on Ca signaling initiated by certain GPCR agonists in cells of several lines, including CHO cells expressing the recombinant serotonin receptor 5-HT2C and mesenchymal stromal cells derived from the human adipose tissue (AD-MSCs) and umbilical cord (UD-MSCs). The LY294/LY303 pair exerted apparently specific effects on responsiveness of AD-MSCs to ATP, suggesting the involvement of PI3K in ATP transduction.

Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia.

The amyloid-degrading enzyme neprilysin (NEP) is one of the therapeutic targets in prevention and treatment of Alzheimer's disease (AD). As we have shown previously NEP expression in rat parietal cortex (Cx) and hippocampus (Hip) decreases with age and is also significantly reduced after prenatal hypoxia. Following the paradigms for enhancement of NEP expression and activity developed in cell culture, we analysed the efficacy of various compounds able to upregulate NEP using our model of prenatal hypoxia in rats.

Genome Sequence of Enterococcus faecium Strain ICIS 96 Demonstrating Intermicrobial Antagonism Associated with Bacteriocin Production.

We report here the complete genome sequence of strain ICIS 96, which was isolated from the feces of a horse. Bacteriological characterization of strain ICIS 96 revealed the absence of pathogenicity factors, while its spectrum of antagonistic activity was found to be broad, having activities associated with both Gram-positive and Gram-negative bacteria. Analysis of the ICIS 96 genome revealed five genes associated with antimicrobial activity (enterocin [ent] A, ent B, lactobin A/cerein 7b, and ent L50 A/B).

[The effect of hypoxia on cholinesterase activity in rat sensorimotor cortex].

This study reports the dynamics of changes in postnatal ontogenesis of the activity of soluble and membrane-bound forms of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in sensorimotor cortex of rats as well as the pattern of their changes after prenatal hypoxia (E14, 7% O2, 3 h) or acute hypoxia in adult animals (4 months, 7% O2, 3 h). In normally developing rats the activity of the membrane-bound AChE form in the sensorimotor cortex gradually increased up to the end of the first month after birth and remained at this high level during all further postnatal ontogenesis, while the activity of the soluble form of AChE reached its maximum on the 10th day after birth and decreased significantly by the end of the first month. In animals exposed to prenatal hypoxia the activity both of the soluble and membrane bound forms of AChE during the first two weeks after birth was 20-25% lower, as compared to controls but increased by the end of the first month and even exceeded the control values remaining increased up to old age (1.

Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues.

Due to an increasing life expectancy in developing countries, cases of type 2 diabetes and Alzheimer's disease (AD) in the elderly are growing exponentially. Despite a causative link between diabetes and AD, general molecular mechanisms underlying pathogenesis of these disorders are still far from being understood. One of the factors leading to cell death and cognitive impairment characteristic of AD is accumulation in the brain of toxic aggregates of amyloid-β peptide (Aβ).

[The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer's disease].

Objective: To analyze the activity of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and neprilysin (NEP) in the blood serum in elderly people with different types of cognitive impairment and evaluate the effect of ceraxon on the biochemical parameters.

Material And Methods: Three groups of patients: without cognitive disorders (controls--CG), with amnestic mild cognitive impairment (а-MCI) and with Alzheimer's disease (AD were studied).

Results And Conclusion: The activity of AChE, BChE and NEP was reduced in the blood serum of patients with a-MCI and, to the greater extent, in patients with AD compared to CG and correlated with the level of cognitive dysfunction evaluated by MMSE, ADAS-cog, and other tests.

Modeling of the general astigmatic Gaussian beam and its propagation through 3D optical systems.

The paper introduces the complete model of the general astigmatic Gaussian beam as the most general case of the Gaussian beam in the fundamental mode. This includes the laws of propagation, reflection, and refraction as well as the equations for extracting from the complex-valued beam description its real-valued parameters, such as the beam spot radii and the radii of curvature of the wavefront. The suggested model is applicable to the case of an oblique incidence of the beam at any 3D surface that can be approximated by the second-order equation at the point of incidence.

Effect of hypoxia/ischemia and hypoxic preconditioning/reperfusion on expression of some amyloid-degrading enzymes.

Alzheimer's disease (AD) is linked to certain common brain pathologies (e.g., ischemia, stroke, and trauma) believed to facilitate its development and progression.