Medical academic journal

Mixed saliva is an important barrier preventing pathogens invasion. Despite many years of research on the protective factors of saliva, the functional significance of some of them has not yet been disclosed. The fraction of proline-rich proteins and their proteolytic fragments are the major component in mixed saliva, but the functions of these peptides still remain poorly understood. Various diseases of the oral cavity are a common problem for humans, especially for elderly patients, which undoubtedly determines the relevance of studies aimed at clarifying the role of protective molecules of the innate immunity — antimicrobial peptides and poorly studied cationic proline-rich polypeptides in the pathogenesis of these diseases. The purpose of the review is summarizing the data available in the literature revealing the molecular mechanisms of the participation of certain protein components of mixed human saliva — antimicrobial peptides (alpha- and beta-defensins, cathelicidin, histatins, etc.) and proline-rich cationic proteins and peptides (secrets of the parotid glands) in the implementation of its protective functions at normal conditions and under various types of pathology. Based on the analysis of the literature, we can conclude that when studying the biological activity of protective factors of mixed saliva, it is necessary to take into account that each of these compounds implements its effects in tight interaction with other salivary components, modulating their activity. In particular, it can be assumed that functions of proline-rich proteins and peptides of the oral fluid are largely carried out as a result of intermolecular interactions with antimicrobial peptides.

BACKGROUND: To determine the severity of the condition of the victims exposed to the chemical factor of the fire, they are guided by the content of carboxyhemoglobin in the blood. Inhalation exposure of combustion products of polymeric materials with pulmonotoxic effect leads to disruption of the structure and function of the respiratory system, which plays an important role in aggravating the condition of the victims and predicting the outcome.

AIM: To identify the features of determining the severity of the condition of victims exposed to the chemical factor of fire, depending on the calculated initial concentration of carboxyhemoglobin in the blood and the presence of interstitial changes in lung tissues.

METHODS: When conducting a retrospective analysis of the medical histories of victims exposed to the chemical factor of fire, the initial concentration of carboxyhemoglobin in the blood was calculated, X-rays of the chest cavity organs performed on the first day after admission were analyzed.

RESULTS: Depending on the calculated initial concentration of carboxyhemoglobin in the blood, patients with severe (59 [55; 60]%), moderate (42 [36; 43]%) and mild (18 [15; 24]%) severity. The duration of hospitalization of patients did not depend on a certain degree of severity. It was found that the duration of hospitalization (5 [4; 8] days) of patients with interstitial changes in the lungs detected on radiographs (47 ± 7% of victims) was higher (p = 0.03) compared (3 [2; 5] days) with patients in whom interstitial changes were not detected (53 ± 7% of victims). A moderate correlation (r = 0.31, p < 0.05) was determined between the duration of hospitalization of patients and the presence of interstitial changes on the part of the respiratory system.

CONCLUSION: The presence of interstitial changes in lung tissues identified during radiography should be considered as an unfavorable prognostic sign and taken into account when organizing medical care for victims exposed to the chemical factor of fire.

BACKGROUND: According to modern concepts, the kisspeptin signaling system is the upper (central) link in the regulation of reproductive function. The neuropeptide kisspeptin is considered an indicator of a number of obstetric pathologies in humans. Therefore, it should be considered important to search for new synthetic analogues of natural kisspeptins as pharmacological agents of reproduction regulation. On the other hand, it should also be considered important to search for new effective model organisms in which certain effects manifest themselves most prominently compared to traditional experimental animals.

AIM: To quantify the effect of kisspeptin-14 on the level of gonadoliberin and progesterone in two doses, at the time typical for the action of neuropeptides, on the model organism Danio rerio.

METHODS: In this study, an analogue of kisspeptin, conventionally designated kisspeptin-14, was used. All Danio rerio females had reached puberty by the time of the experiment (6–8 months). Kisspeptin was administered in doses of 1 and 4 ng. The groups were analyzed 1 and 4 hours after administration. Before administration of the preparations, the fish were subjected to lidocaine anesthesia at a concentration of 40 mg/l for 5–6 minutes, then the drug was administered intracerebroventrically. After waiting for 1 or 4 hours, the material was collected (gonads and midbrain). Gonad and midbrain samples were homogenized, homogenates were suspended, and enzyme immunoassay was performed to determine hormone concentrations.

RESULTS: Administration of kisspeptin-14 at a dose of 1 ng led to an increase in gonadoliberin levels 4 hours after administration. With a shorter time after administration, no statistically significant results were found. Administration of kisspeptin-14 at doses of 1 and 4 ng led to an increase in progesterone levels in the gonads of Danio rerio females 1 and 4 hours after administration. At the same time, statistically significant differences compared with the control group were noted at different sample collection dates.

CONCLUSION: Intracerebroventricular administration of the kisspeptin-14 at a dose of 1 ng after 4 hours causes an increase in gonadoliberin in the structures of the midbrain. Intracerebroventricular administration of kisspeptin-14 causes an increase in progesterone in the gonads of Danio rerio females. There was no unambiguous relationship between changes in the concentration of gonadoliberin in the structures of the midbrain and changes in the concentration of progesterone in the gonads of females.

BACKGROUND: One of the obstacles in successful radiation therapy of malignant tumors is the emergence of cell subpopulation that have lower radiosensitivity than the original tumor. Use of fractionated irradiation in this case leads to a possibility of the radioresistant cells to substitute the initial cell population. We assume that changes in epigenetic profile of a cell affect chromatin packaging in the cell nucleus. This in turn represents changes leading to formation of the radioresistant phenotype.

AIM: The aim is to study the structure of nuclei of a subpopulation of Ehrlich adenocarcinoma cells with a radioresistant phenotype.

METHODS: In the present study the cells of ascitic Erlich adenocarcinoma have been sequentially irradiated in the PX-γ-30 (source is ⁶⁰Co, dose output is 0.87 Gy/min). Then the cells have been inoculated into female outbred mice ICR (CD-1). Irradiation of the original population of Erlich adenocarcinoma showed that cells were losing an ability to transplantation after a dose of 20 Gy. In the series of irradiations with a gradual dose increase (from 10 to 40 Gy) there was obtained a cell subpopulation that retains an ability to transplantation after a dose of 40 Gy. The original and radioresistant cell subpopulations were tested for sensitivity to ionizing radiation. Nuclei were collected from these cells for further structure investigation with the method of small angle X-ray scattering (SAXS).

RESULTS: Analysis of SAXS data of the nuclei showed no significant changes in nucleus structures of Erlich adenocarcinoma initial cells that survived irradiation with doses of 20 and 30 Gy. At the same time, Erlich adenocarcinoma cells that survived irradiation with a dose of 40 Gy demonstrated abnormally low fractal dimension on mass fractal mode (in a size of 40–200 nm).

CONCLUSION: Observations of chromatin packing variations well conform with data obtained by biological characterization of researched samples and appear as a crucial aspect of understanding mechanisms of radioresistance occurrence.

BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide. Chronic heart failure is accompanied by hemodynamic disturbances, including alterations in blood microrheological properties. Changes in erythrocyte deformability may lead to impaired activation and interaction of platelets and neutrophils, contributing to thrombosis and the progression of chronic heart failure.

AIM: Determination of neutrophil activity and thrombus formation in an ex vivo model of thromboinflammation in patients with chronic heart failure with simultaneous assessment of blood microrheology.

METHODS: The study involved 21 patients with a diagnosis of chronic heart failure and 8 healthy volunteers. The patients and volunteers underwent determination of the biochemical composition of blood plasma and assessment of the condition of the blood elements. The thromboinflammation was evaluated in whole heparinized blood using parallel-flat flow chambers coated with type I collagen at a shear rate of 100 1/s. The deformability parameters of erythrocytes were measured in vitro using the method of laser diffractometry. Erythrocyte aggregation was determined by diffuse light scattering from whole blood samples.

RESULTS: For thrombus areas, no statistical differences were found between healthy controls and patients with chronic heart failure. However, the neutrophil velocities for patients with chronic heart failure were significantly lower than for healthy controls (0.11 ± 0.02 µm/s for chronic heart failure versus 0.16 ± 0.04 µm/s for healthy controls). The thrombus areas for patients with chronic heart failure at 5 and 10 minutes of growth correlated with the concentration of red blood cells and the average volume of red blood cells. Also, the aggregation coefficients of erythrocytes A1 and A2 characterizing the intensity of the process of formation of linear and three-dimensional aggregates positively correlated with thrombus area. In addition, mean corpuscular volume, erythrocyte deformability indices, and yield strength of the erythrocytes correlated with neutrophil movement velocities.

CONCLUSION: Thus, although there is no significant change in thrombus formation in chronic heart failure, however, we can talk about a decrease in neutrophil activity, possibly associated with the increase in blood viscosity.

BACKGROUND: The innate immune response plays a crucial role in protecting the organism against viral pathogens, important part of which are pattern recognition receptors, such as Toll-like and RIG-I-like receptors. It is known that viral invasion, including influenza virus infection, leads to the activation of intracellular pattern recognition receptors such as TLR3, TLR7, TLR8, and TLR9, which are localized in the endoplasmic reticulum, endosomes, and lysosomes, as well as MDA5 and RIG-I, which are cytosolic sensors of viral RNA not associated with cell membranes. The expression of these genes, their proper functioning, and regulation are of critical importance for ensuring an adequate immune response and the establishment of antiviral protection.

AIM: The aim of this study is to develop and validate a quantitative PCR system for assessing the expression of TLR3, TLR7, TLR8, TLR9, MDA5, and RIGI genes in mouse tissues and organs.

METHODS: Gene expression levels were analyzed using reverse transcription polymerase chain reaction with specially developed panels of primers and fluorescent probes. For approbation were selected female inbred BALB/c albino mice aged 8–10 weeks, infected with influenza A/PR8/34 (H1N1) virus.

RESULTS: In this study, a test system based on multiplex polymerase chain reaction was developed for assessing the expression of endosomal receptor genes TLR3, TLR7, TLR8, and TLR9, as well as cytosolic sensors MDA5 and RIG-I. The amplification efficiency was 99 for TLR3, 106 for TLR7, and 107% for the remaining genes. This test system was used to study the expression levels of TLRs and RLRs in the lung and spleen tissues of BALB/c mice infected with influenza A/PR8/34 (H1N1) virus. According to the obtained results, 24 hours post-infection, a significant change in mRNA levels of TLR3, TLR7, TLR8, TLR9, and MDA5 was observed in the lungs but not in the spleens of infected animals.

CONCLUSION: The developed test system can be used for analyzing the expression of certain intracellular PRRs, providing opportunities for a deeper investigation of the pathophysiological mechanisms underlying the immune response.

The article is dedicated to Academician of the USSR Academy of Medical Sciences Petr S. Kupalov, an outstanding scientist-physiologist, neurobiologist, student, associate and successor of I.P. Pavlov, Honored Scientist, who headed the I.P. Pavlov Physiology Department of the Institute of Experimental Medicine for 27 years. P.S. Kupalov devoted his entire scientific career to the further development of the physiology of higher nervous activity, significantly enriching the understanding of the subtle mechanisms of the brain with new research methods, relying on Pavlov’s classical postulates of the theory of conditioned reflexes. P.S. Kupalov is the developer of the concept of “shortened conditioned reflexes”, ideas about the “dynamic stereotype”, and the methodology of situational conditioned reflexes. P.S. Kupalov preserved the legacy of his teacher for history: from the texts of Pavlov’s lectures on general physiology to fundamental works on the physiology of digestion and higher nervous activity, the tradition of educating young scientists and scientific and organizational work, presenting the scientific achievements of domestic scientists at international forums and in the foreign press. But subsequently the name of P.S. Kupalova was undeservedly forgotten. This publication is an attempt to restore historical justice in relation to a great scientist and remarkable person.