Open Access Open Access  Restricted Access Access granted  Restricted Access Subscription or Fee Access

Vol 21, No 3 (2023)

Cover Page

Full Issue

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Reviews

Mechanisms of cellular protection against nanomaterials

Morozova O.V.

Abstract

Introduction. Entry of inorganic and organic nanomaterials through respiratory tract, skin and digestive system increases the risks of immunological disorders, hereditary and oncological diseases. Localization and stability of nanoparticles are determined by the mechanisms of inter- and intracellular vesicular transport.

The aim. Study of cellular uptake, targeted intracellular delivery, degradation and secretion of nanomaterials on the base of mechanisms of vesicular transport, unspecific innate resistance and adaptive immune response.

Results. Physical and chemical properties of nanomaterials determine their high reactivity and economy, penetration into organisms through all protective barriers and in any cells by means of endocytosis, macropinocytosis and phagocytosis. Concerns related to nanotechnology development include risks of: 1) cytotoxicity of nanomaterials, products of their cellular metabolism and delivered materials in nanocarriers; 2) immunological disorders resulted from immune status disbalance, chronic inflammation, allergic and autoimmune complications. Endocytosis and phagocytosis of nanomaterials cause destruction of foreign substances in lysosomes and secretion of free nanoparticles, extracellular vesicules and lysosomes containing nanoparticles. For intercellular exchange tunneling nanotubes are formed. Neutrophil extracellular traps provide barrier functions and deposition. Protection of organisms includes phagocytosis of nanomaterials, their detoxication in liver and spleen with subsequent excretion, and unspecific innate resistance with cytokine gene expression.

Conclusion. Natural mechanisms of cellular protection are based on nanoparticle degradation in lysosomes, secretion of foreign materials in free form, as part of extracellular vesicles or lysosomes, formation of tunneling nanotubes and neutrophil extracellular traps. Besides, antigen presentation causes cytokine gene expression resulting in protective reactions of organism.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):3-11
pages 3-11 views

Molecular mechanisms of neuroinflammation and sleep deprivation in the development of age-associated cognitive dysfunction

Nazarova K.E., Kostromina R.A., Malinovskaya N.A., Khilazheva E.D., Komleva Y.K.

Abstract

Introduction. Proinflammatory cytokines produced in elevated concentrations in the elderly significantly impair neurogenesis in the dentate gyrus of the hippocampus, long-term potentiality, alter neuronal morphology and function, and increase apoptosis. This leads to impaired episodic memory, executive function, and spatial learning, as well as neurodegeneration. Half of the elderly suffer from sleep disorders. Insomnia causes activation of microglia and increases 24-hour expression of proinflammatory cytokines, which enhances pre-existing inflammation, which in turn exacerbates insomnia.

Objective: to systematize scientific data on the role of sleep disorders in the development of neuroinflammation in the elderly, other causes and consequences of this condition, as well as on methods of insomnia correction in the elderly.

Material and methods: an analysis of the main foreign and domestic sources from PubMed/Medline, elibrary.ru databases was performed.

Conclusion. Aging is associated with the inevitable accumulation of cellular damage and depletion of endogenous mechanisms to eliminate DAMPs. Their excessive amount excessively activates NLRP3 inflammasome expressing proinflammatory cytokines. Chronic sleep deprivation in aging occurs because of disturbances in the interaction between sleep homeostatic mechanisms and circadian clock parameters, resulting in increased levels of proinflammatory cytokines. Increased levels of neuroinflammation impair the survival and proliferation of new neurons and their proper integration into pre-existing hippocampal neural networks encoding spatial information. Increased apoptosis, impaired gliogenesis, dendritic atrophy, and loss of synapses also contribute to the decreased size of the hippocampus in sleep disorders.

The use of behavioral strategies to improve sleep quality in the elderly (sleep hygiene, moderate exercise, and social activity) has been discussed to correct the negative effects of chronic neuroinflammation.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):12-21
pages 12-21 views

Original research

Predictive clinical and laboratory aspects of the relationship between the concentrations of iron, transferrin and ferritin in blood serum

Namiot E.D., Morozova G.D., Sadykov A.R., Logvinenko A.A., Yurasov V.V., Skalny A.V.

Abstract

Introduction. Assessment of the status of iron at the individual and population level is an urgent task. However, the interpretation of the results is associated with a number of difficulties. The inflammatory process, disorders of carbohydrate metabolism and other non-specific reactions of the body make it difficult to adequately characterize the status of iron.

A change in serum iron levels may be a predictor of the development of deficiency or excess of ferritin and transferrin. Conversely, ferritin and transferrin can act as predictors of iron deficiency or excess.

Purpose of the study. The purpose of the study was to identify the prognostic significance of the determination of iron, ferritin and transferrin in serum.

Material and methods. The study was performed on the basis of a database of laboratory analyzes taken in the course of laboratory practice. Ferritin, transferrin, and iron were measured in blood serum. The total number of laboratory tests for ferritin, transferrin, iron in serum was 4292. To assess the deficiency or excess of the analyzed analytes, we use the ROC curve model, which is widely used to determine the diagnostic value of new markers. In the present study, this is an attempt to indirectly assess iron metabolism in general, based on a minimum number of laboratory tests.

Results. Serum iron concentration may be a predictor of ferritin deficiency or excess. As well as feritin can be a predictor in the assessment of iron concentration. Here we have identified a strong gender dependence. The threshold values, which we calculated as the coefficient of the maximum values of the product of sensitivity and specificity, differ in men and women by more than seven times. For transferrin, we can predict an excess, but we cannot detect a deficiency. We can also predict iron deficiency based on transferrin values.

Conclusion. In our work, we show the possibility of a relationship between the content of iron, ferritin and transferrin in the blood serum, which, according to the results of laboratory tests, goes beyond the reference values.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):22-28
pages 22-28 views

Changes in retinal vascular structure and blood biochemical markers of modeled white rats in short-term arterial hypertension

Aliyeva G.V., Garaeva G.G.

Abstract

Introduction: Great progress has been made in the treatment of arterial hypertension (AH). However, despite the fact that new technologies have paved the way for practical medicine, the number of deaths and disabilities from diseases of the cardiovascular system continues to increase. Among these pathologies, hypertension occupies an important place.

Purpose of the study: To determine the correlation between changes in the content of creatinine, urea, residual nitrogen, the activity of creatine phosphokinase and lactate dehydrogenase enzymes in the blood in the initial stage of arterial hypertension and the vascular structure of the retina.

Material and methods: The research was carried out on 15 chinchilla rabbits weighing 3–4 kg, which were divided into 3 groups of 5 animals each. The concentration of creatinine, urea, residual nitrogen (ROA), activity of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) in the blood was determined using reagent kits manufactured by the Human company on a semi-automatic BioScreen-2000 device manufactured in the USA. Results and discussions: It was established that in intact rabbits (group 1) systolic pressure fluctuated within 100–130 mm Hg, and diastolic – within 70–84 mm Hg. Blood creatinine ranged from 70 mg/dL to 84 mg/dL, and urea concentration ranged from 10 mg/dL to 42 mg/dL. LDH activity varied widely from 230 to 430 U/L. The total area of arteries of medium diameter is 4800–5600 µm3, and their permeability is 150–290 km. As a result of the introduction into the vein of experimental animals included in the 2nd group for 3 days of ergometrine maleate, the level of blood pressure changed moderately compared to the 1st group. Against the background of a relatively moderate increase in blood pressure, the amount of creatinine in the blood increased by 5% compared with the 1st group. The concentration of urea increased by 12%. The activity of CPK in the blood increased significantly (4%) in contrast to OA. LDH enzyme activity increased significantly (10%) (p=0.05). In group 3, there was an increase in systolic and diastolic pressure. The amount of residual nitrogen increased significantly. Significant changes were observed in the concentrations of markers characterizing the functional state of the liver (CPK, LDH).

Conclusion. Thus, it can be concluded that short-term administration of ergometrine maleate moderately increases blood pressure.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):29-38
pages 29-38 views

Polypeptide effect on stimulation of experimental animals cellular proliferation

Ryzhak G.A., Chalisova N.I., Ivanova P.N., Egozova E.S.

Abstract

Introduction. The study of mechanisms of multicellular system regulation and of cellular proliferation and apoptosis balanced status in the organism tissues is one of the actual task of modern biology and medicine.

Purpose of study. Effect of polypeptide complexes (PPCs) from liver (Wentwil) and of bladder (Wesustim). and of corresponding short peptides. on the cellular proliferation in liver and bladder tissues of mammalian and birds.

Methods. Organotypic tissue culture of rat and 17-days chick embryo liver, bladder under different PPCs and short peptides was used for quick biologically activity of peptides screening.

Results. The tissue specific effect of PPC and short peptides on liver and bladder of different animals types. The square index (SI) of explants was increased statistically reliable on 21–29%, as compared to the control.

Conclusion. The data obtained produce the base for working and quick testing of preparations for treatment of patients with pathology in liver and bladder tissues.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):39-42
pages 39-42 views

Clinical and microscopic analysis of cellular-molecular communications in focal cortical dysplasia IIIс

Mitrofanova L.B., Rasulov Z.M., Vorobeva O.M., Gorshkov A.N., Sterkhova K.A., Ulitin A.Y.

Abstract

Cortical dyslamination with neuronal dysmorphism that occurs adjacent to an arteriovenous malformation (AVM) and is accompanied by epilepsy (E) is classified as FCD IIIc. Its etiology and pathogenesis have yet to be determined.

Objective: to clarify the cellular composition and expression of various receptors in the AVM and its perifocal zone with and without FCD IIIc

Material and methods. A morphological study of the surgical material of the brain of 14 patients with FCD IIIc and 13 patients with AVM without E was carried out using antibodies to: Ang1, Ang2, Ki-67, MHC1, CD34, NeuroD1, NG2, CD117, PrgRc, ErgRc, SSTR2, GH, SMA, GFAP and electron microscopy of the AVM of 1 patient with FCD IIIc.

Results. There were CD34+ endotheliocytes, CD34+/CD117+/NeuroD1+ telocytes, SMA+ smooth muscle cells, NG2+ pericytes in the walls of AVM vessels with E and without it. A scar zone of CD117+-telocytes forming a 3D structure was determined in 50% of patients with FCD IIIc and in 46% with AVMs. Electron microscopy confirmed the presence of pericytes and telocytes in the small AVM vessels. In no case was the expression of PrgRc, ErgRc, and GH, while SSTR2 was detected in vascular cells of all AVMs and the perifocal zone. The expression level of MHC1 was statistically significantly higher in the AVM vessels than around the vessels (p<0.001), and NeuroD1 was higher in the AVM vessels than in the vascular kidneys (p<0.001), while there were significantly more NG2+-pericytes in the perifocal zone than in AVM (p=0.02), and CD117+-telocytes – in AVM and perifocal zone than in vascular kidneys (p<0.001).

Conclusion. Our study made it possible to clarify the cellular composition of the AVM and its perifocal zone, revealing pericytes and telocytes; did not reveal differences in malformation with and without E. The pronounced expression of SSTR2 in AVM opens up new possibilities for therapy with somatostatin analogs.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):43-50
pages 43-50 views

System matrix metalloproteinase/inhibitors in pathogenesis of infiltrative pulmonary tuberculosis, depending on the resistance of Mycobacterium tuberculosis strains for anti tuberculosis therapy

Esmedlyaeva D.S., Alekseeva N.P., Dyakova M.E.

Abstract

Introduction. The search for molecular markers of adverse treatment outcomes in individuals with pulmonary tuberculosis (PT) is relevant due to the worldwide increase in drug resistance of Mycobacterium tuberculosis (MBT) strains to anti-tuberculosis drugs (PTP). Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) they are markers of destruction and remodeling.

The aim of the study. To study the features of the levels of the MMP in patients with infiltrative PT (IPT), depending on the MBT to PTP. To determine their significance as molecular markers of the effectiveness of therapy.

Methods. The concentrations MMP-1,-3,-8,-9 and TIMP-1 were measured using the ELISA method, kit «R&D Systems» (Minneapolis, MN, USA), the activity of α2-macroglobulin, neutrophils elastase (EL) – enzyme assays in the blood serum of 115 patients with ITL (58 drug – sensitive and 57 DR MBT). The effectiveness of the intensive phase of treatment was evaluated retrospectively. We used Statistica 10.0 (StatSoft, Inc.) and R.

Results. Regardless of the DR of MBT strains, patients with ITL have an imbalance in the MMP/inhibitors system towards proteinases. Regardless of the DR, the changes in circulating levels of MMP, TIMP-1 and EL were unidirectional with the otal volume of focuses and decay, as well as the number of neutrophils. Combinations from proteinase with results of chest X-rays methods of research at baseline levels in patients with ITL can be molecular prognostic markers of treatment outcomes.

Conclusion. The methods of multidimensional statistics showed that changes in the baseline levels of the MMPs and inhibitors in patients with ITL are not associated with the characterization of the resistance of MBT strains to the PTP, but are an objective criterion for the activity and prevalence of a specific process, and combinations from the MMP reflect the direction of its changes.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):51-57
pages 51-57 views

VDAC1-dependent mitochondrial effects of compounds containing the 4-hydroxy-3,5-di-tretbutyl phenyl substituent in experimental focal cerebral ischaemia

Pozdnyakov D.I.

Abstract

Introduction. Ischemic stroke is one of the most common causes of mortality and primary disability. The treatment of ischemic stroke, especially its complications, includes neuroprotective agents among which correctors of mitochondrial dysfunction stand out.

Aim of the study. To evaluate VDAC1-dependent mitochondrial effects of compounds containing 4-hydroxy-3,5-di-tretbutyl phenyl substituent in experimental brain ischemia.

Material and methods. Brain ischemia was modeled in Wistar rats by irreversible thermocoagulation of middle cerebral artery. After ischemia modeling, the tested compounds (7 objects) and reference drug ethylmethylhydroxypyridine succinate were administered orally (once in day) for 72 hours. After that time, the changes in concentration of ATP, apoptosis-inducing factor, caspase-3, mitochondrial hydrogen peroxide and VDAC1 in brain tissue were assessed in animals.

Results. In a study, were shown that the administration of studied compounds in animals with focal ischemia increased the ATP concentration while decreasing the content of mitochondrial hydrogen peroxide and the activity of caspase-dependent and caspase-independent apoptosis reactions. There was also found a decrease of VDAC1 concentration in animals treated with the analyzed compounds, which correlated with the changes of ATP concentration (r=0,89714), apoptosis-inducing factor (r=0,92367) and mitochondrial hydrogen peroxide (r=0,87629).

Conclusion. It was concluded that mitochondrial effects of compounds containing 4-hydroxy-3,5-ditrebutyl phenyl which manifested as decreased generation of mitochondrial reactive oxygen species, decreased intensity of reactions of internal apoptosis pathway and increased ATP concentration, were connected with the effect of these compounds on VDAC1 channel activity.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):58-64
pages 58-64 views

TREC and KREC in newborns of different gestational age

Ippolitova L.I., Ivantsova E.N., Kudlay D.A., Panichev K.V., Kokoreva S.P.

Abstract

Introduction. Primary immunodeficiency (PID) is a congenital disorder of the immune system that causes severe, chronic, autoimmune, infectious and oncological diseases with untimely diagnosis and treatment. Given that PIDs often do not have specific clinical manifestations, patients with this group of diseases are detected quite late, as a result of which the complications obtained can no longer be cured within the framework of standard treatment protocols. Thus, the introduction of additional studies into the neonatal screening program to determine the state of the T- and B-cell immunity link will avoid the development of severe complications in children with PID and will allow timely treatment to begin.

The aim of the study is to determine the TREC and KREC levels and their relationship with other indicators in newborns of different gestational ages..

Methods. This paper presents the results of the pilot program of neonatal screening of primary immunodeficiency in Voronezh and the Voronezh region. Markers of T- and B-cell lymphopoiesis were determined in 126 newborns by quantifying ring DNA molecules TREC and KREC by PCR-RV from dry blood spots on the basis of BUZ VOKB No. 1 PC, Building 1. Criteria such as gender, gestational age, body weight, total blood count (leukocyte count) at admission and closest to neonatal screening, CRP at admission and closest to neonatal screening, the presence of a burdened somatic and obstetric-gynecological history were evaluated; as a result, the main patterns in the dynamics of the KREC level were deduced and TREC in the study groups. Blood samples were obtained during the standard newborn screening program by collecting heel blood on special filter paper test forms – Guthrie cards.

Results. TREC and KREC levels increase with increasing gestation period, however, in all premature infants they remain below the established standard values. A significant increase in the detected indicators is observed precisely during the last weeks of intrauterine life. Evaluating the «body weight» indicator, it was found that the most frequently reduced levels of TREC and KREC were observed in newborns with a body weight of 1500–2000 g, less often in newborns weighing more than 2500 g. When evaluating the indicator «burdened obstetric and gynecological (OAG) and burdened somatic anamnesis (OSA)», it was revealed that in all selected groups, in 100% of cases, newborns had a history of OAG and OSA. Evaluating other compared criteria, it was found that the most frequently reduced levels of TREC and KREC were observed in newborns at 29–32 weeks gestation.

Conclusion. The dynamics of increasing the level of TREC and KREC increases with increasing gestation period and body weight, and already at 29–32 weeks (with a weight of more than 1500 g) becomes the most informative due to the fact that the pool of cells responsible for the implementation of cellular and humoral immunity can most adequately respond to various significant effects on the body.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(3):65-72
pages 65-72 views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies