Buccal Mesenchymal Stromal Cells as a Source of Osseointegration of Titanium Implants.

We studied the interaction of human buccal mesenchymal stem cells (MSCs) and osteoblasts differentiated from them with the surface of titanium samples. MSCs were isolated by enzymatic method from buccal fat pads. The obtained cell culture was presented by MSCs, which was confirmed by flow cytometry and differentiation into adipocytes and osteoblasts. Culturing of buccal MSCs on titanium samples was accompanied by an increase in the number of cells for 15 days and the formation of a developed network of F-actin fibers in the cells. The viability of buccal MSCs decreased by 8 days, but was restored by 15 days. Culturing of osteoblasts obtained as a result of buccal MSC differentiation on the surface of titanium samples was accompanied by a decrease in their viability and proliferation. Thus, MSCs from buccal fat pads can be used to coat implants to improve osseointegration during bone reconstruction in craniofacial surgery and dentistry. To improve the integration of osteoblasts, modification of the surface of titanium samples is required.

Studying the Proliferative Activity of Human Corneal Stromal Cell Populations.

The proliferative activity of populations of stromal cells (fibroblasts) obtained from human corneal lenticles under conditions of their differentiation into keratocytes was studied. It was shown that during differentiation, the number of dividing fibroblasts and the frequency of divisions, and motor activity of these cells (speed of movement along the cell trajectory and the length of the trajectory) sharply decreased. These findings indicate a decrease in the proliferative activity of fibroblasts under conditions of their differentiation and transformation into keratocytes. A period of 17 days is sufficient for differentiation of corneal fibroblasts into keratocytes.

Biocompatibility of Titanium Oxynitride Coatings Deposited by Reactive Magnetron Sputtering.

Titanium oxynitride coatings deposited by reactive magnetron sputtering improve biocompatibility of vascular stents by increasing NO production, viability, and adhesion of EA.hy926 cells. Thus, the application of titanium oxynitride coatings is a promising strategy for increasing the biocompatibility of nitinol stents.

Effect of Erythropoietin on Mononuclear Cells of the Bone Marrow and Spleen.

We studied the effect of preconditioning of human bone marrow mononuclear cells with erythropoietin on the immunophenotype of immunocompetent cells and paracrine activity of mouse splenocytes. The expression of erythropoietin receptors on immunocompetent human bone marrow cells was shown to change after a short-term (60 min) exposure to erythropoietin. The number of T helpers carrying erythropoietin receptors decreased and the number of T suppressors, B lymphocytes, and monocytes carrying erythropoietin receptors increased. The presence of 30% conditioned medium from human bone marrow mononuclear cells or 33.4 U/ml of erythropoietin reduced apoptosis/necrosis, increased intracellular activity of NADPH-dependent oxidoreductases of splenocytes, and did not affect oxidative phosphorylation (did not enhance lactate production and glucose uptake by cells).

Effect of Conditioned Media of Limbal Epithelial Cells and Corneal Stromal Cells on Functional Activity of Limb Mesenchymal Stem Cells.

We studied the effect of conditioned media from limbal epithelial stem cells, fibroblasts, and corneal keratocytes on the functional activity of human limbal mesenchymal stem cells. It was shown that the conditioned media from limbal epithelial stem cells reduced proliferative activity and inhibited migration of limbal mesenchymal stem cells. In the conditioned media of limbal epithelial stem cells, increased concentrations of VEGF and TNFα and reduced concentration of BDNF, vimentin, and fibronectin were found. The conditioned medium from corneal stromal cells did not affect functional activity of mesenchymal stem cells in the limbus. These data contribute to the understanding of the interaction of cells in the limbal niche and with corneal cells essential for the maintenance of the cellular homeostasis in the cornea.

Prenatal Stress and Adaptive Behavior of Offspring: The Role of Placental Serotonin.

The effect of mild prenatal stress in mice, leading to an increase in the placental serotonin level, on the formation of adaptive behavior in male offspring at the age of 35 days was studied. It was shown that, in BalbC mice, daily immobilization for 1 h during the period from 11 to 14 days of pregnancy led to an increase in placental and fetal serotonin levels on the 15th day of prenatal development. According to "resident-intruder" behavioral test, the prenatally stressed mice showed more reactive behavior in adulthood and low tendency to defend their territory. Thus, placental serotonin, formed under the stress condition, may act as a mediator between the environment and the fetuses and determine the adaptive behavior of offspring.

[Computed X-ray microtomography of the junction of dental implants with standard and custom abutments]. / Komp'yuternaya rentgenmikrotomografiya uzla soedineniya dental'nykh implantatov so standartnymi i individual'nymi abatmentami.

THE AIM OF THE STUDY: Comparative study of the precision of the junction of modern implant systems with standard and custom abutments. MATERIALS AND METHODS: The study was carried out by the method of computed X-ray microtomography on an X-ray microtomograph Heliscan micro CT using the ImageJ program in the laboratory «Systems for Microscopy and Analysis¼ of the Skolkovo Technopark. The measurement of the gap width between the implant and the abutment for each sample was carried out at 20 points according to the algorithm: the total length of the connection between the implant and the abutment; step (distance) between 5 equidistant points along the contact between the abutment and the implant; the measurements were repeated in 2 perpendicular sections along the joint node axis. The study was conducted on the example of seven implant systems common in Russia. The effect on the implant-abutment assembly of a multiple functional load of 250 N at an angle of 45° (7.6 million cycles) was studied. RESULTS: It has been established that the precision of the junction of modern implants with standard abutments is different and is characterized by the length of the contact from 268 to 1300 µm, the gap at the level of the platform from 5.0 to 11.7 µm, and the asymmetry of the contact in diameter by 2.4-14.2 µm. Abutments individually made in modern CAD/CAM laboratories do not have significant dimensional differences with standard abutments, but they have technological defects. The functional load expands and deforms the gap between the implant and abutment junction in the upper half of their contact. CONCLUSION: The results obtained demonstrate the capabilities of the computer X-ray microtomography method, which can be used to control the quality of manufacturing collapsible dental implants, the accuracy of manufacturing individual abutments in CAD/CAM laboratories, as well as in the development of new dental implant systems. The dimensional parameters of the junction node determine the advantages of the deep cone connection of the implant and the abutment.

Balamuthia spinosa n. sp. (Amoebozoa, Discosea) from the brackish-water sediments of Nivå Bay (Baltic Sea, The Sound) - a novel potential vector of Legionella pneumophila in the environment.

We have found a new free-living amoeba species named Balamuthia spinosa n. sp. (Amoebozoa, Discosea) in the bottom sediments of the brackish-water Nivå Bay (Baltic Sea, The Sound). This species resembles members of the genus Stygamoeba morphologically and was (mis)identified as belonging to this genus during the initial investigation. However, SSU rRNA gene data show that it robustly groups with Balamuthia mandrillaris sequence among Acanthopodida and represents a new species of the genus Balamuthia. Fragments of Legionella pneumophila genome were found among the NGS contigs obtained from B. spinosa n. sp., suggesting that this species may be a vector of Legionella in the environment. We discuss a remarkable morphological and ultrastructural similarity between the genus Balamuthia and the genus Stygamoeba. In addition, our phylogenetic analysis based on the SSU rRNA gene sequences revealed a close relationship between the genera Stygamoeba and Vermistella. It is one more confirmation of the order Stygamoebida, which was formed basing on the morphological evidence. The position of these branches close to Thecamoebida clade is congruent with current phylogenomic data.

Morphofunctional Properties of Corneal Stromal Cells.

Human corneal stromal cells were isolated by enzymatic digestion from a new source, lenticules obtained during laser vision correction by the ReLEx SMILe method. The resulting culture was mainly presented by fibroblast-like cells with a phenotype CD90-/CD73+/CD105+/keratocan-/lumican-/ALDH1A1+ that differentiate into keratocytes in a specialized medium. The concentration of fetal calf serum-derived growth factors affects the rate of proliferation, production of erythropoietin and brain neurotrophic factor by corneal fibroblasts, and to a lesser extent, their migration activity and production of extracellular matrix components. Thus, the high functional potential of fibroblast-like cells isolated from stromal lenticles can be used to develop cell technologies in ophthalmology.

Prognostic Value Estimation of Monoamines Systemic Level in Retinopathy of Prematurity in Experiment.

The aim of the investigation was to study a systemic level of L-DOPA, dopamine, and norepinephrine, and assess their prognostic value in retinopathy of prematurity (ROP) development on an experimental disease model. MATERIALS AND METHODS: The investigation was carried out on infant Wistar rats (n=36) divided into a study group (rat infants with experimental ROP, n=17) and a control group (n=19). The animals of both groups were sacrificed on days 14, 21-23, and on days 28-30. The choice of the indicated periods corresponded to the key stages of ROP development in an experiment and was based on the findings of our previous histological studies. Dopamine, L-DOPA, and norepinephrine levels in infant rat blood plasma samples were determined. RESULTS: On day 14 of the experiment (the period corresponds to the pathological neovascularization induction in the applied model and preclinical ROP in children), mean L-DOPA level in infant rats with ROP (0.31 ng/ml) was significantly decreased compared to that in the controls (0.42 ng/ml) (p≤0.01). On days 21-23 of the experiment (the period corresponds to the growth of pathological extraretinal neovascularization in the applied model and ROP stage 3 in children) the systemic level of L-DOPA was still statistically reduced in the study group (0.87 ng/ml) compared to the control group (1.53 ng/ml) (p≤0.01). On days 28-30 of the experiment (the period corresponds to the regress of neovasculature in the applied model and a spontaneous ROP regress stage in children) the L-DOPA level in blood plasma in the study group (0.33 ng/ml) showed an insignificant upward tendency in reference to the controls (0.21 ng/ml). Mean dopamine and norepinephrine levels had no difference in the groups under study of infant rats within all follow-up periods. CONCLUSION: Low systemic level of L-DOPA at the preclinical stage of experimental ROP should be considered as a laboratory prognostic criterion of a developing pathological process; it will enable to use the criterion when working out the measures to optimize the existing screening system for the disease in children.

Cytotoxicity of Xenogeneic Pericardium Preserved by Epoxy Cross-Linking Agents.

The aim of the study was to assess the cytotoxic effect of xenopericardial biomaterial treated with di- and pentaepoxides on the cell cultures in vitro. MATERIALS AND METHODS: Samples of bovine and porcine pericardium were used in the work. Three different modes were employed for preservation: 1) 0.625% solution of glutaraldehyde (GA) and a two-fold change on days 2 and 7; 2) 5% solution of ethylene glycol diglycidyl ether (EGDE) changed on day 2; 3) 5% EGDE solution for 10 days, then 2% pentaepoxide solution also for 10 days. The cytotoxicity of the biomaterial was assessed by the extraction method. To determine the cytotoxicity of the biomaterial, EA.hy926 cells, multipotent mesenchymal stem cells (MMSCs), and fibroblasts were used. Cell viability was determined by the MTT test. The level of apoptosis and necrosis in the cell cultures was assessed by staining with acridine orange and ethidium bromide after cultivation with xenopericardial extracts employing different modes of preservation. RESULTS: Extracts of bovine and porcine pericardium preserved with GA have been found to have the greatest toxic effect on the cell cultures showing 20-33% reduction of cell viability. Extracts from bovine and porcine pericardium preserved with di- and pentaepoxy compounds do not have a toxic effect on endothelial cells, MMSCs, and fibroblasts since cell viability reduction is by no more than 15%. The lowest level of apoptosis and necrosis is observed in the cell cultures under the influence of extracts from the pericardium, preserved with diepoxide and pentaepoxide compounds. CONCLUSION: According to the MTT test for cytotoxicity and determination of the level of apoptosis and necrosis in cell cultures, bovine and porcine pericardia treated with di- and pentaepoxides have been established to have no cytotoxic effect on the culture of endothelial EA.hy926 cells, MMSCs, fibroblasts in vitro, whereas GA, in comparison with di- and pentaepoxides, has a toxic impact on the cells.

A Comparative Analysis of CSF and the Blood Levels of Monoamines As Neurohormones in Rats during Ontogenesis.

According to the literature, the cerebrospinal fluid (CSF) in the cerebral ventricles contains numerous neuron-derived physiologically active substances that can function as neurohormones and contribute to volume neurotransmission in the periventricular region of the brain. This study was aimed at carrying out a comparative analysis of CSF and the blood levels of monoamines in rats during ontogenesis as an indicator of age-related characteristics of monoamine transport to body fluids and their function as neurohormones in volume neurotransmission in the periventricular region of the brain. We have shown that CSF in the perinatal period and adulthood contains the most functionally significant monoamines: dopamine, noradrenaline, and serotonin. A comparison of the monoamine levels in the CSF and blood of animals of different age groups revealed that CSF contains monoamines of predominantly neuronal (cerebral) origin and almost no monoamines derived from the general circulation. We also established that monoamines are found in the CSF at physiologically active levels that allow them to act as neurohormones in both reversible volume neurotransmission in the adult brain and irreversible regulation of brain development in the perinatal period.

Vannella primoblina n. sp. - an unusual species of the genus Vannella (Amoebozoa, Discosea, Vannellida) with pronounced dorsal ridges and folds.

Amoebae of the order Vannellida (Amoebozoa, Discosea) have a fairly recognizable spatulate, fan-shaped or semi-circular outlines and a wide area of frontal hyaloplasm. They can be easily distinguished from the other groups of lobose amoebae even by light microscopy. The dorsal side of these amoebae is usually smooth and rarely bears ridges or folds, which are never numerous or regular. We have isolated an unusual species of vannellid amoebae, called Vannella primoblina n. sp. from a terrestrial substrate. It has well-developed dorsal relief consisting of regularly appearing folds and ridges. This amoeba superficially resembles members of the genus Thecamoeba. However, molecular analysis showed that this strain belongs to the genus Vannella. This finding indicates that dorsal folds may also be a characteristic of some species of vannellid amoebae and probably are a functional detail of the cell morphology rather than an apomorphy of Thecamoebida lineage. Overall outlines of the cell and the presence of the expanded frontal hyaline area remains the most reliable characters used to differentiate vannellid amoebae from other gymnamoebae lineages.

Effect of Erythropoietin on Morphofunctional Properties of Mesenchymal Stem Cells.

We studied the effect of erythropoietin on the morphofunctional status of bone marrow mesenchymal stem cells in patients with coronary heart disease. It was shown that the duration of cell exposure with erythropoietin had different effects on the expression levels of adhesion molecules, erythropoietin receptors, and co-expression of the erythropoietin receptor and common ß-chain of cytokines, apoptosis/necrosis, and the cell cycle. In most cases, erythropoietin increased proliferation, migration, and NO production by "aged" mesenchymal stem cells (passage 8) and passage 4 mesenchymal stem cells grown during the previous 3 passages in the presence of 33.4 U/ml erythropoietin. Erythropoietin increased the expression of the autophagy marker LC3B in mesenchymal stem cells grown in the presence of erythropoietin in the culture medium. Thus, long-term culturing of mesenchymal stem cells in the presence of erythropoietin in the culture medium increased their resistance to adverse microenvironment factors - oxidative stress and hyperglycemia.

[Therapeutic potential of a biomedical cellular product in rats with lower limb ischaemia]. / Terapevticheskii potentsial biomeditsinskogo kletochnogo produkta pri ishemii nizhnikh konechnostei u krys.

Critical ischaemia of lower limbs is a cause of death and invalidity in the whole world. Stem cells and products of their secretion find wide application in treatment of vascular diseases, including critical ischaemia of the lower limbs. Erythropoietin promotes an increase in the angiogenic potential of stem cells. The authors examined the therapeutic potential of a biomedical cellular product (mesenchymal stem cells and products of their secretion) and mesenchymal stem cells with erythropoietin on the processes of restoration of vessels in the hind legs of Wistar male rats following induction of lower limb critical ischaemia. Mesenchymal stem cells were derived from the bone marrow of male Wistar rats. Critical ischaemia of hind legs was modulated by transaction of the femoral artery. The parameters of microcirculation in the foot were assessed with the help of laser Doppler flowmetry. In the blood serum and crural muscles by means of solid-phase enzyme immunoassay we examined the levels of cytokines, growth factors, and persistent metabolites of nitrogen oxide - nitrites. Muscles morphology and the number of blood vessels were assessed by the findings of histological examination. It was shown that the biomedical cellular product alone and in combination with erythropoietin stimulated angiogenesis. The results of Doppler flowmetry revealed restoration of the parameters of microcirculation in the lower limb by 35-75% of the baseline values. Besides, we observed a decrease of muscle necrosis, connective tissue proliferation, and an increase in the number of the vessels supplying the muscles in the experimental groups. It was also determined that the biomedical cellular product influenced the levels of cytokines in blood serum and crural muscles. Hence, the obtained findings proved the therapeutic potential of the biomedical cellular product in critical ischaemia of lower limbs.

Cytotoxicity of Aluminum-Silica Matrices Modified with Carbon Nanotubes.

We studied the effect of aluminum-silicon matrices modified with carbon nanotubes on proliferation and production of nitric oxide by splenocytes, thymocytes, and bone marrow mononuclear cells of female db/db mice. Synthesized matrices decreased cell proliferation and suppressed NO production by the studied cells.

Evaluation of the Effect of Plasma from Patients with Trophic Ulcers on the Function of Dermal Fibroblasts, Mesenchymal Stem Cells, and Endothelial Cells.

We studied the effect of platelet lysate and platelet-poor plasma from patients with trophic ulcers with and without type 2 diabetes mellitus on proliferation, migration, and apoptosis of human dermal fibroblast, mesenchymal stem cells, and endothelial cells. It is shown that plasma obtained from patients with type 2 diabetes mellitus produced inhibitory effects.

[Discriminant analysis in establishing the relationship of pathogenetic mechanisms of gestational complications in urogenital infection in pregnant women.] / Дискриминантный анализ в установлении взаимозависимости Ð¿Ð°Ñ‚Ð¾Ð³ÐµÐ½ÐµÑ‚Ð¸Ñ‡ÐµÑÐºÐ¸Ñ Ð¼ÐµÑ Ð°Ð½Ð¸Ð·Ð¼Ð¾Ð² развития Ð³ÐµÑÑ‚Ð°Ñ†Ð¸Ð¾Ð½Ð½Ñ‹Ñ Ð¾ÑÐ»Ð¾Ð¶Ð½ÐµÐ½Ð¸Ð¹ при урогенитальной инфекции Ð±ÐµÑ€ÐµÐ¼ÐµÐ½Ð½Ñ‹Ñ .

The aim of the work - to establish the interconnection and interdependence of toll-like mediated pathogenetic mechanisms of urogenital infection in pregnant women from the position of epigenomics. Using discriminant analysis in 89 patients with urogenital infection in pregnant women for the first time was established a reliable evidence-based relationship and interdependence between mucosal immunity, the severity of the infectious process, clinical manifestations, symptoms of miscarriage in the background of simultaneous development of the infectious process and pregnancy. For urgent delivery (infection), urgent childbirth (infection and clinical manifestation) and premature birth, mucosal immunity determines the severity of anti-infective resistance (with increasing mucosal immunity oppression of infectious process and clinical manifestations is logged , and its decrease increases the severity of infection process and clinical manifestations); the inhibition of mucosal immunity prevails over its hyperreaction (inhibition of mucosal immunity is determined by the physiological immunodepression in response to the development of pregnancy, as well as in response to herpes virus infection when activated); the severity of the infectious process depends on the severity of clinical manifestations and symptoms of miscarriage. During miscarriage mucosal immunity provides the pathophysiological course of infectious process and the clinical manifestations and development of symptoms of misacrriage; increasing levels of mucosal immunity to hyperreaction contributes to the development of symptoms of abortion and miscarriage; not registered mutual influence of oppression, mucosal immunity and its hyperreaction; the severity of the infectious process does not depend on the severity of clinical signs and symptoms of miscarriage. In urgent childbirth (infection), the oppression of mucosal immunity does not affect the severity of clinical manifestations, symptoms of abortion and the infectious process. In urgent or premature birth, and termination of pregnancy, the oppression of mucosal immunity affects the severity of clinical manifestations, the severity of the infectious process and the symptoms of abortion; the severity of clinical manifestations and the severity of the symptoms of abortion are interrelated. In urgent birth (infection) mucosal immunity overreaction affects the severity of clinical manifestations, symptoms of miscarriage and infection; in case of term and preterm labour overreaction mucosal immunity on the severity of infection and symptoms of abortion and does not affect the severity of clinical manifestations and at the termination of a pregnancy mucosal immunity on the severity of the infectious process and does not affect the severity of clinical signs and symptoms of abortion. The levels of mucosal immunity inhibition, its hyperreaction, clinical manifestations, symptoms of pregnancy termination and the severity of the infectious process do not depend on the type of herpes simplex virus. In the absence of infection with herpes simplex virus in patients with urogenital infections of pregnant women, there is no mutual influence and the relationship between the oppression of mucosal immunity and hyperreaction of mucosal immunity, the oppression of mucosal immunity prevails over its hyperreaction. With increasing mucosal immunity oppression, increased anti-infectious resistance of the body (the decreased activity of the infectious process), and with its decrease decreased (increased activity of the infectious process). Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms, clinical manifestations and infectious process, and also determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of the infectious process did not affect the clinical manifestations. During infection with herpes simplex virus type I or type I and II on the background prevalence of oppression mucosal immunity over hyperreaction mucosal immunity, the presence of relationships between them, and the impact of mucosal immunity on the severity of the infectious process and the clinical manifestations increase mucosal immunity has been shown to decrease the severity of infection and clinical manifestations (reduction of anti-infective resistance), while reducing mucosal immunity the severity of infection and clinical manifestations increased. Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms and determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of clinical manifestations reflects the severity of the infectious process. In type I and type II of pregnancy, the level of mucosal immunity determines the anti-infectious resistance of the body in urogenital infection of pregnant women. Inhibition of mucosal immunity and its hyperreactions are interrelated, have an impact on each other, as a result of their integral interaction, increasing the levels of mucosal immunity leads to a decrease in the severity of clinical manifestations and the infectious process, reducing the levels of mucosal immunity contributes to the manifestation of clinical manifestations, as well as increasing the severity of the infectious process. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process and clinical manifestations determine the severity of the symptoms of abortion. In type III and type IV of pregnancy course, there is no mutual influence of mucosal immunity oppression and its hyperreaction. The levels of indicators of mucosal immunity oppression and its hyperreaction are interrelated; the increase in the severity of mucosal immunity oppression is accompanied by a decrease in clinical manifestations and severity of the infectious process and vice versa. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process determines the severity of the symptoms of abortion and clinical manifestations, acting as a leading component of gestational complications in urogenital infection of pregnant women. In the III type of pregnancy course oppression of mucosal immunity does not affect the severity of symptoms of miscarriage. In the IV type of pregnancy course, the levels of mucosal immunity oppression prevail over the indicators of mucosal immunity hyperreaction, which is due to the integral interaction of physiological inhibition of immunological reactivity of the organism in response to pregnancy and inhibition of immunological reactivity of the organism, accompanying the activation of infectious process of viral genesis. Hyperreaction of mucosal immunity determines the symptoms of abortion.

Interconnection of bacterial and phytoplanktonic communities with hydrochemical parameters from ice and under-ice water in coastal zone of Lake Baikal.

We analysed the relationship between the chemical complex (concentration of dissolved ions, nutrients, pH) and biological parameters (primary production, biomass of phytoplankton, abundance and activity of bacterial communities) at estuaries of rivers and coastal waters of Southern Baikal during the under-ice period. Correlation network analysis revealed CO2 to be the main limiting factor for the development of algae and microbial communities in the coastal zone of Lake Baikal. This study indicates that primarily reverse synthesis of bicarbonate and carbonate ions associated with the development of phytoplankton and accumulation of dissolved CO2 during photosynthesis regulates pH in the Baikal water. We did not detect the anthropogenic factors that influence the change in pH and acidification. Near the Listvyanka settlement (Lake Baikal, Listvennichnaya Bay), there was a great number of organotrophs and thermotolerant bacteria with low bacterioplankton activity and high concentration of organic carbon. This evidences eutrophication due to the influx of organic matter having an anthropogenic source. Nutrients produced during the bacterial destruction of this matter may explain the changes in bottom phytocenoses of Listvennichnaya Bay.

Cytokines of the Lymph and Blood Serum as Markers of Oncogenesis and Efficiency of Therapy in Chemically Induced Breast Cancer in Wistar Rats.

We studied the levels of serum and lymph cytokines involved in the pathogenesis of BC. BC was induced by injection of N-methyl-N-nitrosourea to Wistar rats. The animals underwent surgery, or received polychemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil), or surgical treatment was combined with polychemotherapy; in a special group, Panagen (fragmented DNA) was added to polychemotherapy. Cytokine concentration in the lymph was measured using Bio-Plex Pro Rat Cytokoness 24-Plex Assay test system (Bio-Rad). In rats with BC, the content of most studied cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, MIP-1α, MIP-3α, RANTES, TNFα, and MCP-1) in the lymph and blood was significantly higher, while the content of IL-10 and GRO/KC was lower than in intact animals. Surgical resection of the tumor led to a significant decrease in the content of both pro- and anti-inflammatory cytokines in the lymph. Polychemotherapy led to a significant decrease in the content of IL-1ß, IL-4, IL-6, IL-7, MIP-1α, MIP-3α, and RANTES in the serum and lymph. Comparison of the cytokine content in the serum and lymph of operated animals after polychemotherapy with and without Panagen showed that the content of most cytokines (IL-5, IL-6, IL-7, IL-10, IL-13, IL-17A , IL-18, GRO/KC, IFNγ, and MIP-3α) was higher after Panagen administration.