bluuebunny/crossref_metadata_2025 huggingface dataset:
T-dependent RMF Model Applied to Ternary Fission Studies
Authors: Kokila C. , Karthika C. , Balasubramaniam M.
Published: October 2021

Ternary decay is comparatively a rare phenomenon. The yield distribution for the thermal neutroninduced fission of 236U was investigated within the Temperature-dependent Relativistic Mean Field (TRMF) approach and statistical theory. Binding energy obtained from TRMF for the ground state and at a specific temperature is used to evaluate the fragment excitation energy, which is needed to calculate the nuclear level density. Using the ternary convolution, the yield for α-accompanied fission of 236U* is calculated. Initial results are presented which shows a maximum yield for the fragment pair Tc + Ag +α. Further, the ternary pre-existence probability for the spontaneous fission of 236U was studied considering fixed third fragments of α,10Be and 14C using the area of the overlapping region. No significant change in the yield distribution was observed when fragment deformations are considered. However, the heavy group for the probable pair remains as 132Sn with a change in mass number of the lighter fragment.
The Forgotten meme. On the example of Life and works of Placyd Jankowski
Authors: Chłopek Patryk
Published: October 2021

Placyd Jankowski (known also as John of Dycalp) was a popular writer active in the 1840s, he quickly gained popularity thanks to his humorous lyrics, but before his death in 1872 he was almost forgotten by readers. This raises questions about the rules guiding cultural memory. One of the concepts that could explain the process of cultural heredity is the memetic theory proposed by Richard Dawkins. The scholar assumes the existence of cultural units subject to the process of evolution, which he called memes. Their success and survival depend on the fulfillment of specific characteristics to which the human mind is particularly susceptible, i.e. topicality, originality, narrative, and universality. Using the tools developed by memetics, the article will attempt to describe the reasons for social forgetting on the example of the life and work of Placyd Jankowski.
Z aktora kapłan. Od „Króla-Ducha” do „słowiańskiego papieża”
Authors: Jeznach Klaudia
Published: October 2021

This article is concerned with the fragmentary nature of Juliusz Słowacki’s poem “Król‑Duch”, its mystical‑Christian dimension and the impact it had on Karol Wojtyła. Openness to infinity and perpetuality of literature is made clear by referring to Friedrich Schlegel and his idea on the endlessness of romantic poetry, as well as to Roland Barthes, who draws attention to the text as a fabric creating a “wonderful image”. “Król‑Duch”, being a work that requires a patient and soulful reader, ready to travel through the labyrinth, is noticed by Karol Wojtyla, who recognizes the poem as a perfect Christian epic. Participation in the Rhapsodic Theater and the change that occurred in the thought of the later pope indicate a deep understanding of the truths hidden in the work. It also proves that a new way of reading – a long conversation with the text, can lead to repentance. The article attempts to prove that literary mysticism, the experience of the relationship of the “I” with God, as well as spiritual activity bring the work of the romantic poet closer to the poetry of Karol Wojtyła, while making John Paul II the next “King‑Spirit”, the Spirit that orients the nation towards the highest levels of Divine Love.
Jazyková stránka diskusí mladých křesťanů v kyberprostoru
Authors: Bogoczová Irena , Maršík Lukáš
Published: October 2021

The present article introduces the results of the analysis of texts by Czech (Catholic) Christian young adults published in 2019 and 2020 on the website signaly.cz. This page is intended to unite Christians and support them in their faith. The texts are diverse in genre, their content is purely religious or secular, but it at least remotely touches on the issues of the spiritual life of man or his/her religiosity (“soft spirituality”). Posting on the internet testifies to the need for young people not only to strengthen themselves and others in their faith in God, but also to share trivial content that relates to daily life and behind which (in the background) they see God’s will, the expression of God’s love and wisdom.
Obraz Romů a jejich postavení v České republice popsané prostřednictvím polských turistických průvodců
Authors: Zormanová Michaela
Published: October 2021

The present article is based on the analysis of the content of Polish tourist guides to the Czech Republic or its parts. The topic of the analysis is the image of members of the Roma ethnic group, their position in the Czech Republic and the attitude of the majority society towards this minority. The guides mostly evaluate his attitude as negative and point to a number of prejudices and stereotypes towards this ethnic group.
Применение метода перевернутого обучения в дистанционном вузовском обучении делового русского языка
Authors: Vráželová Viktoria , Alieva Lenka
Published: October 2021

The paper deals with the problematics of the flipped classroom method in distance university education. It describes the differences between traditional and innovative forms of teaching in the course of business Russian outlining their main advantages and disadvantages. The emphasis is put on the application of the flipped classroom method in an online distance course as well as on the analysis of the data obtained from a questionnaire.
Effectiveness of different therapies for drug-related osteonecrosis of the jaw
Authors: González-Muñoz M. , Rodríguez-Archilla A.
Published: October 2021

Background. Antiresorptive drug-related osteonecrosis of the jaw (ADRONJ) is a serious complication of cancer patients or osteoporosis, under treatment with antiresorptive drugs. At present, there is no scientific evidence or consensus on the most appropriate treatment approach depending on the stages of the ADRONJ.
Objective. To assess the effectiveness of the different therapeutic options in the treatment of ADRONJ. Search methods. The following electronic databases were searched: PubMed (MEDLINE, Cochrane Library), Web of Science (WoS) and Spanish Medical Index (IME).
Selection criteria. Studies with results on treatment of ADRONJ.
Data analysis. Descriptive statistics were carried out considering means and percentages.
Results. 52 studies on treatment of ADRONJ were included in this review. The complete resolution of ADRONJ cases was observed in 205 of 257 patients (79.8%) treated with surgery plus flaps; 202 of 253 (another 79.8%) with the suspension of the antiresorptive drug (“drug holiday”); 512 of 648 (79.0%) with extensive surgery; 41 of 59 (69.5%) with adjuvant hyperbaric oxygen therapy; 462 of 680 (67.9%) with conservative surgery; 55 of 119 (46.2%) with laser therapy and, finally, 100 of the 346 patients (28.9%) achieved complete resolution with medical treatment (antibiotics + antiseptics).
Conclusions. Depending on the severity of bone exposures, surgical treatment combined with flaps appears to be the best therapeutic option for the treatment of ADRONJ.
Geomorphometry of the physical and geographical microregion of the Polkowice Hills
Authors: Bidzińska Paulina
Published: October 2021

In this paper, a morphometric analysis of the terrain sculpture was carried out along with the editing of a geomorphometric map of the physical and geographical microregion of the Polkowickie Hills, which so far was not present in the literature for the studied area. The analysis was performed using the GIS program (ESRI ArcMap), which is based on a digital elevation model (LiDAR - DEM). Following primary topographic parameters were selected through digital elevation model processing: aspect, slope, planar curvature, vertical curvature and local height diff erece, which provide exact information about the variability of the topography and its surface morphological processes. The obtained results of primary parameters allowed for the classifi cation of relief forms in the studied area using the unsupervised ISODATA classifi cation method. The fi nal stage consisted of editing a geomorphometric map of the Polkowickie Hills microregion and a presentation of the distribution of morphometric classes with the height division of boundaries of the obtained geomorphometric separations.
The results of the calculations and analyses allowed for the separation of various areas in the Polkowice Hills, and giving them their own names by the author. The choice of the unsupervised classifi cation method and the independent defi nition of the number of classes gave positive results of terrain clustering of the studied area. The compliance of the results of the selected classifi cation method with the actual topography (of which the author has extensive fi eld and observational knowledge) confi rms the selection of appropriate geomorphometric indicators and the unsupervised classifi cation method, which in the examined case turned out to be computationally eff ective.
Two methods to mitigate insar-based dems vegetation impenetrability bias
Authors: Tulski Sławomir , Bęcek Kazimierz
Published: October 2021

Digital elevation models (DEM), including the Shuttle Radar Topography Mission (SRTM), are used in many branches of geoscience as an ultimate dataset representing our planet’s surface, making it possible to investigate processes that are shaping our world. The SRTM model exhibits elevation bias or systematic error over forests and vegetated areas due to the microwaves’ peculiar properties that penetrate the vegetation layer to a certain depth. Numerous investigations identifi ed that the penetration depth depends on the forest density and height. In this contribution, two methods are proposed to remove the impact of the vegetation impenetrability eff ect. The first method is founded on the multiple regression of two forest characteristics, namely forest height and forest density. The second method uses a lookup table approach. The lookup table and the multiple regression explanatory variables are taken from the freely available datasets, including the forest density data (MODIS_VCF) and global tree height map (GTHM). An important role in this research is played by the Ice, Clouds, and Land Elevation Satellite (ICESat) data. The accuracy tests indicate that the fi rst method eliminates approximately 68% of the elevation bias, while the second method appears to be more effective, leading to almost complete removal of the vegetation bias from the SRTM data. The methods are fi ne-tuned to the local coniferous forests in Poland. Additional studies are required to fi netune the methods for the leaf-off state of deciduous forests. However, a new set of parameters for both methods can be quickly developed for diff erent locations and forest types. Both methods’ functionality and eff ectiveness can be improved once more accurate forest tree height and vegetation density data become available. These methods are universal in mitigating the vegetation bias from the Synthetic Aperture Radar Interferometry (InSAR) derived model and photogrammetric models.
CLINICAL AND IMMUNOLOGICAL EFFECTIVENESS OF TREATMENT OF RAGWEED POLLINOSIS IN THE SAMARA REGION
Authors: Zhukova N. N. , Manzhos M. V. , Khabibulina L. R. , Syrtsova E. Yu.
Published: October 2021

Allergic rhinitis and bronchial asthma are widespread respiratory allergic diseases. In some territories of the Russian Federation, the dominant cause of pollinosis is ragweed. The aim of the study was to evaluate the clinical and immunological efficacy of ASIT with the allergen Ambrosia artemisiifolia in patients sensitized to Ambrosia trifida in the Samara region. Patients with proven sensitization to Ambrosia trifida was held immunotherapy with Ambrosia artemisiifolia allergoid preseason. After treatment, patients had a decrease in the severity of symptoms of allergic rhinitis according to VAS (p = 0.00001), a decrease in the need for medications (p = 0.0003), as well as the need for corticosteroids against the background of therapy from 34.6% to 0% (p = 0.00001). In 8% of cases, the result of treatment was good, in 69% satisfactory, in 23% unsatisfactory. In the control group, there were no changes in the severity of symptoms (p = 0.858). Also, in the control group, the need for medications remained unchanged and 14.3% of patients continued to use corticosteroids.

After ASIT, there was a decrease in the level of IL-4 (p = 0.002), and a decrease in the ratio of IL-4/ IL-10 (p = 0.0063); at the same time, changes in the level of other cytokines (IL-10; IFNγ) were statistically insignificant (p > 0.05). Before treatment, the levels of IL-4/ IL-10 in both groups were comparable, and after treatment, the differences became statistically significant (p = 0.031). We did not get a statistically significant change in the level of IgG4 Amb a 1 or IgG4 Amb trifida. There was no correlation between the level of individual cytokines and the results of treatment. As a result of the conducted ASIT, positive clinical and immunological results were obtained. In most patients, the disease has acquired a controlled course. At the same time, the lack of excellent and low number of good results of ASIT is probably due to the intraspecific allergenic properties of ragweed.
CELLULAR IMMUNITY PARAMETERS IN PATIENTS WITH REMITTING MULTIPLE SCLEROSIS
Authors: Ivanova I. P. , Dyomina D. V. , Davydova M. N. , Seledtsova G. V.
Published: October 2021

The aim of this work was to study some parameters of cellular immunity in patients with multiple sclerosis (MS). The study included 10 patients with relapsing-remitting MS aged 32 to 50 years. Diagnosis was clinically established and confirmed by magnetic resonance imaging. Patients did not receive immunosuppressive therapy for at least 6 months prior to study entry. The neurological status of all examined patients was assessed using the Kurtzke functional scale using the Extended Disability Scale (EDSS) and averaged 4.0±0.67 points, the mean number of exacerbations per year was 1.25±0.25. While studying such parameters of the immune status such as the number of T, B, NK-cells, the content of immunoglobulins, the phagocytic activity of monocytes and granulocytes, their production of reactive oxygen species, no significant differences were observed in patients with MS in comparison with the normal donor level. At the same time, we have noted an increase in the proliferative response of mononuclear blood cells to myelin antigen by 2.35 times. The content of CD4+CD45RO+CD62L+ and CD8+CD45RO+CD62L+ central memory T-cells, as well as CD8+CD45RO+CD62L- effector memory T-cells in the blood of MS patients significantly exceeded the control values (p < 0.05). Also, in MS patients, compared with healthy individuals, there was an increased level of naive IFNγ-positive CD4+CD45RO- and CD8+CD45ROT-cells (p < 0.01), and an increase in CD4+CD45RO+ and CD8+CD45RO+ memory T-cells producing IFNγg or IFNγg together with IL-4 in response to the activation (p < 0.01). Consistent with these data, there were significantly increased serum IFNγ and IL-17 levels and no changes in IL-4 levels. The relative level of naive CD4+CD25+FoxP3+, as well as induced CD4+CD25- FoxP3+ regulatory T-cells in MS patients did not significantly change compared to donor values. The results of assessing some parameters of the immune status in MS patients indicate a functional reshaping of the immune system towards the Th1 type of immune response. It is obvious that immunotropic treatment of MS should be aimed at inactivating auto-immune Tand B-lymphocytes, suppressing the production of proinflammatory mediators, and enhancing the activity of natural and induced regulatory T-cells.
CHARACTERIZATION OF CENTRAL AND EFFECTOR CD4⁺ MEMORY CELLS IN PSORIASIS
Authors: Kolerova A. V. , Mikailova D. A. , Beimanova M. A. , Blinova E. A.
Published: October 2021

Psoriasis is a chronic autoimmune disease in which the skin and joints are involved in the pathological process. It was found that the recurrence of rashes in this disease occurs due to the resident memory cells of the skin. The number of CD4+CCR3+ effector memory cells in peripheral blood correlates with the severity of the disease. Therefore, the aim of our work is to study the phenotype of peripheral blood memory cells in patients with psoriasis.

The study included 6 healthy donors: average age – 45.4 (min – 29, max – 55), women – 3, men – 3; 10 patients with psoriasis: women – 4, men – 6, average age – 37.3 (min – 23, max – 57), of which 5 patients with PASI > 10 and 5 patients with PASI < 10. The exclusion criteria for the study were the presence of autoimmune, oncological and hematological diseases, systemic therapy with immunosuppressive drugs for 1 month. Patients signed informed consent to participate in the study. Isolation of peripheral blood mononuclear cells was performed in a density gradient of ficoll-urographin (p = 1.082 g/L). Then cells were stained with fluorochrome-conjugated monoclonal antibodies to surface markers of central (Tcm) and effector (Tem) CD4+ memory cells (CD4, CD45RO, CD197), the α-chain of the IL-7 receptor (CD127), and the γ-chain of the IL-7 receptor (CD132). Statistical analysis of the data obtained was performed using the Statistica 6.0 software package.

The percent of Tcm in the peripheral blood of donors was 33.4% (in – 18.2, max – 43.7), Tem – 28.7% (min – 13.6, max – 38.9), in patients with psoriasis: Tcm – 28.65% (min – 13.3, max – 59.6), Tem – 21.5% (min – 9.3, max – 38.6). In the peripheral blood of patients with psoriasis, among the central CD4+ memory cells, the proportion of CD127+CD132- -cells is 26.00%, CD127+CD132+ – 1.69%, CD127+CD132- – 69.00%, CD127- CD132+ – 1.94%. Among effector CD4+ memory cells, the proportion of CD127+CD132- -cells is 23.58%, CD127+CD132+ – 1.18%, CD127+CD132- – 69.84%, CD127- CD132+ – 0.70%. A direct correlation was found between the number of CD127- CD132+ central memory cells and the PASI value (r = 0.639, p < 0.05).

In patients with psoriasis, the proportion of central memory cells is higher than in healthy donors, while the number of effector memory cells is lower. A direct correlation was found between the number of central cells expressing the γ-chain of the IL-7 receptor and the severity of the disease. Activated memory cells are characterized by high expression of CD132. It can be assumed that this population of memory cells plays a role in maintaining autoimmune inflammation in patients with this disease, and also participates in the repopulation of skin resident memory cells.
EFFICACY OF IMMUNOMODULATORS AND ANTIOXIDANTS IN THE CORRECTION OF IMPAIRED IMMUNE STATUS PARAMETERS IN PATIENTS WITH ADENOMYOSIS
Authors: Ivanova O. Yu. , Telegina O. V. , Konoplya A. A.
Published: October 2021

The aim of the study was to study the effectiveness of the use of immunomodulators and antioxidants in the correction of immune status parameters in patients with adenomyosis. 70 patients were examined, including 57 women (the main group), who were diagnosed with adenomyosis according to the results of a comprehensive clinical, ultrasound and hysteroscopic examination. The control group consisted of 23 gynecologically healthy women. After verification of the diagnosis, all patients with hypertension received standard treatment (SL) (clinical recommendations of the Ministry of Health of the Russian Federation from 2016). Among the female patients, 19 women received only SL (1st subgroup). 38 exhaust gases examined, in addition to SL, received various combinations of antioxidant, immunomodulator, and membrane protector and were divided into two subgroups. The second subgroup included 20 patients in addition to the SL receiving sodium ribonucleate; Hypoxene and phospholipids. The third subgroup included 18 patients who additionally received Inosine + Nicotinamide + Riboflavin + Succinic acid; Meglumine acridone acetate, and glycyrrhizic acid + phospholipids. The analysis of the cytokine status and the compliment system was performed at the time of admission and by the 15th day of observation. Detected changes of the cytokine status, complement system activation, increased oxygen-dependent activity of neutrophils in the peripheral blood (increased production of active oxygen forms as a result of respiratory burst) confirm the presence of immune inflammation on the systemic level. Insufficient clinical-laboratory efficacy of ST in the correction of immune changes has justified the use of drugs with immunomodulating, antioxidant, and membrane protective properties in the pharmacological therapy of adenomyosis, which have been successfully used in the treatment of other diseases with similar disorders.Optimal combinations of immunomodulators and antioxidants in the correction of the immune status of patients with adenomyosis were revealed. The study performed demonstrates the efficacy of correcting immune status parameters in patients with adenomyosis when the standard treatment is combined with antioxidant and immunomodulating agents.
EMBRIOGENESIS OF NEURONAL ELENENTS (GLIOBLASTS AND GABAA RECEPTORS) IN THE HUMAN BRAIN NEUROIMMUNE SYSTEM UNDER PRENATAL ALCOHOL EXPOSURE
Authors: Shushpanova T. V. , Solonsky A. V. , Shumilova S. N. , Shushpanova O. V. , Bokhan N. A.
Published: October 2021

Exposure to alcohol causes imbalances in neuroimmune function and impaired brain development. Alcohol activates the innate immune signaling pathways in the brain. Neuroimmune molecules expressed and secreted by glial cells of the brain (microglia, oligodendroglia) alter the function of neurons and further stimulate the development of alcoholic behavior. Various signaling pathways and brain cells are involved in the transmission of neuroimmune signals. Glial cells are the main sources of immune mediators in the brain, which respond to and release immune signals in the central nervous system. The aim of this study was to study neuronal elements: morphometric parameters of glioblasts, synaptic structures and properties of synaptosomal GABAA-benzodiazepine receptors of the neuroimmune system in the embryogenesis of the human brain under perinatal exposure to alcohol. Changes in glioblasts in the brain tissue of human embryos and fetuses were revealed under conditions of chronic prenatal alcoholization with an increase in gestational age compared with control subgroups: a significant increase in the average number of glioblasts, the length of the perimeters of presynaptic terminal structures, postsynaptic density, presynaptic terminal regions were significantly less (p < 0.01) in the study group than in the control comparison group. Exposure to ethanol leads to a decrease in the affinity of GABAA-benzodiazepine receptors, which affects neuronal plasticity associated with the development and differentiation of progenitor cells (glioblasts and neuroblasts) during embryogenesis of the human brain and leads to suppression of GABAergic function in the brain. This causes a disruption in the interconnection of embryonic cells in the brain, leads to excessive apoptosis due to the activation of glial cells of the nervous tissue, disruption of neuroimmune function in the developing brain, changes in neuronal circuits, as well as a change in the balance of excitatory and inhibitory effects, which affects the functional activity in the central nervous system. Glial activation is a compensatory reaction caused by neuroplastic changes aimed at adapting the developing brain of the embryo and fetus under conditions of neurotoxicity and hypoxia under the influence of prenatal alcoholization of the maternal organism and the effect of ethanol on the fetus. The dynamics of changes in glial elements and receptor activity in the nervous tissue of human embryos and fetuses under conditions of prenatal exposure to alcohol indicates a more pronounced effect of alcohol on the earliest stages of human embryo development, which is of great practical importance in planning pregnancy and the inadmissibility of alcoholization of the mother in order to avoid negative consequences in offspring.
EFFICIENCY OF THE FORMATION OF ANTITUMOR IMMUNE RESPONSES IN THE SYSTEM OF PREVENTIVE VACCINATION OF MICE WITH TESTICULAR ANTIGENS
Authors: Dorzhieva A. B. , Khabalova T. S. , Androsova Yu. E. , Kaschenko E. A. , Ivanova I. P. , Seledtsova G. V.
Published: October 2021

Аppearance of a malignant tumor is associated with impaired mechanisms of proliferation, differentiation, apoptosis ability. However, these changes are not enough for immune system to recognize and destroy mutated cells. Weak immunogenicity of tumor-associated antigens (TAA) and the insufficiency of co-stimulating molecules on the surface of tumor cells is a reason for this phenomenon Since biochemical processes of tumor cells and healthy tissue cells are identical, therefore creation of effective chemotherapeutic drugs is limited not by selectivity of their action. So antitumor vaccination is the most effective specific method for both preventing recurrence of a disease and a therapeutic treatment tool in oncology. Xenogeneic proteins are highly immunogenic and effective in breaking immune tolerance to human analogs. In our work, we used sheep testicular AG as a source xenogenic TAAs. Sheep testicles contain a large set of TAAs. Experimental mice were immunized with type liposomal testicular vaccine from sheep, one month after vaccination, to induce tumor growth, cells of carcinoma LLC were implanted in mouse. The life expectancy of the experimental group of mice was 2 times higher compared to the syngenetic control and 20% of them did not develop the tumor at all. In the spleen of mice who did not have tumors after pre-vaccination sheep liposomal testicular AG, T-regulatory cells and T-memory cells were measured. We found a credible decrease in both naive Treg (CD4+CD25+), activated (CD4+CD25+FoxP3+) and both T-memory (CD4+CD44+) and central memory (CD4+CD44+CD62L+) in spleen pre-vaccination mice with compared to the contral intact spleen. Content of IFNg and IL-10 in supernatants of mouse slenocytes derived from vaccinated mice with no tumors was investigated and showed a reliable decrease in the amount of IL-10, but not IFNg. We believe that immunization with xenogenic tumor AGs can lead to the formation of a protective antitumor response.
FATTY ACID RECEPTOR GPR84 AND Th1/Th2 BALANCE IN THE EXPERIMENTAL SYSTEM IN VIVO
Authors: Demchenko E. N. , Gavrilova E. D. , Goiman E. V. , Volckiy N. N.
Published: October 2021

While conducting numerous studies, including researchers in our laboratory, it was found that Th1/Th2 balance plays an essential role in the regulation of reactions that determine the outcomes of immunopathological processes in both chronic and acute GVHD models. However, the question about activity of which element in the regulatory process during GVHD induction (for example, a receptor or an enzyme) affects the ratio of this balance depends remains open. It has been suggested that the degree of activation of the GPR84 receptor during GVHD induction can significantly affect the host Th1/Th2 balance. And, by assessing this parameter, the direction of development and the intensity of the pathological process can be determined. The aim of this work was to investigate the effect of ligands such as medium-chain fatty acid receptor GPR84 on the Th1/Th2 balance in an experimental model in an in vivo system.

Female DBA/2 and hybrids (C57Bl/6 × DBA/2) F1 mouse strains were used in the experiments.The studied ligands of GPR84 were capric and lauric acids, as well as a synthetic ligand 6-OAU. Chronic GVHD in the semi-allogenic system was induced by injecting splenocytes from DBA/2 mice to B6D2F1 hybrid mice: 60-70 × 106 -cells iv twice with an interval of 6 days. The first administration of the GPR84 ligands was performed one hour after the donor cell transfer and then once a day for two weeks.The effect of the study drugs on the course of chronic GVHD was assessed three months after the onset of the experiment.

It was shown that the administration of GPR84 ligands to to animals during the induction of chronic GVHD affects the activity of the receptor and the host Th1/Th2 ratio. In the group with the injection of 6-OAU, the number of animals which the immunopathological process developed according to the Th1-dependent variant increased by more than 1.5-fold, compared with the control group. This fact is consistent with the literature data obtained in the in vitro system. Apparently, the effect of a mixture of capric and lauric acids is mediated by some other mechanism, differed from the GPR84 activation. Therefore, further research is required to realize the promising possibility of adjusting immune responses by including certain fatty acids in the diet.
HEPATIC SOD1 GENE EXPRESSION CHANGES IN THE NAFLD PATHOGENESIS IN OBESITY
Authors: Komar A. A. , Shunkina (Skuratovsvkaia) D. A. , Vulf M. A. , Vu H. Q. , Todosenko N. M. , Zatolokin P. A. , Kirienkova E. V. , Gazatova N. D. , Litvinova L. S.
Published: October 2021

Steatosis in the liver in obesity increases the work of mitochondria to utilize excess lipids. An overload of β-oxidation of fatty acids, the tricarboxylic acid cycle, and oxidative phosphorylation leads to a decrease in ATP and an increase in the formation of reactive oxygen species. Normally, mitochondria can efficiently remove elevated levels of reactive oxygen species using the cell's antioxidant system and metabolic adaptation to altered conditions. This study aimed to investigate the role of hepatic SOD expression in the pathogenesis of NAFLD in obesity. It was found that the level of SOD1 expression in the liver in obese patients with and without type 2 diabetes with a BMI > 40 kg/m2 was lower than in healthy donors. The copy number of mitochondrial DNA (mtDNA) in the liver in all obese patients was more than two times lower than in the control group. In the liver of obese patients without type 2 diabetes, the SOD1 protein level and the mtDNA copy number were interrelated and negatively correlated with the area of fatty inclusions. Thus, in obese patients, a decrease in antioxidant defense in the liver leads to the vulnerability of mitochondria, which, in turn, contributes to the progression of steatosis and insulin resistance.
INVESTIGATION OF BLOOD MONONUCLEAR CELLS CYTOKINE-PRODUCTION FUNCTION FROM PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH THE ENDOGENOUS RETROVIRUS HERV-E λ 4-1 CONSERVATIVE REGION SYNTHETIC OLIGOPEPTIDE
Authors: Goldina I. A. , Markova E. V.
Published: October 2021

Considering to the data of class I human endogenous retrovirus HERV-Е λ 4-1 subgroup association with multiple sclerosis, an autoimmune disease accompanied by neuroinflammation, changes in the neurotransmitters level, progressive neurological dysfunction, as well as the ability of this retrovirus to replicate and to produce proteins with potential immunomodulatory properties, the aim of this work was a comparative study of the blood immune cells cytokine synthesizing function in conventionally healthy individuals and multiple sclerosis patients under the synthetic 17 – amino acid oligopeptide homologous to the hydrophobic transmembrane protein р15Е HERV-Е λ 4-1 conserved region influence. The 40 patients, 17 male persons aged 38.0 (31.0-47.0) years old and 23 female persons aged 39.0 (31.0-50.0) years old with an established diagnosis of multiple sclerosis (G 35, ICD-10), corresponding to the McDonald 2005, modified in 2010 criteria with a continuously progressive disease course and the disease duration of 17.0 (14.0-18.0) years, and 30 conditionally healthy individuals, 12 male persons aged 32.0 (23.0-43.0) years old and 18 female persons aged 36.0 (29.0-46.0) years old were the objects of the study. An open-label, observational, single-center, cohort, controlled, randomized trial was conducted. It was found that the donor’s blood mononuclear cells IL-1β, IL-6, TNFα, IFNγ and IL-2 spontaneous production in culture was stimulated, but that of IL-4 and IL-10 did not change under the retroviral oligopeptide influence. At the same time, the spontaneous and mitogenstimulated production of all studied cytokines did not change under the control oligopeptide influence. The PHA-stimulated donor’s blood mononuclear cells cultivation in presence of the retroviral oligopeptide, as compared to the control one, was accompanied by an increase in the IL-1β, IL-6 and TNFα release into the culture supernatant. The multiple sclerosis patients were characterized by IL-1β, IL-6 and IFNγ higher content in the mitogen-unstimulated blood mononuclear cells culture supernatant, compared with conditionally healthy individuals, as well as by a higher production of IL-6 and IFNγ in response to PHA stimulation. The retroviral oligopeptide, in contrast to the control one, stimulated the IL-1β, IL-6, TNFα and IFNγ spontaneous production without altering that of IL-4 and IL-10 in multiple sclerosis patients. The obtained results indicate that the synthetic oligopeptide homologous to the conserved region of the hydrophobic transmembrane protein p15E HERV-Е λ 4-1 has the pro-inflammatory properties, which is probably the one of human endogenous retrovirus HERV-Е λ 4-1 pathological abilities realization mechanism in multiple sclerosis.
INFLUENCE OF HOMEOSTATIC CYTOKINES – IL-7 AND IL-15 ON T-REGULATORY CELLS IN VITRO
Authors: Shevyrev D. V. , Kozlov V. A.
Published: October 2021

Cytokines IL-7 and IL-15 are the most important humoral factors providing T-conventional cell pool reconstitution during homeostatic proliferation caused by lymphopenia. However, whether these cytokines can provide homeostatic maintenance and proliferation of T-regulatory (Treg) cells is largely unknown. Considering the association between homeostatic proliferation and the development of autoimmunity, we decided to investigate the ability of these factors to cause differentiation of Treg-cells into Th17-lymphocytes. Therefore, the purpose of this study was to investigate the influence of humoral factors of homeostatic proliferation (IL-7 and IL-15) on Treg-cells in vitro. The study used peripheral blood sampled from 22 healthy donors. PBMC fraction was isolated by Ficoll density gradient centrifugation. Proliferation was induced by IL-7, IL-15, and by a combination of IL-2 with anti-CD3-antibodies. The proliferation intensity of Tregs was evaluated by flow cytometry using CFSE in PBMC cultures by phenotype CD3+CD4+CD25+FoxP3+ and in the previously purified population of CD3+CD4+CD25+CD127lo-cells. In this case Treg-cells were obtained by immunomagnetic separation from PBMCs using a MACS Treg Isolation Kit. Also, the RORyt expression in CD3+CD4+CD25+FoxP3+-cells was evaluated during cultivation. Here, we have shown that IL-7 and IL-15 could support Treg-cells by number and phenotype. Also, we revealed that these factors provide FoxP3 expression in Treg-cells; meanwhile, stimulation with IL-2 + anti-CD3 can also cause induction of FoxP3 expression de novo in conventional CD4+ cells. Also, we have shown that IL-7 and IL-15 can cause lower-intensity proliferation of Treg-cells in comparison with IL-2 + anti-CD3. Herewith homeostatic cytokines didn’t have the ability to induce RORyt expression in both T-regulatory cells and CD4+ conventional T-lymphocytes. Thus, it has been shown that IL-7 and IL-15 can potentially participate in maintaining the total pool of Treg-cells during lymphopenia, when IL-2 deficiency occurs, without causing the induction of RORyt expression. However, how homeostatic cytokines affect the functional activity of Treg-cells remains unclear and requires further investigation.
INFLUENCE OF RENAL DYSFUNCTION ON THE LEVEL OF SERUM ANGIOPOIETIN-LIKE PROTEINS AND ANTI-PHOSPHOLIPID ANTIBODIES IN PATIENTS WITH RHEUMATOID ARTHRITIS AND METABOLIC SYNDROME
Authors: Aleksandrov V. A. , Shilova L. N. , Aleksandrov A. V. , Aleksandrova N. V. , Zborovskaya I. A.
Published: October 2021

Rheumatoid arthritis (RA) is a frequent background for the development of renal pathology. Chronic kidney disease (CKD) is determined in more than 30% of patients with RA. Along with inflammation and other factors in the progression of the underlying disease, the development of renal damage in RA is facilitated by the presence of metabolic syndrome (MetS).

The aim of this study is to assess the relationship of serum concentrations of angiopoietin-like proteins (ANGPTL) and antiphospholipid antibodies (aPL) with the development of renal dysfunction in patients with RA.

We examined 158 patients with RA (91.8% – women and 8.2% – men) aged 21 to 80 years old and an average duration of the disease – 9 (4-15) years. The majority of patients were seropositive for rheumatoid factor and for antibodies to cyclic citrullinated peptide, with an advanced clinical stage and moderate activity (3.2 < DAS28 ≤ 5.1) of the pathological process.

The ELISA test was used for the quantitative determination of angiopoietin-like protein type 3 and type 4 and antibodies to phospholipids (aРL-IgG/IgM) for total detection of antibodies to cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylic acid and a complex of negatively charged phospholipid and β2-glycoprotein-I.

More than half of the examined RA patients had the calculated glomerular filtration rate (eGFR) ranging from 89 to 60 ml/min/1.73 m2 (allocation by CKD stages: C1 – 21.5%; C2 – 58.9%; C3 – 19.6%). Signs of MetS (a combination of increased blood pressure, increased triglyceride levels and carbohydrate metabolism disorders against the background of central obesity) were diagnosed in 68 (43%) RA patients. Multivariable analysis of variance was performed to compare the studied parameters (ANGPTL3, ANGPTL4, aPL) depending on eGFR in groups of RA patients without signs of metabolic syndrome and RA patients with MetS. Significant differences in the level of ANGPTL3 (F = 8.86, p = 0.0034) and ANGPTL4 (F = 29.6, p < 0.001), but not aPL (p > 0,05) were found between RA patients with varying degrees of severity of metabolic disorders.

Multivariable analysis of variance showed a significant increase in ANGPTL4 in the blood serum of RA patients with reduced eGFR (< 89 ml/min) (F = 18.5, p < 0.001) and pronounced metabolic changes (F = 24.2, p < 0.001). Thus, only two factors (renal dysfunction and the presence of MetS) had a direct effect on the ANGPTL4 content in RA patients, which could describe the variability of this sign in more than 30% of cases. The squared multiple correlation coefficient (R2 ) in this model was 0.33. ANGPTL type 4 should be considered as a key factor linking the development of renal dysfunction and metabolic changes caused by rheumatoid inflammation.
PENTOXIFYLLINE ENHANCES IN VITRO T-CELL ANTITUMOR RESPONSE IN BREAST CANCER PATIENTS
Authors: Kuznetsova M. S. , Shevchenko J. A. , Khantakova J. N. , Khristin A. A. , Obleukhova I. A. , Silkov A. N. , Sidorov S. V. , Sennikov S. V.
Published: October 2021

The NF-κB transcription factor controls the expression of genes responsible for cell cycle, apoptosis, and other immunoregulatory functions. Some nonspecific NF-κB inhibitors were found after discovering the possibility of blocking tumor growth through suppression of NF-κB activity, but their use was complicated by multiple side effects, such as interleukin-1β-related systemic inflammation or non-immunerelated complications, which may be due to inhibition of the p65 NF-κB subunit that plays a central role in organogenesis and inflammation. Inhibition of the c-Rel subunit leads to tumor growth restriction by modulating the T-regulatory cell activity.

In 2017, Grinberg-Bleyer and co-authors checked the hypothesis that selective inhibition of the c-Rel subunit can be performed using pentoxifylline and will effectively regulate Treg activity during tumor growth. The authors showed that pentoxphylline, an FDA-approved drug, could indeed induce selective degradation of c-Rel without affecting p65, and suggested that such an effect could be effective in suppressing tumor growth. In this regard, we aimed to investigate in vitro how pentoxifylline affect the functional activity and antitumor cytotoxic potential of T-cells in cancer patients.

The objects of the study were peripheral blood mononuclear cells from 25 patients with primary breast cancer (no metastases), 15 patients with metastatic breast cancer, and 25 healthy women without breast pathology. Informed consent was obtained from all donors and patients. The study was approved by the local ethics committee.

Here we showed that pentoxifylline treatment in vitro enhances the pro-apoptotic and cytotoxic antitumor response via increasing the expression of TRAIL on T-lymphocytes, mainly in healthy donors and patients with metastatic breast cancer, both on intact T-cells and in response to the cells of the tumor line of human breast carcinoma ZR-75-1. In healthy donors, in the presence of pentoxifylline, a population of highly expressing TRAIL CD4 and CD8 T-cells appears.
REGULATION OF PERIPHERAL B-LYMPHOCYTE DIFFERENTIATION IN RECURRENT MISCARRIAGE
Authors: Malyshkina A. I. , Sotnikova N. Yu. , Kust A. V. , Voronin D. N.
Published: October 2021

The important role of immune disorders in recurrent miscarriage has been proven. Clarification of the character of B-lymphocyte differentiation and its regulation factors in women with threatened miscarriage and recurrent miscarriage in history is an urgent problem, since it will reveal the immune mechanisms of the pathogenesis of this pathology. Purpose: to establish the features of B-lymphocyte differentiation and factors of its regulation in women with a history of recurrent miscarriage and threatening spontaneous miscarriage at the time of examination.

Were examined pregnant women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 60 pregnant women with a threatening spontaneous miscarriage at the time of examination and a history of recurrent miscarriage. As a control, 35 pregnant women with uncomplicated pregnancy were examined. The comparison group consisted of 25 primary pregnant women with threatened spontaneous miscarriage at the time of examination. The material for the study was peripheral venous blood. Subpopulations of B-lymphocytes CD19+, CD19+ IgD+, CD20+IgM+, CD20+IgG+ were determined by flow cytometry; CD19+CD20- CD38+, CD19+CD27- , CD19+CD27+. Serum levels of BAFF and APRIL were assessed by enzyme-linked immunosorbent assay.

In the main group, an increase in the proportion of B-cells, CD20+IgM+-lymphocytes and memory cells was recorded in the peripheral blood, along with a decrease in the level of naive cells and plasma cells. In the comparison group, an increase in the proportion of immature IgM+B-cells, circulating memory cells, along with a decrease in naive B-lymphocytes, was registered. in the main group there was a pronounced decrease in the serum BAFF level compared with the control and comparison groups. Analysis of the APRIL content showed a pronounced downward trend in groups with threatened miscarriage relative to healthy pregnant women. Thus, threatening habitual and sporadic miscarriages were associated with a shift in the differentiation of B-lymphocytes towards immature forms and a lack of regulatory influence of BAFF and APRIL, which is reflected in the disruption of B-cell homeostasis and weakening of humoral effector mechanisms at the systemic level. The revealed changes may indicate a single mechanism for the development of a threatening spontaneous miscarriage, the severity of which increases with repeated loss of pregnancy. These changes can lead to an increase in effector cytotoxic mechanisms and an increase in proinflammatory cytokines, which can lead to the development of damaging reactions in the fetoplacental complex, which can be reflected in the clinical picture of the threat of termination of pregnancy.
Methods of carotid endarterectomy
Authors: Kazantsev A. N. , Vinogradov R. A. , Chernykh K. P. , Dzhanelidze M. O. , Bagdavadze G. Sh. , Artyukhov S. V. , Chikin A. E. , Linets Yu. P.
Published: October 2021

This literature review is devoted to various carotid endarterectomy (CE) methods that exist today in Russia. The pros and cons of conventional and eversion technique of the operation are given. It is indicated that the former is associated with higher long-term rate of restenosis, aneurysm and patch infection. The second is associated with higher prevalence of intraoperative internal carotid artery (ICA) thrombosis due to intimal detachment distal to endarterectomy area. The following CE methods for patients with prolonged ICA involvement are described: neo bifurcation formation, autoarterial reconstruction, ICA autotransplantation, plastic using an occipital artery flap. The methods of CE with carotid body saving have been demonstrated: 1. Swallow tail type patch repair proposed by R.I. Izhbuldin; 2. S-shaped arteriotomy proposed by K. A. Antsupov; 3. Two types of operations proposed by R. А. Vinogradov; 4. Сutting off the ICA with sections of common and external carotid artery proposed by A. N. Kazantsev; 5. Glomus-saving ICA autotransplantation in patients with prolonged atherosclerotic involvement. The role of ICA transposition over the hypoglossal nerve in eversion CE is presented. The glomus-saving CE with ICA transposition, called Chik-Chirik CE, is described. Conclusions are drawn on the need to demonstrate all CE types in the novel Russian guidelines for the management of patients with of head and neck arterial diseases.
Diagnostic value of electrocardiographic markers of left bundle branch block in predicting left ventricular reverse remodeling in patients receiving cardiac resynchronization therapy
Authors: Malishevsky L. M. , Kuznetsov V. A. , Todosiychuk V. V. , Shirokov N. E. , Lebedev D. S.
Published: October 2021

Aim. To analyze the prognostic value of 18 electrocardiographic (ECG) markers of left bundle branch block (LBBB) in predicting left ventricular (LV) reverse remodeling in patients receiving cardiac resynchronization therapy (CRT).

Material and methods. The study included 98 patients. Depending on the presence of reverse remodeling during CRT, defined as a decrease in LV endsystolic volume ≥15%, the patients were divided into two groups: non-responders (n=33) and responders (n=65). We selected and analyzed 18 ECG markers included in 9 LBBB criteria.

Results. Among the ECG markers significantly associated with reverse remodeling during CRT, the absence of q wave in leads V5-V6 demonstrated the highest sensitivity (92,31%), a negative predictive value (70,59%) and overall accuracy (73,47%). Normal internal deviation interval of the R wave in leads V1-V3 was also associated with the best sensitivity (92.31%), while QS with a positive T in lead aVR — the best specificity (69,7%). Discordant T wave demonstrated the highest positive predictive value (80,33%). Multivariate analysis revealed following ECG signs independently associated with reverse remodeling during CRT: QRS complex duration (odds ratio (OR)=1,022; 95% confidence interval (CI): 1,001-1,043; p=0,040); absence of q wave in leads V5-V6 (OR=4,076; 95% CI: 1,071-15,51; p=0,039); discordant T wave (OR=4,565; 95% CI: 1,708-12,202; p=0,002). These ECG findings were combined into a mathematical model that demonstrated high predictive power (AUC=0,81 [0,722-0,898], p<0,001). Once the cut-off point was determined, a binary variable was obtained that showed higher sensitivity, negative predictive value, and overall accuracy when compared with the actual LBBB criteria. The 5-year survival rate among patients with a model value above the cut-off point was 84,4%, while in patients with a value below the cut-off point — 50% (Log-rank test, p=0,001). To improve usability of the model, a mobile application was developed.

Conclusion. For the first time, the diagnostic value of ECG markers of LBBB were analyzed and a mathematical model with ECG signs was proposed to predict reverse remodeling in patients receiving CRT.