bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of phenotypic properties of innate lymphoid cells at various stages of rheumatoid arthritis
Authors: Boeva O. S. , Kozlov V. A. , Sizikov A. E. , Korolev M. A. , Chumasova O. A. , Omelchenko V. O. , Kurochkina Yu. D. , Pashkina E. A.
Published: June 2023

Autoimmune diseases currently take a leading place in terms of frequency of occurrence in the population, among which 1 percent is occupied by rheumatoid arthritis (RA). Remission in this type of disease is extremely rare and requires constant use of pharmacotherapy. Studying the pathogenesis of RA is necessary to study to search for new drug targets. It is known that T helpers 1 (Th) and Th17 are involved in the development of RA. However, some researchers suggest that ILCs play a role in the development of RA. ILCs are “innate analogues” of Th, due to the fact that this subpopulation synthesizes the same cytokines. ILC1 is innate analogs of Th1, ILC2-Th2, ILC3-Th17. ILCs are tissue-resident innate lymphoid cells that have functional diversity and regulate the direction of the immune response through the production of cytokines.

We used peripheral blood mononuclear cells (PBMCs) from patients (n = 19) and conditionally healthy donors (n = 10) as material. The group of patients was divided biologic disease-modifying anti-rheumatic drugs (bDMARDs) and Metotrexate (MTX) and of stage of RA (early and very early arthritis, advanced and late). PBMCs were stained with monoclonal antibodies. ILCs were identified as Lin-CD127+, CD294+ILCs (ILC2) were measured in the general population, CD117-CD294-ILCs were identified as ILC1, and CD117+CD294-ILCs were identified as ILC3.

We obtained the following results: ILC1 was significantly reduced in patients treated with MTX comparison with patients on bDMARDs and healthy donors. However, patients on MTX with advanced RA had low levels of ILC2 and ILC3 compared to patients on bDMARDs. ILC2 significantly increased in patients with early stages of RA comparison with patients with advanced RA. However, ILC1 was significantly reduced in patients treated with MTX, and ILC3 increased significantly in patients treated with MTX comparison with bDMARDs. Expression of PD1 on ILC1 was increased compared to patients treated with bDMARDs. However, ILC3 patients with advanced stages on MTX had increased expression of PD1 comparison with patients taking bDMARDs. The ILC3 of donors was significantly increased comparison with patients on bDMARDs.
Characteristics of T-cell immunity and level of the natural killer cells content in COVID-19 convalescents with carbohydrate metabolism disorders
Authors: Savchuk K. S.
Published: June 2023

The pandemic of the new COVID-19 coronavirus infection has created a public health emergency in the Russian Federation in 2020-2022. COVID-19 causes various consequences, often manifested by the endocrine system dysfunction. The rationale for our study is insufficient data on T and NK cell immunity in patients with hyperglycemia after COVID-19. The study was aimed at the features of T cell immunity in individuals with post-COVID syndrome and disorders of carbohydrate metabolism, depending on the NK cells count. Materials and methods: Sixty-four post-COVID patients with carbohydrate metabolism disorders were divided into three groups: with reduced, normal, or elevated NK cell counts. Carbohydrate metabolism disorders included impaired glucose tolerance (n = 36) and type 2 diabetes mellitus (n = 28). The comparison group comprised 60 post-COVID persons with no history of carbohydrate metabolism disorders. The assessment of the lymphocytic link of immunity included the definition of: CD45+CD3+ (T lymphocytes), CD45+CD3+CD4+ (T helpers), CD45+CD3+CD8+ (T cytotoxic), CD45+CD3+CD16+CD56+ (T-NK cells), CD45+CD3-CD16+CD56+ (natural killers), CD45+CD3+CD4+CD25+ (T lymphocytes – early activation), CD45+CD3+HLA-DR+ (T lymphocytes – late activation). Results and Discussion. As the study showed, a decrease in the number of natural killers was accompanied by a higher level of T helpers in the group with carbohydrate metabolism disorders, the latter is probably associated with a compensatory increase in T lymphocytes and dysregulation of the T cell link of the immune system. It can also be concluded that in patients with long-COVID and CMD, with normal NK cell counts, an altered subpopulation composition remains, namely, a significant increase in total T lymphocytes. Many authors associate the obtained data on a significant decrease in T-NK lymphocytes with a decrease in the antiviral activity of the immune system, which can lead to a poor response to new viral agents or contribute to the activation of chronic viral infections. Dysregulation of the T cell link in individuals with long-COVID and disorders of carbohydrate metabolism requires a more detailed study, including an assessment of the cytokine profile in this category of patients.
Diagnostically significant changes in subsets CD11b+CD64-CD32+CD16+, CD11b+CD64+CD32+CD16+ neutrophilic granulocytes of immunocompromised women with chronic infectious and inflammatory diseases of the genital tract of various etiologies
Authors: Kovaleva S. V. , Nesterova I. V. , Pikturno S. N. , Dydyshko E. I. , Prosolypova N. S. , Chulkova А. M.
Published: June 2023

Chronic pelvic inflammatory disease (PID) in women remains a problem due to the importance of medical consequences. The study of the receptor apparatus of neutrophilic granulocytes (NG) involved in anti-infective protection in diseases of various etiologies seems to be relevant. Aim: to clarify the features of variants of quantitative and phenotypic changes in subsets of NG CD11b+CD64-CD32+CD16+, CD11b+CD64+CD32+CD16+ of immunocompromised women during exacerbation of chronic PID of various etiologies. We were tested women 20-40 years: Study Group 1 (SG1, n = 20) – chronic PID during the exacerbation with mono- or mixed latent/recurrent various viral infections (chronic herpes-virus infections, papillomavirus infection, recurrent ARVI); Study Group 2 (SG2, n = 30) – chronic PID of bacterial etiologies; Comparison Group (CG)– 20 healthy women. The number of subsets CD11b+CD64-CD32+CD16+NG (major) and CD11b+CD64+CD32+CD16+NG (minor), receptor expression density (MFI) was determined (FC500, USA). It was found that in PID during the period of exacerbation, diagnostically significant differences in the subset composition of NG were revealed. We got a decrease in the CD11b+СD64-СD32+СD16+NG subset and in 7,6 times increase in the CD11b+CD64+CD32+CD16+NG subset in SG2 with chronic PID of bacterial etiology, in contrast to chronic PID occurring in combination with recurrent/persistent viral infection SG1. Negative transformation of NG subsets is associated with a predominant decrease in the level of expression of the activation CD16. The absence of an adequate response to the infectious and inflammatory process was revealed – the absence of an increase in the expression of the activation CD11b in the major subset in SG1, as well as in the minor subset in groups SG1 and SG2. In the major subset of NG in groups SG2 a decrease in the expression of the activation marker CD11b. In the various viral infections and PID (SG1), in the negatively altered minor subset of NG we got a decrease of expression of CD16, an increase of expression of CD64 and CD32. Determination of subsets of CD11b+СD64-СD32+СD16+, CD11b+CD64+CD32+CD16+NG and their phenotype can be used as diagnostic markers for the differential diagnosis of PID of viral and bacterial etiology, and for the development of new methods of targeted immunomodulatory therapy.
Features of the frequency of occurrence of T-330G IL2 gene polymorphism in patients with COVID-19
Authors: Ageeva E. S. , Ablaeva R. N. , Yatskov I. A. , Aleshina O. K. , Rymarenko N. V. , Beloglazov V. A. , Dyadyura E. N.
Published: June 2023

SARS-CoV-2 infection is the etiopathogenetic factor of the new coronavirus infection. Susceptibility to the virus and, accordingly, the incidence differs in children and adults. On the one hand, this reflects the age-related features of the immune response. On the other hand, it is realized through the production of a number of cytokines, including IL-2, and reflects the genetically determined features of cytokine production. The aim of the study was to analyze the frequency of occurrence of T-330G polymorphic variants of the IL2 gene in patients with a new coronavirus infection. A total of 145 patients were examined, including 31.0% of children (n = 45) and 69.0% of adults (n = 100). The diagnosis of a new coronavirus infection was verified by RT-PCR confirming the presence of the SARS-CoV-2 virus and identifying clinical symptoms of an upper respiratory tract infection. The control group consisted of 50 healthy volunteer donors. Allele-specific PCR with electrophoretic detection in 3% agarose gel (Litech, Russia) was used to analyze the T-330G polymorphism of the IL2 gene. To compare the frequencies of allele combinations, the χ2 test and the odds ratio OR and (95% CI) were used.

The dominant genotype in patients with COVID-19 was the heterozygous GT genotype of the T-330G polymorphism of the IL2 gene. In the group of children at risk of developing a new coronavirus infection, the GG genotype of the T-330G polymorphism of the IL2 gene was associated (31.1% in children and 18.0% in the control group, p < 0.05, OR = 2.047). While the homozygous TT genotype of the T-330G polymorphism of the IL2 gene was a protective genotype (its occurrence rate was 26.7% in patients, 54.0% in the control group, p < 0.05, OR = 0.315). In adults, the heterozygous GT genotype of the T-330G polymorphism of the IL2 gene was associated with the risk of developing a new coronavirus infection (in the group of patients – 44.0% versus control – 28.0%, p = 0.028, OR = 2.020). A low risk of developing the disease was associated with the homozygous TT variant of the T-330G polymorphism of the IL2 gene (in the group of patients 37.0% versus control – 54.0%, p = 0.024, OR = 0.500).

The T-330G polymorphism of the promoter zone of the IL2 gene differently affects its production. The direction of the immune response and its effectiveness depend on the level of IL-2. Understanding the individual factors that determine the features of the immune response can help in understanding the mechanisms of development of COVID-19-associated diseases and the selection of approaches to personalized methods of their treatment.
Features of the immune status of patients with acute coronary syndrome who underwent СOVID-19, depending on the number of cytotoxic T lymphocytes (CD8+)
Authors: Safronova E. A. , Ryabova L. V. , Zurochka A. V.
Published: June 2023

The 2019 coronavirus disease (COVID-19) pandemic has had an unprecedented impact on health and economies around the world. Direct myocardial injury and cytokine storm, leading to destabilization of preexisting plaques and accelerated formation of new plaques, are two mechanisms that trigger the acute coronary syndrome in COVID-19. There is insufficient data on the immune status of patients with acute coronary syndrome who have undergone COVID-19. The aim of the study was to study T and B cell, humoral immunity depending on the number of cytotoxic T lymphocytes (CD8+) in patients with acute coronary syndrome who underwent COVID-19. Materials and methods of research: 65 men with unstable angina pectoris and acute myocardial infarction (acute coronary syndrome) from 40 to 65 years old, who had previously had COVID-19, were examined. A study of peripheral blood was carried out: complete blood count (Medonic device, Sweden), general and specific IgM, IgG, IgA, compliment fragments (Vector Best, Russia). Subpopulations of T and B lymphocytes were determined by flow cytometry. In persons with acute coronary syndrome who underwent COVID-19 with predominantly normal and elevated levels of cytotoxic T cells, a more severe course of the disease was observed: patients with acute myocardial infarction prevailed, they had longer mortality, longer treatment duration, and stent thrombosis was more common. In patients with elevated cytotoxic T cells, there was a maximum increase in erythrocytes, hemoglobin, hematocrit, lymphocytes of both the total number and subpopulations – T helpers, T-NK lymphocytes, NK lymphocytes, T lymphocytes of early and late activation, B1 and B2 lymphocytes, index of NBT-induced test. In patients with normal levels of NK cells, compared with other groups, there was an increase in spontaneous NBT activity and index, a significant decrease in C3a and C5a complement fragments. Prevalence of stent thrombosis and mortality in the group of patients with normal levels of cytotoxic T cells may indicate torpidity of the immune system in these patients with poor outcomes.
Interplay between copper and cobalt in hematopoiesis and the impact of their deficiency on anemia development
Authors: Jiemuratova G. K.
Published: June 2023

Hematopoiesis is a complex process that requires a specific set of blood components to function properly. Blood diseases can result from imbalances or deficiencies in these components. The body has physiological sensors that respond to environmental changes by maintaining elemental homeostasis. A deficiency in one micronutrient can lead to imbalances in others. The purpose of this study was to investigate the role and interaction of copper, cobalt, and iron in hematopoiesis and to determine the prevalence of anemia in children living in the Aral Sea region.

A total of 1120 children and adolescents were examined, and their physical development was measured using anthropometric measurements and laboratory tests. Hair samples were analyzed to determine the children's micronutrient status. The results revealed that 78% of the children had a decrease in hemoglobin, and anemia was more prevalent in adolescents. A correlation was found between high growth and increased levels of erythrocytes and hemoglobin. The study also identified the most common hypomicroelementoses in the Aral Sea region, including copper deficiency in 98.4% of cases, cobalt deficiency in 92.1%, and zinc deficiency in 57.8%.

The study also analyzed the ratio of trace elements, revealing an increased Fe/Cu and Fe/Cu ratio in all age groups. Imbalances and deficiencies in copper, cobalt, zinc, and manganese were found to contribute to the development of anemia in children. Hair analysis for trace elements was shown to be significant in the differential diagnosis and treatment of children with anemia.

In conclusion, the study highlights the importance of maintaining a proper balance of trace elements in hematopoiesis. Deficiencies in copper, cobalt, zinc, and manganese can contribute to anemia in children, and hair analysis can be used to diagnose and treat the condition. Further research is needed to better understand the role of trace elements in hematopoiesis and their impact on human health.
In HIV-infected patients, intestinal bacteria-derived products interfere with CD4+T cell regeneration
Authors: Korolevskaya L. B. , Saidakova E. V. , Shmagel N. G. , Shmagel K. V.
Published: June 2023

Despite successful suppression of viral replication by antiretroviral drugs there is no significant increase in the number of peripheral CD4+T lymphocytes in some HIV-infected patients (immune nonresponse to therapy). One of the crucial factors for immunodeficiency aggravation is immune activation developing in response to the bacterial products entry into the bloodstream through the damaged intestinal barrier. Additionally, the intestinal microflora produces various solutes that accumulate in the blood and exhibit toxic properties. This work aimed to evaluate the effect of intestinal microbial products (para-cresol sulfate and indoxyl sulfate) on the number of CD4+T lymphocytes in HIV-infected patients receiving antiretroviral therapy. The object of the study was the peripheral blood of HIV-infected subjects with different immune system restoration efficiency during the therapy. Uninfected donors were enrolled as healthy controls. Plasma concentrations of IL-6 (p = 0.012), IP-10 (p = 0.0004), and sCD14 (p = 0.003) in HIV-infected immune nonresponders were increased compared with those in individuals with effective restoration of CD4+Tcells (immune responders). Although both groups of HIV-positive subjects did not differ in plasma lipopolysaccharide and I-FABP levels, para-cresol sulfate (p = 0.001) and indoxyl sulfate (p = 0.042) concentrations were increased in immune non-responders. In vitro experiments showed a negative dose-dependent effect of para-cresol sulfate and indoxyl sulfate on the viability and mitotic activity of CD4+T lymphocytes. Thus, in HIV-infected patients with impaired regeneration of CD4+T lymphocytes during antiretroviral therapy, a higher level of systemic inflammation is noted than in subjects responding to treatment with an increase in the number of CD4+T cells. The severity of the intestinal barrier damage and the load of bacterial components released into the bloodstream are approximately the same in HIV-infected individuals with different efficiency of immune recovery in response to treatment. Simultaneously, the blood plasma of immune non-responders is significantly enriched with microbial products of intestinal origin: para-cresol sulfate and indoxyl sulfate. The significant decrease in the proliferative capacity of CD4+T cells stimulated in vitro and the induction of their death in the presence of these toxins may be a reason for the ineffective restoration of the number of CD4+T lymphocytes in HIV-infected individuals receiving antiretroviral therapy.
Identification of the relationship between biomarkers of autophagy, apoptosis and inflammation in the acute period of atherothrombotic ischemic stroke
Authors: Lugovaya A. V. , Kalinina N. M. , Ivanov A. M. , Nikitin Yu. V. , Sukhina I. А. , Mitreikin V. F. , Semenova E. V.
Published: June 2023

The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response.
Local cytokine levels as prognostic factors for early relapse of non-muscle-invasive bladder carcinoma
Authors: Zlatnik E. Yu. , Sagakyants A. B. , Shulgina O. G. , Shevchenko A. N. , Filatova E. V. , Belyakova L. I. , Breus A. A. , Maslov A. A. , Maslov A. A. , Rozenko L. Ya.
Published: June 2023

The aim of our study is to assess the local cytokine levels as prognostic factors for early relapse in NMIBC patients. 75 patients with NMIBC were enrolled in the study: 51 with primary NMIBC and 24 with initially recurrent NMIBC, LG and HG tumors were diagnosed in each group. Patients with primary NMIBC were monitored during 9 months after treatment: TURB and chemotherapy (No. 6). During TURB samples of tumors were taken, supernatants were obtained and tissue cytokine levels were measured (IL-1β, IL-6, IL-10, IL-18, TNFα, IFNγ, IL-8) by ELISA test. The results showed that in patients with primary NMIBC early relapses were diagnosed in 15 (46.8%) of LG tumors and in 11 (45%) of HG tumors matching that there was no difference depending upon tumor grade. In initially recurrent tumors of both LG and HG NMIBC the amounts of cytokines were maximal: in LG tumors they exceeded the primary ones from 7.1 (IFNγ) to 300 (IL-6) while in HG - from 2.0 (IL-10) to 9.7 (IL-6). The amounts of IL-1β, IL-6, IL-10, IFNγ, IL-8 were higher in those LG primary tumors which relapsed in 6-9 months compared to the ones which didn't, though their levels were much lower than in initially manifested relapse (from 2.6 times for IFNy to 150 times for IL-6). A similar trend, though not for all the same cytokines, was observed in HG tumors: tissue levels of IL-6, IL-10, IL-18 and TNFα were higher in tumors which relapsed in 6-9 months after treatment. The increase of 2 cytokines' levels were common for both LG and HG tumors (IL-6 and IL-10). This finding might be considered as a new prognostic factor of the early relapse. We conclude that relapse of LG and HG NMIBC is related to some immune mechanisms, namely to local hyperproduction of cytokines, especially IL-6 and IL-10, though IL-1β, IL-8, IFNγ could have an impact on LG and IL-18, TNFα — on HG tumors. Taking into account common signaling pathways of IL-6 and IL-10 like JAK/STAT, these transcription factors might be potential targets for new effective approaches to treatment.
Metalloproteinase 9 and its role in the pathogenesis of allergic diseases in children
Authors: Semernik O. E. , Lebedenko A. A. , Appoeva A. A.
Published: June 2023

Metalloproteinases (MMP) play a significant role in the mechanisms of maintaining chronic inflammation and tissue remodeling. The study of concentration changes in these enzymes in the blood serum of children with allergopathology is of great practical and scientific interest.

Objective: to study the role of MMP-9 in the pathogenesis of allergic diseases in children. 180 children aged from 1 to 18 years passed a comprehensive clinical and laboratory examination. This study included patients suffering from bronchial asthma (BA) (n = 54), atopic dermatitis (AD) (n = 54) and combination of these pathologies (n = 72). Serum levels of MMP9 were determined by enzyme immunoassay using Cloud-CloneCorp® test systems (USA).

The analysis of the obtained data showed that among patients with the established diagnosis of BA, the maximum concentration of this cytokine was registered in children with a moderate course of the disease. The conducted correlation analysis showed the presence of a significant correlation between the severity of asthma and the level of control over the disease (r = 0.63). Similar data was obtained in patients with a combination of BA and AD. In children of this group, there was also a significant increase in serum MMP-9 compared with healthy patients (p = 0.015). The concentration of this matrix metalloproteinase in serum was slightly higher among children with polyvalent sensitization than in patients with monoallergic etiology of the disease (p = 0.272). The values of MMP-9 in patients with only skin manifestations of atopy were significantly higher than in the control group (p = 0.025).

The data we obtained showed that all the patients we examined had a significant increase in the level of MMP-9 in the blood serum, which indicates an important role of this cytokine in the pathogenesis of allergic diseases in children.
Proinflammatory cytokines VEGFA, IL-6, IL-8 as markers of hepatotoxicity after COVID-19
Authors: Urevskii M. A. , Ilmukhina L. V. , Saranskaya Ya. E. , Lapshin A. A. , Gafurova R. R.
Published: June 2023

The mechanism of hepatocellular liver damage after COVID-19 is a multifactorial process. The most widely discussed causes are cytolytic liver damage due to the inflammatory response after COVID-19, drug-induced hepatotoxicity and direct cytotoxic effect of the virus. There are observations that SARSCoV-2 infection causes hepatitis B virus reactivation, but little has been described about the interaction between hepatitis C virus and SARS-CoV-2. The course of coronavirus infection is associated with marked expression of proinflammatory cytokines, participants in the multisystem inflammatory response, IL-1β, IL-6, IL-8, IL-18, MCP-1, TNFα, which contribute significantly to the observed early and late liver function impairment. The aim of the study was to evaluate the role of proinflammatory cytokines (VEGFA, IL-8, IL-6, MCP-1, TNFα, IL-18) as additional markers of hepatotoxicity after COVID-19. The study was performed between March and August 2022. Patients were divided into 2 groups: Group 1 – with increased aminotransferases against the background of treatment from COVID-19 and/or in the following 3-6 months after the disease without viral liver damage (n = 42), Group 2 – patients with co-infection (chronic viral hepatitis C (HCV) and COVID-19 (n = 26). The levels of cytokines – VEGF-A, IL-6, IL-8, MCP-1, IL-18, TNFα in blood serum were estimated by enzyme immunoassay method. Statistical analysis was performed using StatTech v. 3.1.4. The results of the study revealed a comparable increase in the level of transaminases and C-reactive protein in both groups, significantly different from the reference values. Direct correlations of moderate strength (linear Spearman correlation) were found between the following cytokines: TNFα-MCP-1 (R = 0.559; p = 0.001), TNFα-VEGFA (R = 0.400; p = 0.002), TNFα-IL-6 (R = 0.503; p = 0.001). We diagnosed a significant increase in serum VEGFA levels in group 1 patients (hepatotoxicity after COVID-19) (Me (Q0.25-Q0.75): 522 (250 to 1002), p = 0.001) and in group 2 patients (HCV + COVID-19) (Me 1196, Q0.25-Q0.75: (73 to 432). Similar trend with the level of IL-6, IL-8, exceeding the values of cytokines in healthy donors and significantly higher than in group 2 patients. Identified correlations between inflammatory cytokines prove unidirectional changes in the functioning of the regulatory network controlling immune virus-induced reactions.
Pleiotropic immunomodulating effects of peptide Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on various subsets of neutrophilic granulocytes and their phenotype in patients with COVID-19 in vitro
Authors: Gorodin V. N. , Matushkina V. A. , Chapurina V. N. , Menyailo A. I. , Kovaleva S. V. , Dydyshko E. I.
Published: June 2023

The key role of neutrophilic granulocytes (NG) in the pathogenesis of COVID-19 makes them new targets for therapeutic approaches and of influencing the course and outcome of the disease, restoring changes in the phenotype and functions of NG. Synthetic peptides or polypeptide complexes of action are the most promising in the treatment of COVID-19. Aim: to reveal the effects of the influence of the hexapeptide (HP) – Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on the phenotype of functionally significant NG subsets in moderate COVID-19.

The study examined patients 61 (57-71) years old (n = 45) in the acute period of COVID-19 – study group1 (SG1). In vitro, samples SG1 were incubated with HP (106 g/L, 60 min, 37 °C) – study group2 (SG2). The number of NG subsets was evaluated: CD16+IFNα/βR1+CD119+, CD16+IFNα/βR1+CD119- , CD16+IFNα/βR1+CD119+, CD64- CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and phenotype by membrane receptor expression density (MFI) (FC 500, Beckman Coulter, USA); NG phagocytic activity was tested before and after incubation with HP. The comparison group (GS) – of 22 volunteers examined in the pre-COVID period.

It was revealed that unidirectional effects of HP in vitro contributing to the restoration of the phenotype of subsets CD16+IFNα/βR1- CD119+, CD16+IFNα/βR1+CD119- to CG indicators. There was a decrease in MFI CD16 (p < 0.05) in both subsets; MFI CD119 (p < 0.05) in the CD16+IFNα/βR1- CD119+NG subset, MFI IFNa/βR1 in the CD16+IFNα/βR1+CD119- NG subset. The effects of HP on the phenotype of CD16+IFNα/βR1+CD119+NG subsets in 76% of cases were manifested by a decrease in MFI CD16 (p<0.05), an increase in MFI IFNα/βR1 and CD119 (p1, 2<0.05), and in 24% of cases a decrease in MFI IFNα/βR1 (p<0.05). HP in vitro remodeling of the phenotypes subsets CD64- CD16+CD32+CD11b+ and CD64+CD16+CD32+CD11b+ were established, providing the usefulness of effector functions from hyperactivated to normal. In the CD64- CD16+CD32+CD11b+ subset, there was a decrease in MFI CD16 and CD11b to the indicators CG (p1, 2 < 0.05). Recovery of the NG phenotype under the influence of HP led to the restoration of the phagocytic function of NG.

Positive effects of HP in vitro on the phenotypes of subsets actively and NGfunctions in COVID-19 open up prospects for the creation of new methods of immunotherapy to restore NG dysfunctions.
Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile
Authors: Lazareva N. M. , Kudryavtsev I. V. , Baranova O. P. , Isakov D. V. , Serebriakova M. K. , Bazhanov A. A. , Arsentieva N. A. , Liubimova N. E. , Ses’ T. P. , Ilkovich M. M. , Totolian A. A.
Published: June 2023

Immune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subsets and relevant signature cytokines. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): 18% with acute and 82% with chronic course. The control group — samples from healthy volunteers (n = 43). T cell subset composition was assessed by flow cytometry. Cytokine concentrations (pg/mL) were measured by multiplex analysis using xMAP technology (Luminex). The level of “classical” Th17 turned out to be significantly reduced in acute vs chronic sarcoidosis: 28.3% vs 33.3% (p = 0.046). The level of “double-positive” Th17 (DP Th17) was significantly increased in chronic and acute vs control group: 31.7% and 34.2% vs 26.2% (p < 0.001 in both cases), without differences patient inter-group; “non-classical” Th17.1 were shown to have significantly reduced level only in chronic vs healthy subjects: 27.9% and 35.9% (p < 0.001). Clinical and laboratory diagnostic characteristics for blood DP Th17 levels in CD45RA-negative Th effector memory cells in sarcoidosis: in acute sarcoidosis vs healthy subjects, they were characterized by sensitivity — 82%; specificity — 71%, whereas in chronic: 67% and 56%, respectively. In patients with sarcoidosis vs healthy subjects were found to have significantly increased level of IL-12 (p70) — 1.3 vs 0.56, p = 0.028; IL-17A — 1.5 vs 0.43, p < 0.001; IFNγ — 4.1 vs 1.1, p < 0.001; TNFα — 21.7 vs 6.7, p < 0.001. Thus, CCR6+ Th17 and DP Th17 subsets and relevant signature cytokines are important in diagnostics of sarcoidosis of varying clinical course: a direct correlation was shown between the level of angiotensin-converting enzyme activity and percentage of memory DP Th17; disease progression vs regression had significantly reduced absolute number of total CD45RA- memory and CM Th17; extrapulmonary manifestations had a significantly increased percentage of DP Th17 CD45RA- and EM DP Th17; in chronic sarcoidosis are significantly increased concentration of IL-17A, IFNγ, IL-12 and positively correlation between IFNγ and the activity of angiotensin-converting enzyme.
T regulatory lymphocytes and FoxP3 nuclear translocation in various adipose tissue depots in patients with coronary artery disease
Authors: Kologrivova I. V. , Dmitriukov A. A. , Kharitonova O. A. , Kravchenko E. S. , Naryzhnaya N. V. , Koshelskaya O. A. , Suslova T. E.
Published: June 2023

T regulatory lymphocytes (Treg) are present is adipose tissue. Their frequency, as well as the level of FoxP3 nuclear translocation, in epicardial and thymus adipose tissue remains unexplored. Properties of adiposeresident Tregs may be of high significance in patients with coronary artery disease as potential pathophysiological factor in the development of atherosclerosis. The aim of the study was to compare frequency of FoxP3+Tregs and FoxP3 nuclear translocation in epicardial, thymus, subcutaneous adipose tissue and peripheral blood in patients with coronary artery disease. A pilot study was conducted in 11 patients with coronary artery disease scheduled for the coronary artery bypass graft surgery after prior selective coronary angiography. Frequency of CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ lymphocytes and FoxP3 nuclear translocation were evaluated by imaging flow cytometry in peripheral blood and in stromal vascular fraction of epicardial, subcutaneous and thymus adipose tissue. Frequencies of CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ lymphocytes were higher in epicardial adipose tissue compared to blood (3 and 5 times higher, p = 0.020); CD4+CD25loFoxP3+ cells frequency in subcutaneous adipose tissue was 4 times higher than in blood (p = 0.028). The level of FoxP3 nuclear translocation was the highest in blood and decreased in epicardial, subcutaneous and thymus adipose tissue (p = 0.020 both for CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ lymphocytes). Frequency of CD4+CD25loFoxP3+ cells was directly related to age in thymus (rs = 0.818; p = 0.002), and inversely in epicardial adipose tissue (rs = -0.618; p = 0.043). Frequencies of CD4+CD25hiFoxP3+ and CD4+CD25loFoxP3+ with FoxP3 nuclear translocation in subcutaneous adipose tissue negatively correlated with age (rs = -0.827; p = 0.002 and rs = -0.648; p = 0.031, respectively). Frequency of CD4+CD25loFoxP3+ cells with FoxP3 nuclear translocation in thymus adipose tissue negatively correlated with waist-to-hip ratio (rs = -0.700; p = 0.016). The severity of atherosclerosis was related only to the frequency of CD4+CD25loFoxP3+ cells in subcutaneous adipose tissue (rs = -0.655; p = 0.029). Thus, epicardial and subcutaneous adipose tissue are enriched with Tregs, but factors that influence Treg accumulation and FoxP3 nuclear translocation in these fat depots may be different. The obtained results may further be used for personalized immunomodulatory therapy in patients with atherosclerosis.
Umbilical cord blood as a promising source of NK cells for immunotherapy
Authors: Velichinskii R. A. , Vavilova J. D. , Boyko A. A. , Shustova O. A. , Palamarchuk A. I. , Yusubalieva G. M. , Kucherova O. N. , Streltsova M. A. , Kovalenko E. I.
Published: June 2023

Currently, a large number of studies on genetic modification of cord blood NK cells (UCB-NK) are carried out at both clinical and preclinical levels. Immunotherapy based on UCB-NK cells has great potential for antitumor therapy. However, despite having known several advantages over peripheral blood NK cells (PB- NK), including a high concentration in cord blood and low virulence rate, UCB-NK cells are predominantly characterized in the scientific literature as immature and low-functioning NK cells. In this work, we studied the phenotypic characteristics of UCB-NK cells and the possibility of stimulatory compensation of the decreased functional activity of UCB-NK cells. Our studies revealed UCB-NK cells can be characterized as poorly differentiated and weakly activated cells with high level of inhibitory receptor NKG2A and low level of activating receptor NKG2C and HLA-DR, accordingly with the literature data. Two types of stimuli were chosen to stimulate freshly isolated UCB-NK cells: 1) 100 units of IL-2; 2) combinations of 100 units IL-2 and K-562 feeder cells expressing membrane-bound IL-21 (K562-mbIL21). It was shown the degranulation (LAMP-1) and proliferative activity was higher than for parallel cultured ex vivo PB-NK cells under the same conditions for UCB-NK cells stimulated for 7 days with IL-2 + K562-mbIL21. Moreover, stimulation in the way of IL-2 + K562-mbIL21 seemed to be a more perspective way to obtain a large number of proliferatively active UCB-NK cells compared to stimulation with IL-2 only. Since genetic modification of NK cells is a promising way to improve the antitumor properties of NK cells, retroviral transduction procedure was performed to study of the stimulated UCB-NK cells. UCB-NK cells stimulated with IL-2 + K562-mbIL21 were transduced on day 8 of cultivation. In this study, we used targeted overexpression of the adaptor molecule DAP12, which is involved in the signaling of activating NK cell receptors. PB-NK cells and UCB-NK cells were transduced under the equal experimental conditions in same volume of viral particles. As a result, the transduction efficiency was found to be more than 4-fold higher for UCB-NK cells compared to PB-NK cells. Thus, UCB-NK cells appear to be a promising tool for further research in cancer immunotherapy.
Regional Drought Analysis with Standardized Precipitation Evapotranspiration Index (SPEI): Gediz Basin, Turkey
Authors: ÖNEY Mustafa , ANLI Alper
Published: June 2023

In this study, regional drought analysis was performed with the Standard Precipitation Evapotranspiration Index (SPEI) and L moments techniques by using the monthly average temperature and monthly total rainfall amounts collected from five sites in the Gediz basin in Turkey. Using the monthly average temperatures, the potential evapotranspiration (PET) amounts obtained by the Thornthwaite method and the monthly total rainfall amounts are divided into 5 different reference periods as 1, 3, 6, 9 and 12 months. Expressing the difference between rainfall and potential evapotranspiration amounts, the water balance (Di) series shows that almost all of the 9 and 12 months periods suffers from water deficiency and the 3 months period is water excessive. After determining the distributions that provide the best adaptation to the water balance series, according to the SPEI values obtained, near-normal conditions prevailed in all sites, while moderate and severe arid and humid conditions sometimes occur, while extremely humid and arid conditions are rarely seen. In the regional drought analysis using L moment techniques with the SPEI values obtained, a region of 5 sites was accepted and the irregularity and heterogeneity measures showed that the basin was acceptable homogeneous. SPEI values are generally the best fit generalized extreme values (GEV) for 1 and 3 months periods, generalized normal (GNO) for 6 months period, generalized logistics (GLO) for 9 months period, Pearson type 3 (PE3) distributions for 12 months period. According to the regional SPEI values for reference periods, it has been found near-normal in 1.11, 1.25 and 2 years, moderately humid in 1.04 years, very humid conditions for 1.01 and 1.02 years, moderately dry in 4 and 5 years, severe arid in 10 years, and extremely dry conditions in 20 and longer periods.
RELAÇÃO ENTRE PRESSUPOSTOS TEÓRICOS, CURRÍCULO E ORGANIZAÇÃO DO ENSINO
Authors: LIZZI MARIA SANDREANA SALVADOR DA SILVA , SFORNI MARTA SUELI DE FARIA
Published: June 2023

RESUMO: Na elaboração de currículos escolares e projetos políticos pedagógicos (PPPs) é exigido que sejam evidenciados os pressupostos teóricos, os encaminhamentos metodológicos e os processos de avaliação. Todavia, nem sempre esses elementos são vistos de modo articulado, por isso, esses documentos não orientam o trabalho pedagógico. A partir dessa problemática, este artigo, com o objetivo de evidenciar a relação entre o currículo prescrito e as ações de ensino, apresenta parte de uma pesquisa, de natureza qualitativa, cujos dados de campo foram coletados em um grupo de estudos do qual participaram professores envolvidos na elaboração de uma proposta curricular fundamentada no materialismo histórico-dialético, na teoria histórico-cultural e na pedagogia histórico-crítica. Os resultados apontam que a participação dos professores no processo de elaboração de currículos e de PPPs provoca neles reflexões acerca da articulação desses documentos com a prática pedagógica e gera a necessidade de compreender ações de ensino que podem ser derivadas dos fundamentos anunciados no currículo.
APOSTAS FORMATIVAS DE PORTFÓLIOS COLETIVOS EM DIÁLOGO COM A PESQUISA CIENTÍFICA
Authors: ANTIQUEIRA LILIANE SILVA DE , PEREIRA ELAINE CORRÊA , GALIAZZI MARIA DO CARMO
Published: June 2023

RESUMO: Apresenta-se o mapeamento de pesquisas sobre o uso de portfólios na formação de professores, com o objetivo de identificar proposições oriundas das pesquisas e relacioná-las com as apostas formativas assumidas em todos os editais aprovados pela Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) no Programa Institucional de Bolsas de Iniciação a Docência (PIBID) de uma Instituição de Ensino Superior (IES) para o uso de portfólios. Apresenta-se brevemente o PIBID, e descreve-se o mapeamento de artigos científicos em suas três etapas: identificação, classificação e análise. Faz-se a classificação dos artigos em regiões geográficas, percebendo-se que a temática está espalhada em todas as regiões brasileiras e que o mesmo se observa em relação às produções internacionais. A etapa de análise consistiu em uma categorização à luz da Análise Textual Discursiva (ATD). As categorias resultantes abordaram pesquisas sobre: o portfólio em si; o portfólio para avaliação do professor; o portfólio como reflexão do estudante; o portfólio como registro da rede de formação; o portfólio como artefato institucional para certificação; o discurso dos participantes sobre os portfólios; e o discurso bibliográfico sobre os portfólios. Concluiu-se que existe ressonância entre as apostas formativas assumidas para o uso de portfólios no PIBID de uma IES e as categorias de análise, com exceção da aposta na potência epistêmica da escrita. Algumas categorias resultantes do mapeamento também não apareceram como aposta formativa: o portfólio para avaliação do professor, o portfólio como artefato institucional para certificação e o olhar sobre o portfólio em si.
EDUCATION PROPOSALS WITH THE USE OF COLLECTIVE PORTFOLIOS IN DIALOGUE WITH SCIENTIFIC RESEARCH
Authors: ANTIQUEIRA LILIANE SILVA DE , PEREIRA ELAINE CORRÊA , GALIAZZI MARIA DO CARMO
Published: June 2023

ABSTRACT: An overview of research on the use of portfolios in teacher education is presented, in order to identify propositions arising from the research and relate them to education proposals assumed in all of the public notices approved by Coordination for Improvement of Higher Education Personnel (CAPES) in Institutional Teacher Training Scholarship (PIBID) of a Higher Education Institution (IES) for the use of portfolios. PIBID is briefly presented, and the mapping of scientific articles is described in its three stages: identification, classification and analysis. The classification of articles according to geographic regions has enabled us to realize that the theme is spread across all Brazilian regions and that the same is observed in relation to international productions. The analysis stage consisted of a categorization in the light of Discursive Textual Analysis. The resulting categories addressed research on: the portfolio itself; the portfolio for teacher evaluation; the portfolio as a student's reflection; the portfolio as a record of the training network; the portfolio as an institutional artifact for certification; the discourse of the participants about the portfolios; and the bibliographic discourse on portfolios. It has been concluded that there is resonance between the education proposals assumed for the use of portfolios in PIBID of an IES and the categories of analysis, with the exception of the proposal on the epistemic potency of writing. Some categories resulting from the mapping did not appear as education proposals: the portfolio for teacher evaluation, the portfolio as an institutional artifact for certification, and the portfolio by itself.
CURRÍCULOS E SIGNOS ARTÍSTICOS EM TORNO DE UMA EDUCAÇÃO CONTRACULTURAL
Authors: CARVALHO JANETE MAGALHÃES , SILVA SANDRA KRETLI DA
Published: June 2023

RESUMO: O artigo argumenta sobre o modo como os currículos que utilizam a arte com seus signos sensíveis podem possibilitar um movimento do pensamento em torno de uma educação contracultural que afirma a vida em contraponto aos processos de sujeição capitalistas. Dialoga, com intercessores teóricos pós-fundamentalistas, acerca das conceituações de culturas, de currículos, de docências, das imagens de signos artísticos em sua relação com a formação de um povo por vir. Metodologicamente trata-se de uma pesquisa-formação realizada com professoras de uma rede municipal de ensino, de modo virtual via Google Meet, no ano de 2021. Objetiva, portanto, pensar a força dos signos artísticos nas invenções e composições culturais e curriculares. Exemplifica, nos resultados, alguns desestabilizadores que professoras, nos encontros com os signos das artes, escavam, que abrem fissuras no pensamento dogmático - pensamento como representação - abrindo frestas para a passagem de um pensamento nômade que escapa, que experimenta e cria aberturas para passagem dos fluxos de forças imagéticas e conversacionais de modo a expandir processos de diferenciação e assim inventar novas imagens para as escolas, para as culturas e para os currículos com a força da diferença.
VELOCIDADE CRÍTICA, VO2MAX E LIMITES DE O DOMÍNIO DE INTENSIDADE DE EXERCÍCIO SEVERO
Authors: Hill David Wilfred , Glass Linda Weaver , Vingren Jakob Langberg
Published: June 2023

RESUMO Introdução: O domínio de intensidade de exercício severo pode ser definido como a faixa de taxas de trabalho ou velocidades sobre as quais o VO2max pode ser obtido. Objetivos: Nosso propósito foi determinar se a velocidade crítica (execução analógica da potência crítica) identifica o limite inferior do domínio severo e identificar o limite superior do domínio. Métodos: Vinte e cinco indivíduos realizaram cinco testes de corrida até a exaustão, cada um com duração > 2,5 min e < 16 min. A relação velocidade de dois parâmetros contra tempo até a exaustão gerou valores para a velocidade crítica e a relação velocidade de três parâmetros contra tempo para alcançar o VO2max valores gerados para a velocidade limite acima da qual o VO2max pode ser obtido. As relações foram resolvidas para calcular o tempo mínimo necessário para eliciar o VO2max. Resultados: A velocidade crítica (3,00 ± 0,38 m·s−1) e a velocidade limite acima da qual o VO2max pode ser eliciado (2,99 ± 0,37 m·s−1) foram correlacionadas (r = 0,83, p < 0,01) e não diferiram (p = 0,70), confirmando a velocidade crítica como o limite inferior do domínio grave. O tempo mínimo necessário para eliciar o VO2max (103 ± 7 s) e a maior velocidade associada na qual o VO2max pode ser eliciado (4,98 ± 0,52 m·s−1) identificou o limite superior do domínio severo para esses participantes. Conclusão: O conceito de potência crítica, que não requer medidas metabólicas, pode ser usado para identificar a velocidade mais baixa em que o VO2max pode ser eliciado. Com a adição de medidas metabólicas, a modelagem matemática também pode identificar a velocidade mais alta e a duração mais curta do exercício em que o VO2max pode ser obtido. Nível de Evidência I; Estudo de coorte com alto padrão de referência.