Imbalance of NK cell subpopulations and polymorphisms of proinflammatory cytokine genes in the pathogenesis of atherosclerosis

Understanding the pathogenetic mechanism of development and identifying trigger markers of the disease will significantly increase the efficiency of pre-nosological diagnosis and medical follow-up of patients. In this case, one should take into account the role of mutations in cytokine genes, which affect their biochemical activity and production level. The objective of the study was to investigate the role of mediators of acute and chronic inflammation (IL-17A, IL-1â, TNFá and IL-4), the ratio of natural killer cell subpopulations (CD56hiCD16-/CD56loCD16+) in pathogenesis of coronary atherosclerosis resulting into coronary heart disease.To analyze the results, an integrated approach was used, including molecular genetic methods such as polymerase chain reaction, typing of single-nucleotide substitutions in cytokine genes, isolation and cultivation of peripheral blood mononuclear cells, assessment of spontaneous and in vitro-induced production of immune system mediators, enzyme-linked immunosorbent assay, cytotoxic test, flow cytometry with monoclonal antibodies (Beckman Coulter, USA) to CD16, CD56 NK markers.The study included 130 residents of the North Caucasus, including the patients (n = 62) treated at the Cardiology Department of the Adyghe Republican Clinical Hospital (ARCB) with a verified diagnosis of ischemic heart disease (IHD), and a control group (n = 68), represented by unrelated healthy donors.Overexpression of cytokines in IHD patients was associated with distinct single nucleotide substitutions in certain genes. Studying a group of residents from the Republic of Adygeya, the authors experimentally established that harboring the 511C allele of the IL-1â gene (p < 0.0004; OR = 4.67), A197A of the IL-17A gene genotype (p < 0.04; OR = 3.88), G308 SNP of TNFá gene (p < 0.01; OR = 3.41), and 589T variant of IL-4 gene (p < 0.04; OR = 2.45) are associated with hyperproduction of the first-wave inflammatory mediators that increase the risk of developing ischemic heart disease. In atherosclerosis and associated cardiovascular diseases, we have noted a significant decrease in spontaneous and induced activity of natural killer cells involved in the utilization of “foamy cells”. The NK activity of peripheral blood mononuclear cell in patients with coronary heart disease is significantly reduced. In the IHD patients, an imbalance of phenotypically and functionally different CD56hiCD16-/CD56loCD16+ NK subpopulations with a predominance of CD56hiCD16- phenotype were revealed. Conclusions: Immuno-inflammatory mechanisms of evolving coronary atherosclerosis are associated with single-nucleotide substitutions, i.e., polymorphisms in the promoter regions of the IL-17A (G197A), IL-1 â (T511C), and TNFá (G308A), the known mediators of acute and chronic inflammation.Genetically determined overexpression of IL-17A, IL-1â, and TNFá, confirmed in experiments on evaluation of spontaneous and stimulated cytokine production in patients with CHD, together with reduced NK activity of РВМС, due to predominance of CD56hiCD16-, a subpopulation with high cytokine production, manifested by an increased pro-inflammatory component that triggers and provides long-term support to pathophysiological processes of atherosclerosis

Cognitive status in older patients with limited mobility as a predictor of negative outcome

Background. Cognitive impairment (CI) is one of the important disability factors in the elderly. The role of CI in prognosis of the frailest patients with limited mobility is uncertain.The aim. To determine the influence of the initial cognitive status in the group of patronage patients aged 60 years and older on the risk of mortality within one year.Materials and methods. Study group consisted of 450 patients from patronage group with one-year period of observation (from July 2019 till July 2020). Initial physical, functional, neuropsychiatriac and social statuses were evaluated by comprehensive geriatric assessment. Cognitive impairment was screened by Mini-Mental State Examination (MMSE), with dividing patients into dementia group (MMSE ≤ 24) and no-dementia group (MMSE > 24). The mortality rate after one year was assessed.Results. Of the 450 patients included in the study, dementia was present in 44.2 %. Patients with dementia were more prone to greater severity of chronic pain, sleep disturbances, depression, malnutrition and anemia. After one year of observation 34 out of 196 patients (17.3 %) in the group of patients with dementia and 18 out of 248 patients (7.3 %; p = 0.002) in the no-dementia group died. According to multivariate analysis, independent risk factors for death in patients with dementia were anemia, hearing impairment and a history of bone fractures.Conclusion. Thus, the assessment of the cognitive status of frail patients with limited mobility is important for the purpose of identifying the most vulnerable individuals with a high risk of adverse outcomes

High-Temperature Interactions of Silicon-Aluminum Oxynitrides (Sialons) with Sodium Fluoride

The high-temperature interactions of β-SiAlONs with sodium fluoride NaF at 1650 °C under a nitrogen atmosphere are described in this paper. It was found that in case of Si5AlON7 the formation of phases enriched with aluminum occurred, including Si4Al2O2N6 at an NaF loading of 0.5 wt.% and Si4Al2O2N6 and Si3.1Al2.9O2.9N5.1 at an NaF loading of 2.0 wt.%, although Si5AlON7 still was a major phase. For Si4Al2O2N6, a kind of disproportionation was observed, and Si5AlON7 formed together with Si3Al3O3N5 and Si3.1Al2.9O2.9N5.1. Moreover, the initial phase Si4Al2O2N6 was not identified at all, while Si5AlON7 was found to be a major phase at an NaF loading of 0.5 wt.% and Si3.1Al2.9O2.9N5.1 prevailed at an NaF loading of 2.0 wt.%. All the samples showed a high degree of densification when studied with scanning electronic microscopy

Investigation of the Effect of Supersonic Flow of Dissociated Nitrogen on ZrB₂–HfB₂–SiC Ceramics Doped with 10 vol.% Carbon Nanotubes

The method of fabricating dense ultra-high temperature ceramic materials ZrB2–HfB2–SiC–CCNT was developed using a combination of sol-gel synthesis and reaction hot pressing approaches at 1800 °C. It was found that the introduction of multilayer nanotubes (10 vol.%) led to an increase in the consolidation efficiency of ceramics (at temperatures > 1600 °C). The obtained ZrB2–HfB2–SiC and ZrB2–HfB2–SiC–CCNT materials were characterized by a complex of physical and chemical analysis methods. A study of the effects on the modified sample ZrB2–HfB2–SiC–CCNT composition speed flow of partially dissociated nitrogen, using a high-frequency plasmatron, showed that, despite the relatively low temperature established on the surface (≤1585 °C), there was a significant change in the chemical composition and surface microstructure: in the near-surface layer, zirconium–hafnium carbonitride, amorphous boron nitride, and carbon were present. The latter caused changes in crucial characteristics such as the emission coefficient and surface catalyticity

Short-Term Oxidation of HfB₂-SiC Based UHTC in Supersonic Flow of Carbon Dioxide Plasma

The short-term (5 min) exposure to the supersonic flow of carbon dioxide plasma on ultrahigh-temperature ceramics of HfB2-30vol.%SiC composition has been studied. It was shown that, when established on the surface at a temperature of 1615–1655 °C, the beginning of the formation of an oxidized layer takes place. Raman spectroscopy and scanning electron microscopy studies showed that the formation of a porous SiC-depleted region is not possible under the HfO2-SiO2 surface oxide layer. Numerical modeling based on the Navier–Stokes equations and experimental probe measurements of the test conditions were performed. The desirability of continuing systematic studies on the behavior of ultrahigh-temperature ZrB2/HfB2-SiC ceramics, including those doped with various components under the influence of high-enthalpy gas flows, was noted