Репозиторий Университета

© 2021, The Author(s). Background: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer’s and Parkinson’s disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. Methods: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. Results: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. Conclusion: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

© 2021, The Author(s). Background: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer’s and Parkinson’s disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. Methods: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. Results: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. Conclusion: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Objectives. To study the relationship between the immune system and depression, as well as its endophenotypes (neuroticism and trait anxiety), in patients with ischemic heart disease (IHD). Materials and methods. Studies were performed in a group of men with IHD and depression (78 patients) and without depression (91 patients), as well as in healthy male volunteers (127 subjects). Polymorphisms of the interleukin-4 (IL-4 –589C/T), interleukin-6 (IL-6 –174G/C), tumor necrosis factor α (TNF-α –308G/A), and C-reactive protein (CRP –717A/G) genes were studied. Results. An association between the IL-6 –174G/C polymorphism with depression comorbid with IHD was found (p = 0.01, OR = 2.3, 95% CI = 1.2–4.3), which was apparent as an increase in the frequency of the highly expressed G allele in the group of patients with depression. The IL-4 –589C/T polymorphism was associated with IHD: the frequency of the CC IL-4 –589C/T genotype was greater in this group of patients than in the control group regardless of the presence of depression (p = 0.007, OR = 2.1, 95% CI = 1.2–3.4). The TNF-α –308G/A and CRP –717A/G polymorphisms were not associated with depression in IHD. There were no signifi cant differences in the expression of neuroticism or trait anxiety in carriers of different genotypes at the IL-4 –589C/T, IL-6 –174G/C, TNF-α –308G/A, or CRP –717A/G loci. Conclusions. The association between the IL-6 –174G/C polymorphism with depression comorbid with IHD is consistent with published data on the role of IL-6 in the depression of depression in cardiology patients.

© 2018 Chernokhaeva, Rogova, Kozlovskaya, Romanova, Osolodkin, Vorovitch and Karganova. Tick-borne encephalitis (TBE), caused by the TBE virus (TBEV), is a serious public health threat in northern Eurasia. Three subtypes of TBEV are distinguished. Inactivated vaccines are available for TBE prophylaxis, and their efficacy to prevent the disease has been demonstrated by years of implication. Nevertheless, rare TBE cases among the vaccinated have been registered. The present study aimed to evaluate the protective efficacy of 4 TBEV vaccines against naturally circulating TBEV variants. For the first time, the protection was evaluated against an extended number of phylogenetically distinct TBEV strains isolated in different years in different territories. The protective effect did not strongly depend on the infectious dose of the challenge virus or the scheme of vaccination. All vaccines induced neutralizing antibodies in protective titers against the TBEV strains used, although the vaccines varied in the spectra of induced antibodies and protective efficacy. The protective efficacy of the vaccines depended on the individual properties of the vaccine strain and the challenge virus, rather than on the subtypes. The neutralization efficiency appeared to be dependent not only on the presence of antibodies to particular epitopes and the amino acid composition of the virion surface but also on the intrinsic properties of the challenge virus E protein structure.

© 2018 Informa UK Limited, trading as Taylor  &  Francis Group. Over the last decade, a dual character of cell response to oxidative stress, eustress versus distress, has become increasingly recognized. A growing body of evidence indicates that under physiological conditions, low concentrations of reactive oxygen and nitrogen species (RONS) maintained by the activity of endogenous antioxidant system (AOS) allow reversible oxidative/nitrosative modifications of key redox-sensitive residues in regulatory proteins. The reversibility of redox modifications such as Cys S-sulphenylation/S-glutathionylation/S-nitrosylation/S-persulphidation and disulphide bond formation, or Tyr nitration, which occur through electrophilic attack of RONS to nucleophilic groups in amino acid residues provides redox switches in the activities of signalling proteins. Key requirement for the involvement of the redox modifications in RONS signalling including ROS-MAPK, ROS-PI3K/Akt, and RNS-TNF-α/NF-kB signalling is their specificity provided by a residue microenvironment and reaction kinetics. Glutathione, glutathione peroxidases, peroxiredoxins, thioredoxin, glutathione reductases, and glutaredoxins modulate RONS level and cell signalling, while some of the modulators (glutathione, glutathione peroxidases and peroxiredoxins) are themselves targets for redox modifications. Additionally, gene expression, activities of transcription factors, and epigenetic pathways are also under redox regulation. The present review focuses on RONS sources (NADPH-oxidases, mitochondrial electron-transportation chain (ETC), nitric oxide synthase (NOS), etc.), and their cross-talks, which influence reversible redox modifications of proteins as physiological phenomenon attained by living cells during the evolution to control cell signalling in the oxygen-enriched environment. We discussed recent advances in investigation of mechanisms of protein redox modifications and adaptive redox switches such as MAPK/PI3K/PTEN, Nrf2/Keap1, and NF-κB/IκB, powerful regulators of numerous physiological processes, also implicated in various diseases.

© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. Background: Elevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, have been consistently reported in chronic spontaneous urticaria (CSU). Here, we retrospectively analyzed data from 1253 CSU patients from 2 centers to answer the following questions: (i) What is the prevalence of elevated levels of CRP in CSU? (ii) Why do CSU patients show elevated levels of CRP? (iii) Are elevated CRP levels relevant?. Methods: Serum levels of CRP were measured by the nephelometric method. We collected information regarding various laboratory tests including ESR, CBC with differential, D-dimer, fibrinogen, C3, C4, IL-6, etc. For most patients, we also collected data on age, gender, duration of CSU, presence of angioedema, activity (UAS at the time of blood sampling and for 7 days), quality of life (CU-Q2oL and/or DLQI), comorbidities and possible causes of CSU, and autologous serum skin test (ASST) response. The efficacy of second-generation antihistamines was evaluated on the day of blood collecting. Results: One-third of CSU patients had elevated levels of CRP. Higher levels of CRP were associated with ASST positivity (P =.009) and arterial hypertension (P =.005), but not with other possible causes or comorbidities of CSU. C-reactive protein correlated with urticaria activity (P <.001), quality of life impairment (P =.026), and inflammatory and coagulation markers (P <.001). C-reactive protein levels were significantly higher in nonresponders to antihistamines as compared to responders (P <.001). Conclusion: Elevated levels of CRP are common and relevant in CSU patients. The assessment of CRP levels may help to optimize the management of patients with CSU.

© 2017 Elsevier Inc. A wide range of methods are known to increase the prokaryotic intracellular recombinant proteins solubility, for instance, growth at low temperature, supplementation of culture media with “chemical chaperones” (proline, glycine-betaine, and trehalose), co-expression with chaperones or highly soluble fusion partners. As an alternative, we have introduced the polyglutamate tag, which, as it has been shown, increased the protein solubility and facilitated folding. In this study we evaluated the minimal quantity of high density negatively charged EEEEVE amino acid repeats (pGlu) necessary to switch the recombinant receptor-binding domain of human alpha-fetoprotein (rbdAFP) expression almost entirely from the inclusion bodies to the soluble cytoplasmic fraction in E. coli. For this purpose, genetic constructs based on pET vectors coding rbdAFP and containing from 1 to 4 additional EEEEVE repeats at the C-terminus have been prepared. It was found that 3 pGlu repeats is the minimal number, that leads to a complete shift of the expression to the soluble cytoplasmic fraction in E. coli SHuffle Express T7 while 4 repeats were required for that in E. coli BL21(DE3). The rbdAFP contained 4 pGlu repeats was purified making use of ion-exchange chromatography and characterized by circular dichroism and ability to bind and accumulate in AFP receptor positive cancer cells in order to check for the structural and specific activity alterations related to the additional polyanionic sequence introduction.

© 2018 Stolichnaya Izdatelskaya Kompaniya. All rights reserved. Obesity is one of the leading and the most serious risk factors of cardiovascular diseases. Overweight provokes many metabolic and hemodynamic disorders. About 30% of inhabitants of the planet have overweight and prevalence of obesity increases by 10% every 10 years according to the WHO data. The probability of arterial hypertension in obese patients is 50% higher than in people with normal body mass. Framingham study showed that obesity is an independent, significant risk factor of ischemic heart disease, myocardial infarction, cerebral stroke and diabetes mellitus. The most dangerous is the central obesity with the preferential fat deposition in the abdomen. Combination of visceral obesity, violation of carbohydrate and lipid metabolism, arterial hypertension, and close pathogenic relationship between these factors underlie the isolated symptom complex known as metabolic syndrome. J. Vague was the first to describe relationship between abdominal obesity with cardiovascular disease and mortality in 1947. In our country G.F. Lang noticed common combination of arterial hypertension with obesity, lipid and carbohydrate metabolism disorders. Thus, metabolic syndrome significantly increases risk and severity of cardiovascular disease. Within last decades criteria of metabolic syndrome stays constant. The factors of insulin resistance and endothelial dysfunction as stages of the pathogenesis of the metabolic syndrome have been studied in detail. The mechanisms of insulin resistance and endothelial dysfunction are discussed in detail in this article as well as inflammatory markers and the significance of highly sensitive C-reactive protein.

© 2018 Ima-Press Publishing House. All rights reserved. Cognitive impairment (CI) is a basis for the clinical presentation of chronic cerebral ischemia (CCI). However, the role of the mechanisms of inflammation and angiogenesis in the origin of CI is unclear, as is its relationship to the number and localization of foci during a neuroimaging examination. Objective: to investigate the relationship between the presence of CI, focal brain tissue changes, and the plasma and serum levels of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) in patients with CCI. Patients and methods. Examinations were made in 59 patients with CCI and in 20 apparently healthy individuals. The investigators evaluated the cognitive status using the Mini-Mental State Examination (MMSE) and the clock drawing test), performed brain magnetic resonance imaging (MRI), duplex scanning of cerebral vessels, and determined laboratory indicators: the serum levels of MCP-1 and C-reactive protein, and the serum and plasma concentrations of VEGF. Results. The patients with CI were found to have higher values of inflammatory markers, lower serum and plasma concentrations of angiogenic factors, and a greater number of focal changes on MRI than those without CI (5.06±0.23 and 2.36±0.3 scores, respectively; p(0.05). Imbalance of angiogenic and antiangiogenic factors can cause disease progression and moderate vascular CI in patients with CCI.

© 2018 Bentham Science Publishers. Background: It was previously shown that inactivation of gamma-synuclein which is a small soluble neuronal protein affects psycho-emotional status and cognitive abilities in knock-out mice. Objective: Determine the role of gamma-synuclein inactivation on memory performance in aging animals. Method: We used the passive avoidance test and acute amphetamine administration in aging gammasynuclein knock-out mice. Results: As a result, we found moderate aging-unlinked deficit of dopaminergic neurotransmitter system of gamma-synuclein knock-out mice. At the same time, the evidence of progressive synaptic vesicle trafficking machinery impairment was obtained. Conclusion: Therefore most likely these dysfunctions are associated with a reduction in the highefficient learning performance in tests that require intact working memory.