Transformations of the Socio-Economic Space of Regions: International Experience and Main Trends

Today, management decisions in the field of regional development require the development of new concepts and theories that can explain the nature of the current economic situation. Governments, the scientific community, and even activists are busy with the development of regions and the transformation of their space. If we consider the scientific approach, then we should pay attention to the neoclassical models of territorial development. They have been the basis of economic growth for more than 50 years. Such models assume that not only for states, but also for separate regions, external demand and global competitiveness act as the main driving force of development. The high volatility of the space makes difficulties for countries and regions, which have to take on greater responsibility due to the decrease in the effectiveness of universal solutions to socio-economic problems. The question remains open in which direction to pursue strategic initiatives: to look back at past successful approaches or to form an agenda based on global trends. Both options carry significant risks of social upheaval and a decline in the quality of life of the population, which is unacceptable. This means that the price of taking decisions will only grow. In these conditions, it is necessary to understand the full range of expert assessments proposed to address issues related to the transformation of the socio-economic space of the regions. The purpose of this study is to review the international and Russian experience of regional management of socio-economic space and identify key directions of development

Methodological base of urban agglomerations and their suburban areas

The article forms methodological approaches to the study of urban agglomerations and their suburban areas. Basis and regularities of the social and economic development of urban agglomerations and suburban zones are determined. Data on definition of the territorial structure of urban agglomerations and their suburban areas is systematized. The basic regularities and laws of environmental complex formation in the region are highlighted. Cluster analysis has been used in order to establish a territorial structure of Krasnoyarskiy region. The main directions of the complex social and economic development of urban agglomerations and suburban areas are determined. The main problems of administrative allocation in urban agglomerations are highlighted

Action of extracellular divalent cations on native α-amino-3-hydroxy- 5-methylisoxazole-4-propionate (AMPA) receptors

The effects of divalent cations on Ca2+-impermeable containing (GluR2 subunit) MPA receptors of hippocampal pyramidal neurones isolated from rat brain was studied using patch-clamping. Ca2+, Mg2+, Mn2+, Co2+, Ni2+ and Zn2+ inhibited currents induced by kainate and glutamate. Inhibition was fast, reversible and voltage independent. The rank order of activities was Ni2+ > Zn2+ > Co2+ > Ca2+ > Mn2+ > Mg2+. Cyclothiazide (0.1 mM) significantly reduced inhibition by divalent cations and 6, 7 dinitroquinoxaline-2.3-dione (DNQX). However, high concentrations of Ni2+ and DNQX inhibited AMPA receptors even in the presence of cyclothiazide. The inhibitory effect of divalent cations as well as DNQX was counteracted by an increase in agonist concentration. In the presence of divalent cations the EC50 values of kainate and glutamate were increased, but the maximal response was not changed. An increase in agonist concentration induced a parallel shift in the concentration-inhibition curve for a divalent cation. These data suggest a competitive-like type of inhibition. However, an increase in agonist concentration reduced the inhibitory action of Ni2+ less than that of DNQX. This gave evidence against direct competition between divalent cations and AMPA receptor agonists. A 'complex-competition' hypothesis was proposed to explain the inhibitory action of divalent cations; it is suggested that divalent cations form ion-agonist complexes, which compete with free agonist for agonist-binding sites on AMPA receptors. © 2005 The Authors Journal Compilation © 2005 International Society for Neurochemistry

Synthesis and antifungal activity of monoterpenoids of the carane series

The antifUngal activity of terpenoids of the carane series was studied; an interaction was found between the structures of these compounds and their antifungal properties. The actions of several terpenoids on the adhesive activity and enzyme systems of the fungus Candida albicans were studied. © 2012 Springer Science+Business Media, Inc

Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression

Neurochemical mechanisms of initiation and expression of epileptic seizures are poorly explored, and there are no published data that could demonstrate the functional state of the neuromediator systems at the initial state of seizure in the animals genetically prone to seizure. In the current work, we studied the role of extracellular signal-regulated kinase (ERK1/2) in the regulation of the nigrostriatal glutamate, GABA and dopamine neurons of Krushinsky – Molodkina rats at clonus-tonus and ataxia stages of audiogenic seizure. We demonstrated upregulation of ERK1/2 activity upon audio stimulation which was accompanied by increased activation of Synapsin I in the striatum and substantia nigra in comparison to intact Krushinsky – Molodkina rats. The observed exocytosis activation led to secretion of glutamate in the striatum and, as a result, to stimulation of seizures. However, at clonus-tonus stage in the striatum we revealed the changes that could participate in further inhibition of seizure activity, such as increased phosphorylation of tyrosine hydroxylase upon increased ERK1/2 activity followed by activation of dopamine release in the pars compacta of the substantia nigra. At the same time, enhanced D2 and increased D1 dopamine receptor contents were observed. These data revealed attenuation of direct (pro-seizure) and indirect (anti-seizure) pathways of the regulation of the substantia nigra GABA neurons. We demonstrated activation of GABA in the substantia nigra pars reticulate, which probably results in the inhibition of glutamate neurons of the thalamus and could be one of the mechanisms inhibiting seizure activity during ataxia

The impact of Opisthorchis felineus infection and praziquantel treatment on the intestinal microbiota in children

peer reviewedThe presence of some species of helminths is associated with changes in host microbiota composition and diversity, which varies widely depending on the infecting helminth species and other factors. We conducted a prospective case-control study to evaluate the gut microbiota in children with Opisthorchis felineus infection (n=50) before and after anthelmintic treatment and in uninfected children (n=49) in the endemic region. A total of 99 children and adolescents aged between 7 and 18 years were enrolled to the study. Helminth infection was assessed before and at 3 months after treatment with praziquantel. A complex examination for each participant was performed in the study, including an assessment of the clinical symptoms and an intestinal microbiota survey by 16S rRNA gene sequencing of stool samples. There was no change in alpha diversity between O. felineus-infected and control groups. We found significant changes in the abundances of bacterial taxa at different taxonomic levels between the infected and uninfected individuals. Enterobacteriaceae family was more abundant in infected participants compared to uninfected children. On the genus level, O. felineus-infected participants’ microbiota showed higher levels of Lachnospira, Escherichia-Shigella, Bacteroides, Eubacterium eligens group, Ruminiclostridium 6, Barnesiella, Oscillibacter, Faecalitalea and Anaerosporobacter and reduction of Blautia, Lachnospiraceae FCS020 and Eubacterium hallii group in comparison with the uninfected individuals. Following praziquantel therapy, there were significant differences in abundances of some microorganisms, including an increase of Faecalibacterium and decrease of Megasphaera, Roseburia. Enterobacteriaceae and Escherichia abundances were decreased up to the control group values. Our results highlight the importance of the host-parasite-microbiota interactions for the community health in the endemic regions. © 202

Cytokine profile and expression of FYN, ZAP-70 and LAT during concanavalin a stimulation in patients with resistant bronchial asthma

Background: Bronchial asthma (BA) is one of the most spreading chronic lung pathology in the world. The disease is characterized by high heterogeneity of clinical phenotypes including resistant forms which provoke significant clinical problem. Immune shift from Th2 to alternative immunological response is considered to be a mechanism of drug-resistance in BA treatment but this issue is not considerably studied yet. Aims: Detection of distinctive patterns in cytokine secretion and genetic expression (ZAP-70, FYN and LAT) of naïve and concanavalin A stimulated lymphocytes in patients with resistant BA. Materials and methods: The study enrolled ten patients in each group: subjects with treatment resistant BA, severe BA, and controls (30 in total). During the experiment, all patients with BA received treatment according to the condition. For each participant lymphocytes isolation from venous blood was performed. Cells were cultured with concanavalin A and without stimulation. Concentrations of cytokines IL-2, IL-12, TNF-α, IL-4, IL-5, and IL-6 in supernatants were measured with ELISA. Reverse transcription polymerase chain reaction was used to detect the mRNA expression of LAT, ZAP-70, and FYN genes. Results: Significant disease contribution to the lymphocyte secretion profile was established without concanavalin A stimulation: increased levels of IL-2 and IL-4 was observed in lymphocytes of patients with resistant BA if compared to the results of gorup with severe BA. Patients with resistant BA were characterized by weak cytokine response to the stimulation: only TNF-α and IL-5 levels were significantly increased whereas in group with severe BA all cytokines concentrations increased except IL-12, in controls - except IL-12 and IL-2. Significant FYN upregulation was identified in resistant BA group if compared with other groups, and in severe BA patients if compared with controls. The concanavalin A-stimulated cells showed increased expression of ZAP-70 in cells of patients with resistant BA compared to control group. Conclusions: Lymphocytes from patients with resistant BA are characterized by lack of cytokine response to concanavalin A stimulation, alteration of cytokine secretion, and genetic expression profile similar to cells with low sensitivity to apoptosis. The FYN gene is a perspective target for finding approaches to overcome resistance to steroid drugs in bronchial asthma. © 2018 Izdatel'stvo Meditsina. All rights reserved

Изменение функционального профиля моноцитов крови при раке молочной железы

The purpose of the study was to identify functional features of circulation monocytes in patients with nonmetastatic breast cancer.Material and Methods. The study cohort consisted of 10 breast cancer patients treated at Tomsk Cancer Research Institute. 7 healthy female volunteers were enrolled as a control group. CD14+16-, CD14+16+ and CD14-16+ monocytes subsets were obtained from blood by sorting. Whole transcriptome profling was provided in monocytes from patients and healthy females. Macrophages were differentiated from the obtained monocytes under in vitro conditions. The ability of conditioned media obtained from macrophages to infuence apoptosis and proliferation of MDA-MB 231 cell line was evaluated.Results. Transcriptomic profling revealed signifcant changes in monocytes of breast cancer patients. CD14+16- subset showed higher expression of transporters ABCA1 and ABCG1; chemokines CCR1, CRRL2, CXCR4; maturation and differentiation factors Mafb and Jun; endocytosis mediating factors CD163 and Siglec1; proteases and tetrasponins ADAM9, CD151, CD82, and growth factor HBEGF in patient group. Macrophages derived from monocytes of breast cancer patients produced factors that supported proliferation of the MDA-MB 231 cell line, which was not observed for monocytes from healthy volunteers.Conclusion. Thus, breast carcinoma has a systemic effect on peripheral blood monocytes, programming them to differentiate into macrophages with tumor supporting capacity. Цель исследования ‒ оценить особенности функционального профиля моноцитов периферической крови у больных неметастатической формой рака молочной железы.Материал и методы. В исследование вошли 10 больных раком молочной железы II–III стадии (T1–3N0–2M0). В качестве контроля была обследована группа из 7 здоровых женщин. Моноциты были получены из периферической крови путем сортировки популяций с фенотипом CD14+16-, CD14+16+ и CD14-16+. Проведено полнотранскриптомное профилирование полученных моноцитов от больных раком молочной железы и здоровых женщин. Из полученных моноцитов in vitro были дифференцированы макрофаги. Проведена оценка способности полученных от макрофагов кондиционных сред влиять на апоптоз и пролиферацию клеток линии MDA-MB 231.Результаты. Показано, что транскриптомный профиль моноцитов больных РЖЖ имеет выраженные отличия по сравнению со здоровыми женщинами. Моноциты пациенток с раком молочной железы отличаются повышенной экспрессией мРНК белков-транспортеров ABCA1, ABCG1; хемокинов CCR1, CRRL2, CXCR4; факторов созревания и дифференцировки моноцитов Mafb и Jun; факторов, опосредующих эндоцитоз CD163, Siglec1; протеаз и тетраспонинов ADAM9, CD151, CD82 и ростового фактора HBEGF. Макрофаги, полученные в результате культивирования моноцитов больных раком молочной железы в условиях in vitro, продуцировали факторы, которые позволили поддерживать пролиферацию клеточной линии опухолевых клеток, чего не наблюдалось для моноцитов здоровых доноров.Заключение. Опухоль молочной железы оказывает системное влияние на моноциты периферической крови, программируя их к дифференцировке в макрофаги с проопухолевой функциональной активностью.

Astaxantin and Isoflavones Inhibit Benign Prostatic Hyperplasia in Rats by Reducing Oxidative Stress and Normalizing Ca/Mg Balance

Benign prostatic hyperplasia (BPH) is a common pathology among aging men. Despite the broad pharmacological interventions, the available remedies to treat BPH are yet not devoid of side effects. Herbal compounds are suggested to be an alternative option for the BPH treatment. In our study, we evaluated the effect of kudzu isoflavones and astaxanthin on the BPH animal model. The animals were randomly divided into five groups: control; testosterone-induced BPH group; and three BPH-induced groups, which received intragastrically for 28 days finasteride (5 mg/kg) as a positive control, isoflavones (200 mg/kg), and astaxanthin (25 mg/kg). BPH was induced by castration of animals and subsequent subcutaneous injections of prolonged testosterone (25 mg/kg). Prostate index and histology, biochemical parameters, and antioxidant activity were evaluated. A significant decrease in prostate weight, immunohistochemical markers, and normalization of prostate Ca/Mg ratio was found in all treatment groups. Astaxanthin treatment also resulted in decreased epithelial proliferation and normalized superoxide dismutase activity. In conclusion, both isoflavones and astaxanthin inhibited BPH development at a level comparable to finasteride in terms of prostate weight, prostatic epithelium proliferation, and prostate tissue cumulative histology score. These results suggest that isoflavones and especially astaxanthin could serve as a potential alternative therapy to treat BHP. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This research was funded by Russian Science Foundation, grant number 20-65-47025