Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia.

peer reviewedCurrently, the role of the neurotrophic factors BDNF and GDNF in maintaining the brain's resistance to the damaging effects of hypoxia and functional recovery of neural networks after exposure to damaging factors are actively studied. The assessment of the effect of an increase in the level of these neurotrophic factors in brain tissues using genetic engineering methods on the resistance of laboratory animals to hypoxia may pave the way for the future clinical use of neurotrophic factors BDNF and GDNF in the treatment of hypoxic damage. This study aimed to evaluate the antihypoxic and neuroprotective properties of BDNF and GDNF expression level increase using adeno-associated viral vectors in modeling hypoxia in vivo. To achieve overexpression of neurotrophic factors in the central nervous system's cells, viral constructs were injected into the brain ventricles of newborn male C57Bl6 (P0) mice. Acute hypobaric hypoxia was modeled on the 30th day after the injection of viral vectors. Survival, cognitive, and mnestic functions in the late post-hypoxic period were tested. Evaluation of growth and weight characteristics and the neurological status of animals showed that the overexpression of neurotrophic factors does not affect the development of mice. It was found that the use of adeno-associated viral vectors increased the survival rate of male mice under hypoxic conditions. The present study indicates that the neurotrophic factors' overexpression, induced by the specially developed viral constructs carrying the BDNF and GDNF genes, is a prospective neuroprotection method, increasing the survival rate of animals after hypoxic injury

ИЗОТОПНЫЕ ОТНОШЕНИЯ СТРОНЦИЯ 87Sr/86Sr В ВОДЕ РЯДА РЕК ЮЖНОГО УРАЛА

87Sr/86Sr isotopic ratios are widely used to identify strontium sources and study strontium behaviour in(bio)geochemical cycles. 87Sr/86Sr in surface waters can reflect the average composition of bioavailable (i.e. available forfurther absorption by plants and animals) strontium in the catchment specific area. Based on those 87Sr/86Sr ratios, theregional maps of the bioavailable strontium distribution (strontium isoscapes) can be compiled. A complex block structurecharacterizes the Ural mountain system. Individual parts (blocks) are composed of rocks of various ages, genesis andgeochemical characteristics, which can radically change at a distance of several tens of kilometres. Such variability wouldbe reflected in strontium isotopic ratios, thus making it possible to determine the local isotopic signatures of bioavailablestrontium.This work aimed to study 87Sr/86Sr in the water in the rivers of the Southern Urals. We determined the contents andisotopic ratios of strontium in river water samples collected from the territories of the Orenburg and Chelyabinsk regionsand the Republic of Bashkortostan in 2019–2020.For the first time in the surface water of the rivers in the Southern Urals (Ural, Belaya, Tobol, Karagaily-Ayat, Sim, andothers), the 87Sr/86Sr isotopic ratios have been determined, and their variations have been analyzed. 87Sr/86Sr values varyin the range 0.70666–0.71063 (average 0.70908) for the rivers of the Urals basin, 0.70749–0.71058 (average 0.70924)for the Kama-Volga basin, 0.70946–0.71176 (average 0.71071) for the Tobol basin. Such features of the strontium isotopiccomposition may be due to the influence of underlying rocks of the catchment area drained by river water. The dataobtained can be used to identify the sources of strontium input into the water system during hydrological and environmentalstudies; to confirm the authenticity of food products of plant and animal origin; to carry out comparisons in thestudies of the migration of ancient people and animals, as well as to determine the raw material areas for the productionof vegetable and woollen textiles and wooden products in antiquity.Изотопные отношения стронция 87Sr/86Sr широко используются для выявления источниковстронция и исследования его поведения в (био)геохимических циклах, а в поверхностных водах они могут отражатьусредненный состав биодоступного (доступного для дальнейшего поглощения растениями и животными)стронция на конкретной территории водосбора, на основании чего могут быть составлены региональные картыраспределения биодоступного стронция (Sr изоскейпы). Уральская горная система характеризуется блочнойструктурой, отдельные части (блоки) которой сложены разнообразными по возрасту, генезису и геохимическимособенностям горными породами, которые могут радикально изменяться на расстоянии нескольких десятковкилометров. Такая вариативность будет отражаться и в изотопных отношениях стронция, что позволит с достаточновысокой точностью определить локальные метки биодоступного стронция.Целью работы являлось исследование изотопных отношений стронция 87Sr/86Srв воде ряда рек Южного Урала.В образцах речной воды, отобранных в 2019–2020 гг. с территорий Оренбургской и Челябинской областей и РеспубликиБашкортостан, определены содержания (квадрупольная масс-спектрометрия с индуктивно связаннойплазмой) и изотопные отношения стронция (мультиколлекторная масс-спектрометрия с индуктивно связаннойплазмой и термоионизационная масс-спектрометрия после хроматографического выделения стронция).Впервые в поверхностной воде ряда рек Южного Урала (Урал, Белая, Тобол, Карагайлы-Аят, Сим и др.) определеныизотопные отношения 87Sr/86Sr и проанализированы их вариации. Для рек бассейна р. Урал значения87Sr/86Sr варьируются в диапазоне 0.70666–0.71063 (среднее 0.70908), для бассейна р. Кама – 0.70749–0.71058(среднее 0.70924), для бассейна р. Тобол – 0.70946–0.71176 (среднее 0.71071). Подобные особенности изотопногосостава стронция могут быть обусловлены типом подстилающих горных пород водосбора, дренируемых речнойводой. Полученные данные могут быть использованы для выявления источников поступления стронция в воднуюсистему при гидрологических и экологических исследованиях, для подтверждения аутентичности пищевыхпродуктов растительного и животного происхождения, для проведения сопоставлений при исследованияхмиграций древних людей и животных, а также для определения сырьевых ареалов для производства растительногои шерстяного текстиля, деревянных изделий в древности

DEVELOPMENT OF THE SOFTWARE ARCHITECTURE OF A UNIVERSAL SYS- TEM THERMAL IMAGING DIAGNOSTICS

Formation of requirements and the development of the software architecture of a universal system thermal imaging diagnostics. Description of the basic algorithms of the system

MATHEMATICAL MODELING OF HEATING AND COOLING OF SAUSAGES

In the article the mathematical modeling of the processes of heating and cooling of sausage products in order to define reference characteristics of the processes was carried out. Basic regularities of the processes are graphically shown

RESEARCH OF NETWORK MANAGEMENT SYSTEMS AND DEVELOPMENT OF STRUCTURE OF INFORMATION SUPPORT SYSTEMS DIAGNOSTICS, MONITORING AND CONTROL OF INDUSTRIAL OBJECTS

The article presents research of network energy management systems in buildings and constructions that show the possibility of use the Ethernet networks. The platform and aids implementation monitoring and energy management are chosen, database structure a high level of abstraction and a generalized block diagram are proposed

⁸⁷Sr/⁸⁶Sr ISOTOPE RATIOS IN THE RIVER WATERS OF THE SOUTHERN URALS

87Sr/86Sr isotopic ratios are widely used to identify strontium sources and study strontium behaviour in(bio)geochemical cycles. 87Sr/86Sr in surface waters can reflect the average composition of bioavailable (i.e. available forfurther absorption by plants and animals) strontium in the catchment specific area. Based on those 87Sr/86Sr ratios, theregional maps of the bioavailable strontium distribution (strontium isoscapes) can be compiled. A complex block structurecharacterizes the Ural mountain system. Individual parts (blocks) are composed of rocks of various ages, genesis andgeochemical characteristics, which can radically change at a distance of several tens of kilometres. Such variability wouldbe reflected in strontium isotopic ratios, thus making it possible to determine the local isotopic signatures of bioavailablestrontium.This work aimed to study 87Sr/86Sr in the water in the rivers of the Southern Urals. We determined the contents andisotopic ratios of strontium in river water samples collected from the territories of the Orenburg and Chelyabinsk regionsand the Republic of Bashkortostan in 2019–2020.For the first time in the surface water of the rivers in the Southern Urals (Ural, Belaya, Tobol, Karagaily-Ayat, Sim, andothers), the 87Sr/86Sr isotopic ratios have been determined, and their variations have been analyzed. 87Sr/86Sr values varyin the range 0.70666–0.71063 (average 0.70908) for the rivers of the Urals basin, 0.70749–0.71058 (average 0.70924)for the Kama-Volga basin, 0.70946–0.71176 (average 0.71071) for the Tobol basin. Such features of the strontium isotopiccomposition may be due to the influence of underlying rocks of the catchment area drained by river water. The dataobtained can be used to identify the sources of strontium input into the water system during hydrological and environmentalstudies; to confirm the authenticity of food products of plant and animal origin; to carry out comparisons in thestudies of the migration of ancient people and animals, as well as to determine the raw material areas for the productionof vegetable and woollen textiles and wooden products in antiquity

Effects of SRC and IKKβ Kinase Inhibition in Ischemic Factors Modeling In Vitro and In Vivo

The search for new molecular targets whose modulation can reduce nerve cell dysfunction and neuronal death during ischemic damage is one of the most significant issues in both fundamental and clinical neurobiology. Various kinase enzymes are often considered to be such promising targets since they are involved in key molecular cascades that regulate cell adaptation to stress factors. Our work is devoted to the study of the role of two kinases—SRC and IKKβ—in maintaining the neural networks’ functional activity under a hypoxic condition in vivo and in vitro. SRC kinase is a cytoplasmic non-receptor protein tyrosine kinase. It is involved in the regulation of cell proliferation and differentiation; its expression in nerve cells changes during hypoxia. IKKβ kinase is involved in the regulation of the activity of the transcription factor NF-κB, which is a pleiotropic regulator of many cellular signaling pathways. We have shown that blockade of SRC and IKKβ kinases by selective inhibitors maintains cell viability in modeling hypoxic damage in vitro but does not allow for the preservation of the bioelectrical activity of neurons. Studies in vivo have shown the neuroprotective effect of SRC but not IKKβ kinase inhibition in the modeling of cerebral ischemia in mice

COVID-19 biobank: features of the cytokine profile

Aim. Using a collection of samples from the biobank ofCityHospital № 40 ofSt. Petersburg, to study the cytokine profile in patients with coronavirus disease 2019 (COVID-19) and sepsis, in comparison with patients with abdominal inflammation and septicemia.Material and methods. The study included serum samples from 181 patients with sepsis and COVID-19 (127 patients with a diagnosis confirmed by polymerase chain reaction (PCR); 54 patients with a negative PCR test, but with a characteristic computed tomographic lung performance) and 47 patients with abdominal sepsis. The content of cytokines was determined using a multiplex immunofluorescence analysis based on the Luminex xMAP technology using the HCYTOMAG60K panel — a soluble CD40 ligand (sCD40L), interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNFα), vascular endothelial growth factor (VEGF). Other laboratory parameters (C-reactive protein (CRP), ferritin, procalcitonin) were taken from patient records. Normality of distribution was assessed by the Shapiro-Wilk test. To compare groups, the Mann-Whitney test for independent samples, Wilcoxon test for dependent samples, and the Kruskal-Wallis test with Bonferroni correction for multiple comparisons were used.Results. In patients with sepsis and COVID-19 infection, no differences in the concentrations of cytokines, ferritin and CRP were found between the groups with detected and not detected virus by PCR test. Based on this, this group was considered homogeneous when studying the cytokine profile. It was shown that in patients with sepsis and COVID-19, significantly higher levels of sCD40L (p<0,0001) and VEGF (p=0,037) and relatively low levels of CRP (p<0,0001), IL-6 (p<0,0001), IL-8 (p<0,0001), TNFα (p<0,00058).Conclusion. These results indicate that sepsis in patients with COVID-19 courses with less elevation in inflammatory cytokine than in abdominal sepsis. At the same time, a critically high level of sCD40L indicates the significant endothelial damage

Related expression of TRKA and P75 receptors and the changing copy number of MYC-oncogenes determine the sensitivity of brain tumor cells to the treatment of the nerve growth factor in combination with cisplatin and temozolomide

Oncological diseases are an urgent medical and social problem. The chemotherapy induces not only the death of the tumor cells but also contributes to the development of their multidrug resistance and death of the healthy cells and tissues. In this regard, the search for the new pharmacological substances with anticancer activity against drug-resistant tumors is of utmost importance. In the present study we primarily investigated the correlation between the expression of TrkA and p75 receptors with the nerve growth factor (NGF) and cisplatin or temozolomide sensitivity of anaplastic astrocytoma (AA), glioblastoma (GB) and medulloblastoma (MB) cell cultures. We then evaluated the changing of copy numbers of MYCC and MYCN and its correlation with cytotoxicity index (CI) in MB cells under NGF exposition. The primary cell cultures were obtained from the tumor biopsy samples of the patients with AA (n=5), GB (n=7) or MB (n=25) prior to radiotherapy and chemotherapy. The cytotoxicity effect of NGF and its combinations with cisplatin or temozolomide, the relative expression of TrkA and p75 receptors, its correlations with CI in AA, GB and MB primary cell cultures were studied by trypan blue cytotoxicity assay and immunofluorescence staining respectively. The effect of NGF on MYCC and MYCN copy numbers in MB cell cultures was studied by fluorescence in situ hybridization. We found that the expression of TrkA and p75 receptors (p=0.03) and its ratio (p=0.0004) depends on the sensitivity of AA and GB cells to treatment with NGF and its combinations with cisplatin or temozolomide. NGF reduces (p<0.05) the quantity of MB cells with six or eight copies of MYCN and three or eight copies of MYCC. Besides, NGF increases (p<0.05) the quantity of MB cells containing two copies of both oncogenes. The negative correlation (r=-0.65, p<0.0001) is established between MYCC average copy numbers and CI of NGF in MB cells. The relative expression of NGF receptors (TrkA/p75) and its correlation with CI of NGF and its combinations in AA and GB cells point to the mechanism involving a cell death signaling pathway. NGF downregulates (p<0.05) some increased copy numbers of MYCC and MYCN in the human MB cell cultures, and upregulates normal two copies of both oncogenes (p<0.05)