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Introduction. Thermomechanical effects arising in heterogeneous composite materials under the influence of temperature significantly affect the strength and durability of structures made of them. These effects have a special influence on the thermal deformation of bridge and road structures under conditions of seasonal and daily changes in ambient temperature. They are caused by non-uniformity of the thermomechanical parameters of its fractions and fittings. Until now, the phenomenon of thermomechanical deformation of reinforced structures has not been sufficiently studied, therefore the tasks of their research are urgent. Problem Statement. The problem of the performed research is to establish the laws of thermomechanical deformation of composite materials (including cement concrete and asphalt concrete), which are reinforced with reinforcing rods, in the fields of variable temperatures. Purpose. The purpose of the work is to derive mathematical ratios that determine intrastructural thermal stresses in composites caused by variable temperature fields and heterogeneity of materials.

: Introduction: Kazakhstan has one of the fastest‐growing HIV epidemics in the world, with increasing rates among adolescents and young adults (AYA). Innovative strategies are needed to increase HIV testing uptake and decrease HIV stigma among AYA. Citizen science, defined as the active engagement of the general public in scientific research tasks, promotes and facilitates community engagement throughout the research process. This citizen science study used crowdsourcing to engage AYA in Kazakhstan to develop a digital intervention to reduce HIV stigma and promote HIV self‐testing. Our objectives in this paper are to describe the approach used, its feasibility and acceptability, and AYA motivations for and lessons learned collaborating on the study. Methods: From October 2021 to July 2022, in collaboration with a Community Collaborative Research Board and a Youth Advisory Board, we developed an open call requesting multimedia submissions to reduce HIV testing stigma. Eligible submissions were separated by age group (13−19 or 20−29 years) and judged by a panel composed of AYA (n = 23), healthcare professionals (n = 12), and representatives from the local government and non‐governmental organizations (n = 17). Each entry was reviewed by at least four judges and ranked on a 5‐point scale. The top 20 open call contestants were asked to submit self‐recordings sharing their motivation for and experience participating in the contest and lessons learned. Descriptive statistics were calculated for quantitative data. Qualitative data were coded using open coding. Results: We received 96 submissions from 77 youth across Kazakhstan. Roughly, three‐quarters (n = 75/96) of entries met judging eligibility criteria. Of the eligible entries, over half (n = 39/75) scored 3.5 or higher on a 5‐point scale (70.0%). The most frequent types of entries were video (n = 36/96, 37.5%), image (n = 28/96, 29.2%) and text (n = 24/96, 25.0%). AYA's primary motivations for collaborating on the study included a desire to improve society and help youth. The main challenges included creating content to address complex information using simple language, finding reliable information online and technological limitations. Conclusions: Crowdsourcing was feasible and highly acceptable among AYA in Kazakhstan. Citizen science approaches hold great promise for addressing the increasingly complex health and social challenges facing communities today., INTRODUCTION Eastern Europe and central Asia (EECA) has the world's fastest‐growing HIV epidemic with a 43.0% increase in incident cases of HIV acquisition from 2010 to 2020 [1] and for [...]

Abstract Introduction Kazakhstan has one of the fastest‐growing HIV epidemics in the world, with increasing rates among adolescents and young adults (AYA). Innovative strategies are needed to increase HIV testing uptake and decrease HIV stigma among AYA. Citizen science, defined as the active engagement of the general public in scientific research tasks, promotes and facilitates community engagement throughout the research process. This citizen science study used crowdsourcing to engage AYA in Kazakhstan to develop a digital intervention to reduce HIV stigma and promote HIV self‐testing. Our objectives in this paper are to describe the approach used, its feasibility and acceptability, and AYA motivations for and lessons learned collaborating on the study. Methods From October 2021 to July 2022, in collaboration with a Community Collaborative Research Board and a Youth Advisory Board, we developed an open call requesting multimedia submissions to reduce HIV testing stigma. Eligible submissions were separated by age group (13−19 or 20−29 years) and judged by a panel composed of AYA (n = 23), healthcare professionals (n = 12), and representatives from the local government and non‐governmental organizations (n = 17). Each entry was reviewed by at least four judges and ranked on a 5‐point scale. The top 20 open call contestants were asked to submit self‐recordings sharing their motivation for and experience participating in the contest and lessons learned. Descriptive statistics were calculated for quantitative data. Qualitative data were coded using open coding. Results We received 96 submissions from 77 youth across Kazakhstan. Roughly, three‐quarters (n = 75/96) of entries met judging eligibility criteria. Of the eligible entries, over half (n = 39/75) scored 3.5 or higher on a 5‐point scale (70.0%). The most frequent types of entries were video (n = 36/96, 37.5%), image (n = 28/96, 29.2%) and text (n = 24/96, 25.0%). AYA's primary motivations for collaborating on the study included a desire to improve society and help youth. The main challenges included creating content to address complex information using simple language, finding reliable information online and technological limitations. Conclusions Crowdsourcing was feasible and highly acceptable among AYA in Kazakhstan. Citizen science approaches hold great promise for addressing the increasingly complex health and social challenges facing communities today.

Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare’s milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare’s milk-derived exosomes as potential therapeutic carriers. Three extraction methods—immunoprecipitation, size exclusion chromatography, and total exosome isolation—were compared in terms of exosome characteristics, purity, and content. The isolated exosomes were then loaded with quercetin, and their ability to increase its bioavailability was tested in vitro and in vivo. Total exosome isolation was identified as the most efficient method for producing high-quality exosomes. These exosomes were loaded with quercetin and compared to free quercetin and exosomes alone. Exosomes loaded with 80 µM quercetin significantly restored β-galactosidase activity and cellular viability in doxorubicin-treated cells, exhibiting similar potency to 160 µM free quercetin. In aged model animals, treatment with quercetin-loaded exosomes resulted in significantly less acute and subacute damage to the myocardium, kidneys, and liver compared to untreated control animals. This study provides a proof-of-concept that mare’s milk-derived exosomes can be effectively absorbed by cells and animal tissues, supporting their potential use as drug carriers.

Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1H)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1H)-one (benzoyl-)isothiocyanates, and the corresponding thioureide derivatives 8-11a-c were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC50 for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives 8,9a-c, in contrast to their acetyl–(benzoyl) derivatives and 10,11a-c, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9a has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC50 = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9c has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC50 = 12,94 mM). Compounds 8a, 8b, and 9b showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC50 against α-glucosidase for compounds 8a, 8b, and 9b was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds 8c, 10a, 10b, 10c, 11a, 11b, and 11c did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1H)-ones are promising candidates for the further modification and study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models.

New effective wound healing agents are a priority for modern clinical pharmacology. A promising approach would be to develop medicinal products that promote angiogenesis, which is a critical step in wound healing. The aim of the study was to evaluate the wound healing effect of a medicinal product based on recombinant human angiogenin in gel form in various experimental models. Materials and methods: white outbred male rats were used as experimental ani mals. The study compared healing effects of a regenerating product containing recombinant human angiogenin (0.0025%) in gel form and a reference product in full-thickness excision, incision, and burn wound models. The healing effect of the test product in treating chronic wounds was assessed in a model of alloxan-induced diabetes mellitus. The anti-inflammatory effect of the test product containing recombinant human angiogenin was compared with that of another reference product in a model of adjuvant-induced arthritis. Results: according to the study, the test product based on recombinant human angiogenin exerts higher wound healing effect in treating excision, incision, and burn wounds than the reference product (Solcoseryl gel). Being applied, the test product intensifies tissue repair in chronic wounds in the model of alloxan-induced diabetes. The dissociation of necrotic tissues and the progression towards epithelialisation at wound edges are more rapid. The anti-inflammatory effect of the test product based on recombinant human angiogenin is comparable with that of the reference product (Diclofenac gel). Conclusions: the test product based on recombinant human angiogenin in gel form was found to have pronounced wound healing and anti-inflammatory effects comparable with those of reference products.

Pyridine derivatives still attract the attention of many researchers for their comprehensive biological research, possible promotion to the pharmaceutical market in order to be used as effective drugs. In this article, based on the well-known and fairly accessible in terms of laboratory synthesis of the 3-acetyl derivative of collidine, we carried out several simple chemical modifications to obtain new collidine derivatives not previously described. The structure of the synthesized compounds was confirmed by 1H- and 13C NMR spectroscopy. A biological screening of the synthesized compounds for hemorheological activity was carried out on an in vitro blood hyperviscosity model. It was shown that pronounced hemorheological activity was established for compounds 3, 4 and 5. Compound 4 also showed a pronounced antifibrotic effect in an experimental model of pulmonary fibrosis induced by intratracheal administration of bleomycin to rats. In an experimental model of pulmonary fibrosis in rats, the formation of a hyperviscosity syndrome was also observed, and blood viscosity decreased when compound 4 was administered to animals.

The phenomena of the formation of local defects and cracks in asphalt concrete pavements of roads and bridges are most often observed in climatic zones with large temperature differences during their seasonal and daily changes. To a large extent, this is due to the heterogeneity of the thermomechanical properties of the materials of the coating layers and the base. To prevent these phenomena, reinforcing rods and meshes are introduced into the coating structure. In this work, using the theory of thermoelasticity, it is shown by the method of mathematical modelling that in cases of incompatibility of the thermomechanical characteristics of asphalt concrete materials and reinforcement, additional localized thermal stresses arise in its small vicinity, which, even at moderate temperatures, can reach critical values and lead to local defects and cracks. Since these defects are latent, they cannot always be detected in practice. The presented results of analytic calculation validated these conclusions. They can be used in both road building and composite design.

The current study aims to evaluate potential hepatoprotective effect of lingonberry, cranberry and blueberry polyphenols on carbon tetrachloride (CCL-4)-induced acute and subacute liver injury in rats. A total of 55 male Wistar rats, divided into six experimental and control groups. With the exception of the negative control group, all groups received an intraperitoneal injection of CCl-4, twice a week for 14 days. An extract of lingonberry, cranberry, blueberry polyphenols and the positive control, silymarin were administered daily via intragastric route, for 14 consecutive days. The untreated control group showed characteristic of classical oxidative stress-mediated liver damage with vacuolization of the hepatocyte cytoplasm, infiltration by immune cells and proliferation of collagen fibers, decrease in body weight and increase in liver weight; increased levels of AST and ALT in serum, an increased lipid peroxidation in the liver. However, the use of cranberry and blueberry polyphenols significantly suppressed liver damage, exerting an effect comparable to the hepatoprotective effect of the positive control. The extracts prevented and reduced inflammatory liver damage by reducing IL-6, TNF-α and IFN-γ levels. In conclusion, blueberry and cranberry extracts have a protective effect against acute and subacute CCl4-induced hepatotoxicity in rats.

Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare's milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare's milk-derived exosomes as potential therapeutic carriers. Three extraction methods—immunoprecipitation, size exclusion chromatography, and total exosome isolation—were compared in terms of exosome characteristics, purity, and content. The isolated exosomes were then loaded with quercetin, and their ability to increase its bioavailability was tested in vitro and in vivo. Total exosome isolation was identified as the most efficient method for producing high-quality exosomes. These exosomes were loaded with quercetin and compared to free quercetin and exosomes alone. Exosomes loaded with 80 µM quercetin significantly restored β-galactosidase activity and cellular viability in doxorubicin-treated cells, exhibiting similar potency to 160 µM free quercetin. In aged model animals, treatment with quercetin-loaded exosomes resulted in significantly less acute and subacute damage to the myocardium, kidneys, and liver compared to untreated control animals. This study provides a proof-of-concept that mare's milk-derived exosomes can be effectively absorbed by cells and animal tissues, supporting their potential use as drug carriers. [ABSTRACT FROM AUTHOR]

The glucose-lowering drug metformin has been reported to have anticancer properties through unknown mechanisms. Other unknown factors that may influence its anticancer potential include the glycemic status of the patient. Therefore, the objective of this study is to determine the effect of different glucose environments on the antiproliferative potency and the cellular mechanism of action of metformin. Human breast cancer cells, MCF-7, were incubated in low, normal, elevated, and high glucose environments and treated with metformin. The antiproliferative potential of metformin and its effect on protein expression as well as its ability to induce cellular apoptosis and autophagy under different glucose environments, were determined using different molecular techniques. Metformin significantly inhibited cellular proliferation in a time- and glucose-concentration-dependent manner. In comparison to elevated glucose, low normal glucose alone induced a significant level of autophagy that was further increased in the presence of metformin. While glucose concentration did not appear to have an effect on the antiproliferative potency of metformin, the cellular basis of action was shown to be glucose-dependent. The antiproliferative mechanism of action of metformin in elevated and low normal glucose environments is mTOR-dependent, whereas, in the high glucose environment, the antiproliferative mechanism is independent of mTOR. This is the first study to report that both the antiproliferative potency and the cellular mechanism of action aredependent on the concentration of glucose.

Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1H)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1H)-one (benzoyl-)isothiocyanates, and the corresponding thioureide derivatives 8-11a-c were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC50 for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives 8,9a-c, in contrast to their acetyl–(benzoyl) derivatives and 10,11a-c, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9a has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC50 = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9c has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC50 = 12,94 mM). Compounds 8a, 8b, and 9b showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC50 against α-glucosidase for compounds 8a, 8b, and 9b was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds 8c, 10a, 10b, 10c, 11a, 11b, and 11c did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1H)-ones are promising candidates for the further modification and study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models. [ABSTRACT FROM AUTHOR]

Abstract Doxorubicin is a chemotherapeutic agent known to cause cardiotoxicity that is thought to be associated with oxidative stress. The aim of the current study is to investigate the role of grape polyphenols’ antioxidant property as cardioprotective against doxorubicin-induced cardiotoxicity. Adult Wistar rats weighing 200 ± 20 g were divided into 3 different groups: a doxorubicin group that received a single intraperitoneal administration of doxorubicin (8.0 mg/kg body weight), an experimental group that received doxorubicin and grape polyphenol concentrate (25 mg/kg) via intragastric route, and the third group was a negative control group that received water only. On day 8, blood samples and tissues were harvested for analyses. The results indicated that grape polyphenol concentrate was able to reduce the signs of cardiotoxicity of doxorubicin through the reduction of aspartate aminotransferase activation, increasing the plasma antioxidant levels and decreasing the level of free radicals. The results also showed that grape polyphenol concentrate was able to reverse doxorubicin-induced microscopic myocardial damage. The myocardial protective effect of grape polyphenol might likely be due to the increase in the level and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, grape polyphenol concentrate displayed cardioprotective effect and was able to reverse doxorubicin-induced-cardiomyopathy in experimental rats.

The aim of this study is determine the in vitro and in vivo antiradical properties and the cytoprotective activity of Allium nutans L. honey extract. The antiradical properties of the extracts were investigated in rabbit alveolar macrophages and human foreskin fibroblast (hFFs) cells in the presence of doxorubicin, a cytotoxic substance using DPPH and ABTS assays. The cytoprotective activities were determined using 18 Wistar rats divided into three different groups, a negative control, and two other groups with experimentally induced hepatotoxicity by a single intraperitoneal injection of 50% carbon tetrachloride (CCl4) oil solution. A positive control group, received drinking water only and an experimental group that was treated with Allium nutans L. honey extracts for 7 days. In vitro treatment with Allium nutans L. honey extracts resulted in 78% reduction in radical activity in DPPH and 91.6% inhibition using the ABTS. Also, honey extracts were able to preserve 100% of cell viability in the presence of the cytotoxic, doxorubicin. Furthermore, the treatment with honey extracts resulted in a significant reduction in damage to the structure of liver tissue, as well significant reduction in the levels of ALT and AST in the experimental group compared to the control group.

Application of culmiferous waste as fractionated strawy litter in the poultry plant under floor housing is considered. Optimal parameters of the initial culmiferous material processing by microwave radiation treatment are specified. Qualitative changes of structural straw surface are investigated.

Today, in connection with the development of surgical techniques, one of the main tasks is minimization of surgical trauma, reduction of postoperative complications and mortality, as well as the timing of hospital treatment of patients with maintained quality of surgical care. The widespread adoption of endoscopic surgery techniques into daily practice may help achieve the goal.Annually, we perform more than 450 laparoscopic surgeries for acute surgical diseases at the Institute, and we have performed more than 6,000 interventions since 2000. however, the laparoscopic method of surgery is not a priority, there are strict indications and contraindications, which we followed and thus avoided the development of iatrogenic complications associated with the use of this method for urgent diseases. Today, the laparoscopic technique is used in acute appendicitis, perforated gastric ulcer and duodenal ulcer, acute cholecystitis, strangulated hernia of the anterior abdominal wall, intestinal obstruction, as well as in patients with abdominal trauma. The use of the laparoscopic method in emergency abdominal surgery improves the quality of diagnosis and treatment, reduces the number of postoperative complications and mortality, as well as the time of treatment.

Abstract Enhancement of technology and techniques for drilling deep directed oil and gas bore hole is one of the most important problems of the current petroleum industry. Not infrequently, the drilling of these bore holes is attended by occurrence of extraordinary situations associated with technical accidents. Among these is the Eulerian loss of stability of a drill string in the channel of a curvilinear bore hole. Methods of computer simulation should play a dominant role in prediction of these states. In this paper, a new statement of the problem of critical buckling of the drill strings in 3D curvilinear bore holes is proposed. It is based on combined use of the theory of curvilinear elastic rods, Eulerian theory of stability, theory of channel surfaces, and methods of classical mechanics of systems with nonlinear constraints. It is noted that the stated problem is singularly perturbed and its solutions have the shapes of localized harmonic wavelets. The calculation results showed that the friction effects lead to essential redistribution of internal axial forces, as well as changing the eigenmode shapes and sites of their localization. These features make the buckling phenomena less predictable and raise the role of computer simulation of these effects.

The work presents evaluation of influence of plant preparation «Thyreoton-forte» on endothelium of vessels and morphological structure of thyroid gland in experimental hypothyreosis. Experimental hypothyreosis in rats was induced by administration of mercazolilum (10 mg/kg, intragastric introduction) during 28 days. The course administration of «Thyreoton-forte» (50,100 mg/kg, intragastric introduction) decreases the number of circulating endothelial cells (p < 0,05) and normalizes the structure of thyroid gland. Pharmacological effect of «Thyreoton-forte» is provided by protective influence in vascular endothelium and positive action on thyroid gland.