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Item Open Access MESENCHYMAL STEM CELLS COATED WITH SYNTHETIC BONE-TARGETING POLYMERS ENHANCE OSTEOPOROTIC BONE FRACTURE REGENERATION(MDPI AG, 2020-10-12) Safarova, Yuliya; Olzhayev, Farkhad; Umbayev, Bauyrzhan; Tsoy, Andrey; Hortelano, Gonzalo; Tokay, Tursonjan; Murata, Hironobu; Russell, Alan; Askarova, SholpanOsteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor cells (mesenchymal stem cells, MSCs). We investigated a new method of cell therapy with membrane-engineered MSCs to restore the osteoblast progenitor pool and to inhibit osteoclastic activity in the fractured osteoporotic bones. The primary active sites of the polymer are the N-hydroxysuccinimide and bisphosphonate groups that allow the polymer to covalently bind to the MSCs’ plasma membrane, target hydroxyapatite molecules on the bone surface and inhibit osteolysis. The therapeutic utility of the membrane-engineered MSCs was investigated in female rats with induced estrogen-dependent osteoporosis and ulnar fractures. The analysis of the bone density dynamics showed a 27.4% and 21.5% increase in bone density at 4 and 24 weeks after the osteotomy of the ulna in animals that received four transplantations of polymer-modified MSCs. The results of the intravital observations were confirmed by the post-mortem analysis of histological slices of the fracture zones. Therefore, this combined approach that involves polymer and cell transplantation shows promise and warrants further bio-safety and clinical exploration.Item Open Access PLANT EXTRACT OF LIMONIUM GMELINII ATTENUATES OXIDATIVE RESPONSES IN NEURONS, ASTROCYTES, AND CEREBRAL ENDOTHELIAL CELLS IN VITRO AND IMPROVES MOTOR FUNCTIONS OF RATS AFTER MIDDLE CEREBRAL ARTERY OCCLUSION(MDPI, 2021-11-15) Nurkenov, Tulendy; Tsoy, Andrey; Olzhayev, Farkhad; Abzhanova, Elvira; Turgambayeva, Anel; Zhussupova, Aizhan; Avula, Bharathi; Ross, Samir; Aituarova, Aigerim; Kassymova, Dariya; Zhusupova, Galiya; Shalakhmetova, Tamara; Tokay, Tursonjan; Lee, James C.; Askarova, SholpanThere are numerous publications demonstrating that plant polyphenols can reduce oxidative stress and inflammatory processes in the brain. In the present study we have investigated the neuroprotective effect of plant extract isolated from the roots of L. gmelinii since it contains a rich source of polyphenols and other biologically active compounds. We have applied an oxidative and inflammatory model induced by NMDA, H2O2 , and TNF-α in human primary neurons and astrocytes, and mouse cerebral endothelial cell (CECs) line in vitro. The levels of ROS generation, NADPH oxidase activation, P-selectin expression, and activity of ERK1/2 were evaluated by quantitative immunofluorescence analysis, confocal microscopy, and MAPK assay. In vivo, sensorimotor functions in rats with middle cerebral artery occlusion (MCAO) were assessed. In neurons NMDA induced overproduction of ROS, in astrocytes TNF-α initiated ROS generation, NADPH oxidase activation, and phosphorylation of ERK1/2. In CECs, the exposure by TNF-α induced oxidative stress and triggered the accumulation of P-selectin on the surface of the cells. In turn, pre-treatment of the cells with the extract of L. gmelinii suppressed oxidative stress in all cell types and pro-inflammatory responses in astrocytes and CECs. In vivo, the treatment with L. gmelinii extract improved motor activity in rats with MCAO. Keywords: antioxidants; neurons; astrocytes; CECs; L. gmelinii; plant polyphenolsItem Open Access GALACTOSE-INDUCED SKIN AGING: THE ROLE OF OXIDATIVE STRESS(Hindawi, 2020-06-17) Umbayev, Bauyrzhan; Askarova, Sholpan; Almabayeva, Aigul; Saliev, Timur; Masoud, Abdul-Razak; Bulanin, DenisSkin aging has been associated with a higher dietary intake of carbohydrates, particularly glucose and galactose. In fact, the carbohydrates are capable of damaging the skin’s vital components through nonenzymatic glycation, the covalent attachment of sugar to a protein, and subsequent production of advanced glycation end products (AGEs). This review is focused on the role of D-galactose in the development of skin aging and its relation to oxidative stress. The interest in this problem was dictated by recent findings that used in vitro and in vivo models. The review highlights the recent advances in the underlying molecular mechanisms of D-galactose-mediated cell senescence and cytotoxicity. We have also proposed the possible impact of galactosemia on skin aging and its clinical relevance. The understanding of molecular mechanisms of skin aging mediated by D-galactose can help dermatologists optimize methods for prevention and treatment of skin senescence and aging-related skin diseases.Item Open Access IMPROVEMENT OF NEUROLOGICAL FUNCTION IN RATS WITH ISCHEMIC STROKE BY ADIPOSEDERIVED PERICYTES(SAGE Publications, 2020-09-04) Ogay, Vyacheslav; Kumasheva, Venera; Li, Yelena; Mukhlis, Sholpan; Sekenova, Aliya; Olzhayev, Farkhad; Tsoy, Andrey; Umbayev, Baurzhan; Askarova, Sholpan; Shpekov, Azat; Kaliyev, Assylbek; Zhetpisbayev, Berik; Makhambetov, Yerbol; Akshulakov, Serik; Saparov, Arman; Ramankulov, YerlanPericytes possess high multipotent features and cell plasticity, and produce angiogenic and neurotrophic factors that indicate their high regenerative potential. The aim of this study was to investigate whether transplantation of adipose-derived pericytes can improve functional recovery and neurovascular plasticity after ischemic stroke in rats. Rat adipose-derived pericytes were isolated from subcutaneous adipose tissue by fluorescence-activated cell sorting. Adult male Wistar rats were subjected to 90 min of middle cerebral artery occlusion followed by intravenous injection of rat adipose-derived pericytes 24 h later. Functional recovery evaluations were performed at 1, 7, 14, and 28 days after injection of rat adipose-derived pericytes. Angiogenesis and neurogenesis were examined in rat brains using immunohistochemistry. It was observed that intravenous injection of adipose-derived pericytes significantly improved recovery of neurological function in rats with stroke compared to phosphate-buffered saline– treated controls. Immunohistochemical analysis revealed that the number of blood capillaries was significantly increased along the ischemic boundary zone of the cortex and striatum in stroke rats treated with adipose-derived pericytes. In addition, treatment with adipose-derived pericytes increased the number of doublecortin positive neuroblasts. Our data suggest that transplantation of adipose-derived pericytes can significantly improve the neurologic status and contribute to neurovascular remodeling in rats after ischemic stroke. These data provide a new insight for future cell therapies that aim to treat ischemic stroke patients.Item Open Access Mesenchymal stem cells modifications for enhanced bone targeting and bone regeneration(Future Medicine, 2020-04-16) Safarova, Yuliya; Umbayev, Bauyrzhan; Hortelano, Gonzalo; Askarova, SholpanIn pathological bone conditions (e.g., osteoporotic fractures or critical size bone defects), increasing the pool of osteoblast progenitor cells is a promising therapeutic approach to facilitate bone healing. Since mesenchymal stem cells (MSCs) give rise to the osteogenic lineage, a number of clinical trials investigated the potential of MSCs transplantation for bone regeneration. However, the engraftment of transplanted cells is often hindered by insufficient oxygen and nutrients supply and the tendency of MSCs to home to different sites of the body. In this review, we discuss various approaches of MSCs transplantation for bone regeneration including scaffold and hydrogel constructs, genetic modifications and surface engineering of the cell membrane aimed to improve homing and increase cell viability, proliferation and differentiation.Item Open Access ИЗУЧЕНИЕ ФЕНОЛЬНЫХ СОЕДИНЕНИЙ ЯГОД ТРЕХ ВИДОВ РАСТЕНИЙ РОДА VACCINIUM, ПРОИЗРАСТАЮЩИХ В ХАНТЫМАНСИЙСКОМ АВТОНОМНОМ ОКРУГЕ(Алтайский государственный университет, 2020-03-05) Gulyayev, Alexandr; Гуляев, Александр; Белова, Екатерина; Тритэк, Владислав; Шульгау, Зарина; Кривых, Елена; Коваленко, Людмила; Дренин, Алексей; Ботиров, ЭркинВпервые проведено исследование химического состава полифенольных соединений плодов клюквы (Vaccinium oxycoccus L.), черники (Vaccinium myrtillus L.) и брусники (Vaccinium vitis-idaea L.), произрастающих на территории Сургутского района Ханты-Мансийского автономного округа – Югры. Свежие ягоды пятикратно экстрагировали 80%-ной водно-спиртовой смесью при комнатной температуре. Полученные экстракты объединяли, фильтровали, растворитель из фильтрата отгоняли под вакуумом на ротационном испарителе. В составе полученных экстрактов методом ВЭЖХ идентифицировано 15 гликозидов антоцианидинов, а также 30 фенольных соединений, относящихся к гидроксибензойным и гидроксикоричным кислотам, флавонолам, катехинам и процианидинам. Идентификация фенольных соединений проводилась в соответствии с временами удерживания и спектрами поглощения соответствующих аналитических стандартов. Основным фенольным соединением экстракта ягод клюквы является хлорогеновая кислота. Установлен рост содержания полифенолов в ряду: клюква–брусника–черника. Полученные данные в целом по содержанию полифенолов сопоставимы с результатами исследования клюквы и черники из региона Аляски, несущественно отличаясь по содержанию антоцианов и отдельных флавонов. Значительные отличия по фенольным компонентам выявляются при сравнении наших данных с литературными данными по бруснике и клюкве из районов севера и востока Европы (Польша, Белоруссия, Норвегия). Обнаруженные количественные различия по отдельным полифенолам, вероятно, связаны с географическими и местными природными условиями. Высокое содержание полифенолов в изученных нами ягодах позволяет предполагать возможность использования их в качестве фармацевтического сырья.Item Open Access The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease(Frontiers Media, 2020-03-18) Askarova, Sholpan; Umbayev, Bauyrzhan; Masoud, Abdul-Razak; Kaiyrlykyzy, Aiym; Safarova, Yuliya; Tsoy, Andrey; Olzhayev, Farkhad; Kushugulova, Almagul R.Gut microbiome is a community of microorganisms in the gastrointestinal tract. These bacteria have a tremendous impact on the human physiology in healthy individuals and during an illness. Intestinal microbiome can influence one's health either directly by secreting biologically active substances such as vitamins, essential amino acids, lipids et cetera or indirectly by modulating metabolic processes and the immune system. In recent years considerable information has been accumulated on the relationship between gut microbiome and brain functions. Moreover, significant quantitative and qualitative changes of gut microbiome have been reported in patients with Alzheimer's disease. On the other hand, gut microbiome is highly sensitive to negative external lifestyle aspects, such as diet, sleep deprivation, circadian rhythm disturbance, chronic noise, and sedentary behavior, which are also considered as important risk factors for the development of sporadic Alzheimer's disease. In this regard, this review is focused on analyzing the links between gut microbiome, modern lifestyle, aging, and Alzheimer's disease.Item Open Access Статины: потенциал в лечении болезни альцгеймера(Al-Farabi Kazakh National University, 2015-04) Askarova, S.; Adambekov, S.; Tsoy, A.; Isayeva, R.; Shalakhmetova, T.Болезнь Альцгеймера (БА) является широко распространённым хроническим нейродегенеративным заболеванием, поражающим людей в возрасте 65 лет и старше, против которого до сих пор не разработано эффективных методов лечения. Данные эпидемиологических исследований свидетельствуют о том, что долговременное применение гиполиподемических препаратов статинов снижает риск развития болезни Альцгеймера.Item Metadata only Engineering of cell membranes with a bisphosphonate-containing polymer using ATRP synthesis for bone targeting(2014-11-01) D'Souza, Sonia; Murata, Hironobu; Jose, Moncy V.; Askarova, Sholpan; Yantsen, Yuliya; Andersen, Jill D.; Edington, Collin D.J.; Clafshenkel, William P.; Koepsel, Richard R.; Russell, Alan J.; Sonia, D'SouzaAbstract The field of polymer-based membrane engineering has expanded since we first demonstrated the reaction of N-hydroxysuccinimide ester-terminated polymers with cells and tissues almost two decades ago. One remaining obstacle, especially for conjugation of polymers to cells, has been that exquisite control over polymer structure and functionality has not been used to influence the behavior of cells. Herein, we describe a multifunctional atom transfer radical polymerization initiator and its use to synthesize water-soluble polymers that are modified with bisphosphonate side chains and then covalently bound to the surface of live cells. The polymers contained between 1.7 and 3.1 bisphosphonates per chain and were shown to bind to hydroxyapatite crystals with kinetics similar to free bisphosphonate binding. We engineered the membranes of both HL-60 cells and mesenchymal stem cells in order to impart polymer-guided bone adhesion properties on the cells. Covalent coupling of the polymer to the non-adherent HL-60 cell line or mesenchymal stem cells was non-toxic by proliferation assays and enhanced the binding of these cells to bone.Item Open Access Eag1 K+ Channel: Endogenous Regulation and Functions in Nervous System(Oxidative Medicine and Cellular Longevity, 2017-03-06) Han, Bo; Tokay, Tursonjan; Zhang, Guangming; Sun, Peng; Hou, ShangweiEther-a-go-go ` 1 (Eag1, Kv10.1, KCNH1) K+ channel is a member of the voltage-gated K+ channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K+ channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated. The present review will focus on the recent progress on the channel regulation by endogenous signals and the potential functions of EAG1 channels in normal neuronal signaling as well as neurological diseases.Item Open Access Клеточные технологии в трансплантации почки / Cell technologies in renal transplantation(Нефрология и диализ, 2014-04) Momynaliev (Момыналиев), K.T. (К.Т.); Ogay (Огай), Vyacheslav (Вячеслав); Khoroshun (Хорошун), E.V. (Е.В.); Babenko (Бабенко), N.N. (Н.Н.); Kaabak (Каабак), М.М. (M.M.)местительной терапии при хронической почечной недостаточности в терминальной стадии. Благодаря современным иммунодепрессантам, резко повысилась краткосрочная выживаемость пациентов и трансплантата. Однако долгосрочная выживаемость аллотрансплантата почки не улучшается такими же темпами. Хроническая нефропатия аллотрансплантата остается наиболее частой причиной потери трансплантата, тогда как сердечно-сосудистые заболевания остаются ведущей причиной смертности пациентов после трансплантации... Currently, renal transplantation has firmly established as the main method of replacement therapy in patients with the end stage chronic renal disease. Thanks to modern immunosuppressive drugs, shortterm graft and patient survival are dramatically increased. However, long-term renal allograft survival has improved in a lesser extent. Chronic allograft nephropathy is the most common cause of graft failure, whereas cardiovascular diseases remain the leading cause of death among patients receiving renal transplantation. To improve the results of transplantation, it is important to continue developing new strategies for the prevention of acute and chronic rejection...Item Open Access Саморегуляция раковых стволовых клеток толстой кишки / Colon cancer stem cells self regulation(Вестник КазНУ. Серия биологическая. №1/1 (60). 2014, 2014) Ogay (Огай), Vyacheslav (Вячеслав)Colon cancer high death rate and low percentage of recovery depend on tumor initiating cancer stem cells (CSCs). CSCs have ability such as survival in stress condition, absence of sensitivity to apoptose. These properties CSCs can regulate by autocrine way. In our work it was created data base of colon CSCs autocrine inductors. Understanding of CSCs protection mechanisms help to develop effective elimination methods of these cells. Высокая смертность от рака толстой кишки и низкий процент полного выздоровления от рака связаны с сущетвованием опухоль инициирующих раковых стволовых клеток (РСК). РСК обладают такими свойствами как выживаемость, отсутствие чувствительности к апоптозу. Эти свойства РСК способны регулировать аутокринным путем. В нашей работе была создана база данных по аутокринным стимуляторам РСК толстой кишки. Понимание защитных механизмов РСК поможет разработать эффективные методы элиминации этих клеток.Item Open Access Паракринные регуляторы раковых стволовых клеток толстой кишки / Paracrine regulators of colon cancer stem cells(Вестник КазНУ. Серия биологическая, 2014) Ogay (Огай), Vyacheslav (Вячеслав); Issabekova (Исабекова), A.S. (А.С.)Раковые стволовые клетки основная причина возобновления болезни после лечения. Для эффективной борьбы с этими клетками необходимо понимание механизмов выживание этих клеток и их стимуляторов. В данной работе оценено влияние микроокружение опухоли на рост и поддержание опухоли. Основными модуляторами раковых стволовых клеток являются опухоль ассоциированные миофибробласты и макрофаги, а также Th17 клетки. Cancer stem cells are main cause of cancer recurrence. For effective treatment it is necessary to understand haw survive and stimulate these cells. In this work it was estimated influence of cancer microenvironment to growth and surveillance of cancer. The main modulators of cancer are cancer associated miofibroblasts and macrophages, and also Th17 cells.Item Open Access Bonghan Ducts as Possible Pathways for Cancer Metastasis(Journal of Acupuncture and Meridian Studies, 2009-04-01) Yoo, Jung Sun; Kim, Hong Bae; Ogay, Vyacheslav; Lee, Byung-Cheon; Ahn, Saeyoung; Soh, Kwang-supObjective: The present study has been designed to find a possible new route for the metastasis of cancer cells on the fascia surrounding tumor tissue using a novel technique of trypan blue staining. Materials and Methods: Tumor tissues were grown in the skin of nude mice after subcutaneous inoculation with human lung cancer cells. Trypan blue was recently identified as a dye with specificity for Bonghan ducts (BHDs) and not other tissues, such as blood or lymph vessels or nerves. Results: We demonstrate that the trypan blue staining technique allows the first visualization of BHDs which are connected to tumor tissues.Item Open Access Visualization of Bonghan Microcells by Electron and Atomic Force Microscopy(Journal of Acupuncture and Meridian Studies, 2009-04-13) Baik, Ku Youn; Ogay, Vyacheslav; Jeoung, Sae Chae; Soh, Kwang-supObjectives: The origin of adult stem cells remains an open question. If they derive from embryos, it is difficult to determine the mechanism which interrupts their differentiation during tissue formation. In the 1960s, the Bonghan microcell was suggested as one possible, yet to be described, route of stem cell production, such that they have the potential to proliferate to produce normal cells. Materials and Methods: In this study, Bonghan microcells were isolated from Bonghan tissues on rat organ surfaces, and their detailed morphology examined by electron and atomic force microscopy. Results: The ultrastructure observed distinguished them from apoptotic bodies and other microorganisms, and their unique, possible proliferation feature, as protruding threads, was imaged by atomic force microscopy.Item Open Access Comparison of the characteristic features of bonghan ducts, blood and lymphatic capillaries(Journal of Acupuncture and Meridian Studies, 2009-03-31) Ogay, Vyacheslav; Bae, Kyung Hee; Kim, Ki Woo; Soh, Kwang-supObjective: To show that the characteristic morphological and ultrastructural features of a Bonghan corpuscle and duct presented here are consistent with the description given in the early reports of Bonghan Kim. Materials and Methods: We compared the morphological aspects of Bonghan ducts with those of blood and lymphatic capillaries on the ultrastructural level to display the manifestly distinctive nature of the Bonghan system. Results: The walls of the ductules were observed to be composed of a single layer of endothelial cells with characteristic rod-shaped nuclei and were not surrounded by a basal lamina or by accessory cells, such as pericytes or smooth muscle cells. The abluminal cell membranes of Bonghan ductules were not attached by anchoring filaments to the fibers of extracellular matrices as observed in lymphatic capillaries.Item Open Access Electrical сharacterization of proposed transpositional acupoints on the Urinary Bladder Meridian in a Rat Model(Hindawi Publishing Corporation. Evidence-Based Complementary and Alternative Medicine., 2011) Han, Hyun-Jung; Park, Sang-Jun; Soh, Kwang-sup; Myoung, Hyoun-Seok; Lee, Kyoung-Joung; Ogay, Vyacheslav; Lee, Yong-HeumSpecific electrical characteristicsof acupointswere investigated on the urinary bladder (BL) meridian in 14 rats. BL acupointsand non-acupoints on the back were selected and their electrical voltages were measured by using aSPACsystem.The mean voltages of each point or each line were statistically analyzed by using the ANOVA test...Item Open Access First experience of using biological prosthesis "UniLine" for correction of heart valve diseases(Personalized medicine and Global Health, 2015) Zhurko, S.; Olzhayev, F.; Chiginev, V.; Fedorov, S.To conduct a clinical study of immediate results, assessment of hemodynamic characteristics of developed a new biological stented prosthesis «UniLine» (Russia, Kemerovo) designed for correction of heart valve lesions of various etiologies.Item Open Access Perinatal outcomes in preterm premature rupture of membranes(Personalized medicine and Global Health, 2015) Chuvakova, T.; Bapayeva, G.; Issayeva, R.; Begimbetova, D.; Olzhayev, F.; Dzhamanaeva, K.; Kenbaeva, K.Preterm premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity and mortality. Intrauterine continuous amnioinfusion via a subcutaneously implanted port system for PPROM is an attempt to improve the perinatal outcomes.Item Open Access Evaluation of amino acid level in the blood of fetuses and newborns with intrauterine growth restriction(Personalized medicine and Global Health, 2015) Chuvakova, T.; Bapayeva, G.; Issayeva, R.; Olzhayev, F.; Dzhamanaeva, K.; Kenbaeva, K.The processes of growth of the fetus are provided by a constant supply of amino acids from mother, which provides the production of proteins and muscle tissue of the fetus. The purpose of this research was to study the amino acid level in blood of fetuses and newborns with intrauterine growth restriction.
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