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THE STUDY OF THE HISTORY OF THE GREAT SIAMESE OF BUKHARA
No full text<p><i>This article contains information about the history of several siymos who lived and worked in Bukhara and their contributions to the development of the field of education and science.</i></p>
FACTORS ENSURING THE PRIORITY OF FAMILY EDUCATION AMONG STUDENTS
No full text<p><i> In this article, pedagogical and psychological features of preparing students for social family life, as well as giving importance to spiritual environment and moral issues in families, ways of reaching maturity based on the traditions of one's nation and universal values, and the factors of ensuring the priority of family education in student youth are described.</i></p>
Crosstalk between Glia Cells and Neurons under the Influence of Paclitaxel: Novel Insights into the ‘Chemobrain’?
Get PDFAfter chemotherapy, some patients develop long-lasting cognitive impairments, a condition known as ‘chemobrain’. Patients with chemobrain may suffer from memory impairment, poor concentration, slow processing speed, and dysarthria, thus dramatically deteriorating the quality of life of affected patients. Chemobrain can occur in up to 75 % of patients receiving adjuvant chemotherapy, and therefore its understanding has become an important and indispensable task in science and medicine. Studies showed that paclitaxel, a taxane that is used in ovarian-, breast, and prostate-cancer can induce neurodegeneration and potentially cause the chemobrain condition. Paclitaxel as an antineoplastic drug alters cell proliferation and mitosis rate of tumour cells. It stabilises the microtubule organisation by binding directly to β-tubulins and, thus, supresses depolymerization. Despite the actual function of paclitaxel to eliminate tumour cells by apoptosis, healthy cells such as sensory neurons of the dorsal root ganglion can be affected as well, leading to peripheral neuropathy. Studies showed that paclitaxel can lead to cytokine and chemokine release of macrophages into the dorsal root ganglia and hence, inducing inflammation. Moreover, it was shown in vitro that paclitaxel also exerts diverse changes in primary astrocytes and microglia.
In the healthy brain, astrocytes fulfil a multitude of functions. Most importantly, astrocytes are of great importance for the maintenance of neuronal functionality. They create the blood-brain barrier, regulate the homeostatic milieu in the extracellular space, and are responsible for the active removal of neurotransmitters in the synaptic cleft. Importantly, astrocytes maintain the brains functions by supporting their surrounding cell entities. Another important group of glia residing the central nervous system (CNS) are microglia, acting as immunocompetent cells. Microglia are phagocytes and remove remains of dead and degenerated neurons and glia cells, and thus also contribute to the maintenance of neuronal functionality.
To unravel the roles of astrocytes and microglia during healthy and pathological state induced by paclitaxel stimulation, diverse experiments on molecular and cellular levels were conducted with primary derived rat glia cells. For investigating the effect of glia on the functionality of neurons, the conditioned media of differently treated astrocytes, microglia and both together in co-culture were used for stimulation of cortical neurons. Functional changes were investigated by morphological and electrophysiological analyses. Transcriptomic analysis of paclitaxel treated astrocytes enabled the profiling of important genes modulated under pathological environments induced by paclitaxel.
Data revealed that paclitaxel-exposed primary astrocytes displayed an altered cytokine expression profile and up-regulated the release of neurotrophic substances like BDNF and NT 3. Microglia, on the other hand, responded to paclitaxel by releasing pro-inflammatory cytokines. However, these effects were more or less compensated when astrocytes and microglia were cultivated together.
Transcriptomic analysis of untreated astrocytes and astrocytes treated with 1 µM paclitaxel confirmed previous data and highlight the importance of astrocytes under pathological conditions. Astrocytes underwent stimulation with paclitaxel showed upregulation in the expression of genes important for tubulin formation. This finding verified the antineoplastic effect of paclitaxel and approved structural changes of cells in the central nervous system being potentially involved in the emergence of chemotherapy-induced cognitive impairments. A highly promising finding was the upregulation of relevant growth factors. Consistent, to RT qPCR data neurotrophic factors are significantly overexpressed after paclitaxel-exposure, making astrocytes an attractive target for cancer treatment in future by offering support of neuronal maintenance. Further important changes were identified in genes for cell cycle DNA replication, astrocyte development, glutamate receptor activity, and reactive oxygen species comparing healthy and pathological astrocytes.
Furthermore, to investigate the inter-cellular communication of astrocytes and microglia that were exposed to paclitaxel with neurons, we collected the conditioned media of paclitaxel treated glia. Neuronal cultures were exposed to glia conditioned media, and we investigated the neuronal morphology as well as their activity using Multi-Electrode-Arrays (MEA) and the expression of Ca2+-channels and diverse synapses. While the conditioned media of healthy astrocytes increased neuronal activity maintaining their morphology, the conditioned media of paclitaxel-treated astrocytes led to decreases neuronal activity and impaired the ramification of primary neurons in vitro. Opposite effects were seen for microglia. Healthy microglia had negative effects on the length and number of neuronal outgrowths. Neuronal activity was first decreased and then rose again within time after addition of the healthy microglial conditioned media, while paclitaxel-treated microglia acutely increased the spike rate of cortical neurons. Moreover, data showed that the conditioned media of glia differentially modulated the expression of pre- and postsynaptic markers, when glia were treated with paclitaxel being a potential reason for changes in neuronal activity. However, the expression profile of Ca2+ channels remained unchanged after stimulation with the different conditioned media. Interestingly, these extreme effects on the functionality, morphology, and expression profile of cortical neurons were only observed for astrocytes and microglia alone, respectively, and were partly compensated in environments in which both were cultivated together.
Additionally, in vivo experiments were performed on control mice and mice receiving different doses of paclitaxel-injections. However, immunohistochemical stainings indicated no neuronal loss, neurogenesis, or microglial activation. On the one hand, this suggested that cognitive impairments are due to functional, and not due to structural changes. On the other hand, the question remains open, which functional changes are induced by paclitaxel and what are the underlying mechanisms in vivo. In this field, further investigations are necessary. Overall, we propose that data from this project reveal glial cells as potential target for therapeutic strategies to mediate neuroprotection and enhance neurorepair under pathophysiological conditions such as chemotherapy. Notwithstanding, this study shows that the communication between glia and neurons is highly complex, but extremely important for maintaining brain function. This crosstalk is severely modulated even after slight pathological changes and requires further intensive inspections for understanding the potential role of glia under pathological conditions such as the chemobrain
UZBEK FAIRY TALES AND THEIR IMPORTANCE IN CHILD EDUCATION
No full text<p><i>Explaining the importance of fairy tales in raising children</i></p>
ANALYSIS OF PHRASES IN THE TRAGEDY "MEDEA"
No full text<p><i>This article, first of all, talks about the tragedy "Medea" by Euripides, and at the same time about the expressions and proverbs that are very important in the work. About 100 phrases and dozens of proverbs will be analyzed.</i></p>
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Мирзаахмедова Нилюфарнинг томоркасида етиштирилаетган мева кучатлари. Saplings of fruit trees produced by farmers Mrs. Nilufar Mirzaahmedova in her backyard.
No full textМирзаахмедова Нилюфарнинг томоркасида етиштирилаетган мева кучатлари. Saplings of fruit trees produced by farmers Mrs. Nilufar Mirzaahmedova in her backyard
O'ZBEKISTON RESPUBLIKASI KIMYO SANOATIDA INNOVATSION FAOLIYATINI SAMARALI RIVOJLANTIRISH
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SANOAT KORXONALARIDA INVESTITSION FAOLIYATNI TASHKILIYIQTISODIY MEXANIZMINI TAKOMILLASHTIRISH
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No full textBakayeva Nilufar Bahriddinovna O‘ZBEKISTON RESPUBLIKASI OLIY TA'LIM ,FAN VA INNOVATSIYALAR VAZIRLIGI OSIYO XALQARO UNIVERSITETI IQTISODIYOT ( Tarmoqlar va sohalar bõyicha) magistri Annotation: this article reflects information on the effective development of innovative activities in the chemical industry of the Republic of Uzbekista
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