125 research outputs found
Inhibition of zymosan-induced kidney dysfunction by tyrphostin AG-490
No full textBACKGROUND: Zymosan-induced shock has been associated with an increased production of pro-inflammatory cytokines and mediators, causing a generalized dysfunction of liver, lung and kidneys. Herein, we investigate the effects of tyrphostin AG-490 on the early inflammation and on the late renal injury provoked by zymosan injection. METHODS: Shock was induced by intraperitoneal injection of zymosan in a dose of 0.8-1.0 mg/g body weight in BALB/c mice and 0.8 mg/g body weight in SCID mice. Tyrphostin AG-490 was administered intraperitoneally in a dose of 5 mg/kg immediately after shock induction. Blood, peritoneal lavage and kidneys were collected at certain time points after zymosan injection. The levels of MIP-1alpha, RANTES, IL-6, IL-10, alpha1-antitrypsin and C5a in plasma were determined by ELISA. The number of IL-10-secreting cells in peritoneum was assayed by ELISPOT. Kidney function was monitored by measurement of urine/plasma creatinine levels and proteinuria. Histological assessment of renal injury was performed in a blinded fashion after hematoxylin/eosin staining. Immunohistochemistry analyses were used to evaluate the expression of C5aR, STAT1, STAT3 and the binding ability of IgGs in kidneys. RESULTS: Tyrphostin AG-490 attenuated the early phase of zymosan-induced shock via inhibition of MIP-1alpha, RANTES and C5a plasma levels and via elevation of IL-10 in plasma. The drug increased IL-10 production in peritoneum and the number of IL-10-secreting peritoneal cells. AG-490 was able to retain the time of coagulation and the level of alpha1-antitrypsin to normal values. At the late stage of shock, AG-490 decreased scores of tubular injury, cell infiltration and glomerular lesions in parallel with diminished creatinine plasma level and protein excretion. These beneficial effects of AG-490 were related to lowered levels of circulating IL-6, MIP-1alpha and C5a, and to inhibited expression of STAT1, STAT3 and C5aR in kidneys. The drug diminished the production of zymosan-specific IgG antibodies and hindered the glomeruli from IgGs recognition. CONCLUSION: Tyrphostin AG-490 reduced the magnitude of the initial inflammatory response in zymosan-induced shock and prevented the development of severe kidney dysfunction. Our data suggest that the drug might be used as a therapeutic approach in cases where shock is combined with acute renal injury
Targeting the PI3K/AKT/mTOR signaling pathway in medulloblastoma
No full textMedulloblastoma is the most common malignant childhood brain tumor and is associated with a poor outcome. There is an urgent need to develop novel targeted therapeutic approaches for medulloblastoma, which will arise from an enhanced understanding of the disease at the molecular level. Medulloblastoma has been recognized to be a heterogeneous disease, and no recurrent cancer gene mutations have been found, although many of the mutations described so far affect key intracellular signaling pathways, such as sonic hedgehog (SHH) and Wnt/β-catenin. The PI3K/AKT/mTOR (PAM) signaling pathway controls key cellular responses, such as cell growth and proliferation, survival, migration and metabolism. Over the last decades, it has been recognized that this intracellular signaling pathway is frequently activated by genetic and epigenetic alterations in malignant brain tumors, including medulloblastoma. Clinical trials have started to evaluate the safety and efficacy of agents targeting this pathway in malignant brain tumors. Due to the complexity of the PAM signaling pathway, there remain significant difficulties in the development of novel therapeutic approaches. The future challenges in developing effective treatments for cancer patients include the development of predictive biomarkers and combinatorial approaches to effectively target multiple signal transduction pathways. In this review article, we will summarize the current knowledge about the role of PAM signaling in medulloblastoma and discuss the strategies that are currently being evaluated with targeted agents against this pathway
The Phosphoinositide 3-Kinase p110α Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma.
No full textMedulloblastoma (MB) is the most common malignant brain tumor in childhood and represents the main cause of cancer-related death in this age group. The phosphoinositide 3-kinase (PI3K) pathway has been shown to play an important role in the regulation of medulloblastoma cell survival and proliferation, but the molecular mechanisms and downstream effectors underlying PI3K signaling still remain elusive. The impact of RNA interference (RNAi)-mediated silencing of PI3K isoforms p110α and p110δ on global gene expression was investigated by DNA microarray analysis in medulloblastoma cell lines. A subset of genes with selectively altered expression upon p110α silencing in comparison to silencing of the closely related p110δ isoform was revealed. Among these genes, the leukemia inhibitory factor receptor α (LIFR α) was validated as a novel p110α target in medulloblastoma. A network involving c-Myc and miR-125b was shown to be involved in the control of LIFRα expression downstream of p110α. Targeting the LIFRα by RNAi, or by using neutralizing reagents impaired medulloblastoma cell proliferation in vitro and induced a tumor volume reduction in vivo. An analysis of primary tumors revealed that LIFRα and p110α expression were elevated in the sonic hedgehog (SHH) subgroup of medulloblastoma, indicating its clinical relevance. Together, these data reveal a novel molecular signaling network, in which PI3K isoform p110α controls the expression of LIFRα via c-Myc and miR-125b to promote MB cell proliferation
Russia's self-presentation on Evening with Vladimir Solovyov on the example of the Kherson retreat
No full textThis bachelor thesis examines the way Russia presents itself in the propagandistic TV show Evening with Vladimir Solovyov. The research is set against the backdrop of the retreat of Russian troops from Kherson, which took place in November 2022 and was a significant event within the context of the Russian war against Ukraine. The core of the thesis investigates how Russia is portrayed by the show's guests and how the principle of contrasts is utilized, defining Russia indirectly by contrasting it with the West. Firstly, the thesis introduces the concept of propaganda, providing a closer explanation of the term, and focuses specifically on Russian propaganda to clarify the analytical framework. Subsequently, the context of the war in Ukraine is presented, contextualizing the retreat of Russian troops from Kherson. Four episodes of the show, which were recorded and broadcasted immediately before, during, and after the retreat from Kherson, are then analyzed. The author examines how Russia is presented in these episodes and how definitions of the West are used in its portrayal. Statements by the propagandists describing the West are identified, indirectly characterizing Russia as well. Then, specific definitions are compared with their opposites through post-structuralist analysis. Finally, the thesis..
English language courses for librarians (ESP), 2018, 23-25 august, Minsk, Belarus [Articol]
No full textThe author describes the participation of Balti librarians in the English Language Courses for Librarians (ESP) organized at the Fundamental Library of the Belorusian State University in Minsk in the framework of the Erasmus + Program, “,,Library Network Support Services: modernising libraries in Armenia, Moldova and Belarus through library staff development and reforming libraries [LNSS],” The training was promoted by Professor Gerard Cullen and trainer Valeriya Racheeva, the representatives of the project, The Pyramid Group, in Germany
Виртуальность как атрибут пространства и времени современного социума
No full textThe paper is devoted to a characterization of a social time and social space of the moder informational civilization. The author considers new values, characterizations of society, communicative practices and relationships arising due to social existence in a virtual space and virtual time.Стаття присвячена характеристицi соцiального часу i соцiального простoру сучасної iнформацiйної цивiлiзацiї. Автор розглядає новi цiнностi, характеристики суспiльства, комунiкативнi практики i вiдносини, що виникли внаслiдок iснування суспiльства у вiртуальному просторi i вiртуальному часi
Involvement of soluble receptor activator of nuclear factor-κB ligand (sRANKL) in collagenase-induced murine osteoarthritis and human osteoarthritis
No full textInternational audienceJoint destruction and excessive bone formation are associated with high expression of soluble receptor activator of nuclear factor-κB ligand (sRANKL). This study was undertaken to investigate the role of sRANKL in collagenase-induced osteoarthritis (CIOA) in mice and in patients with osteoarthritis (OA). The initial phase of CIOA was associated with severe proteoglycan depletion, decreased collagen density, and up-regulation of bone morphogenetic protein (BMP)-2. At the late stage of CIOA, bone remodeling was related with increased BMP2 and RANKL expression in the joints, high sRANKL, and decreased number of activated neutrophils in synovium. CIOA mice showed elevated plasma level of sRANKL but low RANKL expression on blood neutrophils. The percentage of RANKL-positive blood neutrophils was higher in patients with OA than in healthy individuals. Our data indicate that increased local and systemic levels of soluble RANKL might be indicative for OA disorders in mouse and human
RESEARCH ON THE FORMATION OF INVARIANT AND PROFESSIONALLY IMPORTANT QUALITIES OF FUTURE EDUCATORS-PSYCHOLOGISTS
No full textIn the report the author reveals the concept of professionally important invariant qualities of an educator-psychologist. The author offers the results of the experimental research, which allowed to discover professionally important invariant qualities of an educator-psychologist at the stage of professional training
RNA interference screening identifies a novel role for PCTK1/CDK16 in medulloblastoma with c-Myc amplification.
No full textMedulloblastoma (MB) is the most common malignant brain tumor in children and is associated with a poor outcome. cMYC amplification characterizes a subgroup of MB with very poor prognosis. However, there exist so far no targeted therapies for the subgroup of MB with cMYC amplification. Here we used kinome-wide RNA interference screening to identify novel kinases that may be targeted to inhibit the proliferation of c-Myc-overexpressing MB. The RNAi screen identified a set of 5 genes that could be targeted to selectively impair the proliferation of c-Myc-overexpressing MB cell lines: AKAP12 (A-kinase anchor protein), CSNK1α1 (casein kinase 1, alpha 1), EPHA7 (EPH receptor A7) and PCTK1 (PCTAIRE protein kinase 1). When using RNAi and a pharmacological inhibitor selective for PCTK1, we could show that this kinase plays a crucial role in the proliferation of MB cell lines and the activation of the mammalian target of rapamycin (mTOR) pathway. In addition, pharmacological PCTK1 inhibition reduced the expression levels of c-Myc. Finally, targeting PCTK1 selectively impaired the tumor growth of c-Myc-overexpressing MB cells in vivo. Together our data uncover a novel and crucial role for PCTK1 in the proliferation and survival of MB characterized by cMYC amplification
Russia's self-presentation on Evening with Vladimir Solovyov on the example of the Kherson retreat
No full textBakalářská práce se věnuje způsobu sebeprezentace Ruska v propagandistickém televizním pořadu Večer s Vladimirem Solovjovem. Výzkum je zasazen do období ústupu ruských vojsk z Chersonu, který proběhl v listopadu 2022 a který byl v rámci ruské války proti Ukrajině významnou událostí. V jádru práce je zkoumáno, jak je v pořadu Rusko přítomnými hosty prezentováno a jak je k tomu využíván princip protikladů, tedy nepřímého definování Ruska na základě definování jeho opaku - v tomto případě Západu. Práce nejprve představuje pojem propaganda, který blíže vysvětluje, a také se zaměřuje konkrétně na propagandu ruskou, aby bylo zřetelnější, s čím je v samotné analýze pracováno. Následně je představen kontext války na Ukrajině, čímž práce dává do souvislosti ústup ruských vojsk z Chersonu. Následně jsou analyzovány čtyři díly pořadu, které byly natáčeny a vysílány bezprostředně před, v průběhu a po ústupu z Chersonu. Autorka v těchto dílech zkoumá, jak je v nich Rusko prezentováno a jak jsou k jeho prezentaci využívány definice Západu. Identifikuje v nich výroky přítomných propagandistů, které zřetelně popisují Západ a zároveň nepřímo také Rusko samotné. Následně už jsou konkrétní definice syntézou porovnány s jejich protiklady, a to za pomoci poststrukturalistické analýzy. Práce v závěru zodpovídá výzkumnou...This bachelor thesis examines the way Russia presents itself in the propagandistic TV show Evening with Vladimir Solovyov. The research is set against the backdrop of the retreat of Russian troops from Kherson, which took place in November 2022 and was a significant event within the context of the Russian war against Ukraine. The core of the thesis investigates how Russia is portrayed by the show's guests and how the principle of contrasts is utilized, defining Russia indirectly by contrasting it with the West. Firstly, the thesis introduces the concept of propaganda, providing a closer explanation of the term, and focuses specifically on Russian propaganda to clarify the analytical framework. Subsequently, the context of the war in Ukraine is presented, contextualizing the retreat of Russian troops from Kherson. Four episodes of the show, which were recorded and broadcasted immediately before, during, and after the retreat from Kherson, are then analyzed. The author examines how Russia is presented in these episodes and how definitions of the West are used in its portrayal. Statements by the propagandists describing the West are identified, indirectly characterizing Russia as well. Then, specific definitions are compared with their opposites through post-structuralist analysis. Finally, the thesis...Department of Russian and East European StudiesKatedra ruských a východoevropských studiíFakulta sociálních vědFaculty of Social Science
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