Efekt interference v lipidové signální cestě na cytotoxicitu sorafenibu a funkci efluxních transportérů u buněk myšího hepatocelulárního karcinomu

Univerzita Karlova Farmaceutická fakulta v Hradci Králové Katedra farmakologie a toxikologie Studentka: Aigul Sagandykova Školitel: PharmDr. Martina Čečková Ph.D. Konzultant: Dr. Mikko Gynther Ph.D. Název diplomové práce: Efekt interference v lipidové signální cestě na cytotoxicitu sorafenibu a funkci efluxních transportérů u buněk myšího hepatocelulárního karcinomu. Nádorová onemocnění představují i v současné době jednu z celosvětově nejvýznamnějších terapeutických výzev. Chemoterapie dosud zůstává základním přístupem v léčbě maligních onemocnění. Její léčebné výsledky nicméně komplikuje mnohočetná léková rezistence (MDR), fenomén popsaný jako ztráta citlivosti nádorových buněk vůči širokému spektru chemoterapeutických léčiv. Dobře známou příčinou MDR je zvýšení exprese a/nebo zvýšení aktivity efluxních lékových transportérů ATP-dependentní transportérové rodiny (tzv. ABC transportérů), jež byly nalezeny v mnoha typech nádorů. V posledním desetiletí stále větší množství vědecké literatury věnuje pozornost novému znaku nádorových buněk - zánětu. Zánětlivé mikroprostředí potencuje tumorigenezi a up regulaci transportérů. Navíc řada pozorování potvrzuje, že ABC transportéry zprostředkovávají přenos signálních lipidů. Tento nový pohled vede k možnosti volby protizánětlivé léčby jako nového přístupu v...Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Aigul Sagandykova Supervisor: PharmDr. Martina Čečková, Ph.D. Consultant: Dr. Mikko Gynther Ph.D. Title of diploma thesis: The effect of lipid signalling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells. Nowadays cancer remains one of the most challenging health issues worldwide. Chemotherapy represents one of the essential approaches in the treatment of malignant diseases. However, multidrug resistance (MDR), a multifactorial phenomenon described as a loss of sensitivity of cancer cells to several diverse chemotherapeutic agents at the same time, often compromises the therapy outcomes. A well-known cause of MDR is an increased expression or/and an enhanced activity of efflux drug transporters of ATP binding cassette (ABC) superfamily, which has been found in many types of cancer. In the last decade, an expanding body of literature suggested a new hallmark of cancer cells - inflammation. An inflammatory microenvironment potentiates tumorigenesis and upregulation of transporters. Moreover, several observations show that ABC transporters mediate the transport of some signalling lipids. This new insight provided...Katedra farmakologie a toxikologieDepartment of Pharmacology and ToxicologyFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov

The effect of lipid signaling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Aigul Sagandykova Supervisor: PharmDr. Martina Čečková, Ph.D. Consultant: Dr. Mikko Gynther Ph.D. Title of diploma thesis: The effect of lipid signalling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells. Nowadays cancer remains one of the most challenging health issues worldwide. Chemotherapy represents one of the essential approaches in the treatment of malignant diseases. However, multidrug resistance (MDR), a multifactorial phenomenon described as a loss of sensitivity of cancer cells to several diverse chemotherapeutic agents at the same time, often compromises the therapy outcomes. A well-known cause of MDR is an increased expression or/and an enhanced activity of efflux drug transporters of ATP binding cassette (ABC) superfamily, which has been found in many types of cancer. In the last decade, an expanding body of literature suggested a new hallmark of cancer cells - inflammation. An inflammatory microenvironment potentiates tumorigenesis and upregulation of transporters. Moreover, several observations show that ABC transporters mediate the transport of some signalling lipids. This new insight provided..

Exploring Kazakhstani General Education Teachers’ Attitudes towards Inclusive Education

Classroom teachers play a crucial role in educational process therefore their positive attitude towards inclusive education is the main key point in its successful implementation. The purpose of this research is to investigate general education teachers’ attitudes towards the inclusion of children with special educational needs in mainstream schools in the northern part of Kazakhstan. The study addresses two research questions: what teachers’ general attitudes towards inclusive education are and what teacher-related variables are associated with teachers’ attitudes towards inclusion. Mixed research methods were employed for the study. The quantitative data was collected via online survey with the use of the Sentiments, Attitudes and Concerns about Inclusive Education Revised (SACIE-R) Scale (Forlin, Earle, Loreman and Sharma, 2011). The qualitative data was collected in the form of one-on-one semi-structured interviews that provided detailed and context-specific data. The research revealed that overall, general education teachers’ attitudes towards inclusive education in the northern part of Kazakhstan are neutral. It means that teachers do not express a strong desire or reluctance to work with children with special educational needs. Teachers’ gender does not influence their attitudes as research showed, however their experience working with students with disabilities do play an essential role in the work making teachers more confident and promoting more positive attitudes towards inclusion. The research findings highlight the need for more in-service trainings for general education teachers. This research is relevant for university students, teachers, and scholars exploring the same topic of teachers’ attitudes towards inclusive education. The results might be beneficial for future policy guidance and useful to develop some particular strategies which can promote positive attitudes among teachers...

The effect of lipid signaling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Aigul Sagandykova Supervisor: PharmDr. Martina Čečková, Ph.D. Consultant: Dr. Mikko Gynther Ph.D. Title of diploma thesis: The effect of lipid signalling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells. Nowadays cancer remains one of the most challenging health issues worldwide. Chemotherapy represents one of the essential approaches in the treatment of malignant diseases. However, multidrug resistance (MDR), a multifactorial phenomenon described as a loss of sensitivity of cancer cells to several diverse chemotherapeutic agents at the same time, often compromises the therapy outcomes. A well-known cause of MDR is an increased expression or/and an enhanced activity of efflux drug transporters of ATP binding cassette (ABC) superfamily, which has been found in many types of cancer. In the last decade, an expanding body of literature suggested a new hallmark of cancer cells - inflammation. An inflammatory microenvironment potentiates tumorigenesis and upregulation of transporters. Moreover, several observations show that ABC transporters mediate the transport of some signalling lipids. This new insight provided..

KAZAKHSTANI AND FOREIGN EXPERIENCE OF UNIVERSITY DIGITALIZATION

The article is devoted to Kazakhstani and foreign experiences in the field of digital transformation of universities. The transitional experiences of domestic and universities abroad, the appropriate research published in open sources, the advanced university’s policy and original studies led to the categorization of digitalization experiences of the world universities in online support, in personalization and interaction along with the missing components of digitalization at Kazakhstani universities. Comparative analysis of IITU’s experience of digitalization and the world technical universities, in particular the Heriot-Watt University, the high ranked Scottish and British higher school as the best universities in the world allow to sum up the ways of transformation of the Kazakhstan University. According to Independent Distance Learning Resources Policy, the general elements and their functions were classified. A number of web-based applications available to perform key tasks such as remote e-mail access, use of a virtual learning environment, online tuition and residency fees were presented.Мақала университеттердің цифрлық трансформациясы саласындағы қазақстандық және шетелдік тәжірибеге арналған. Отандық және шетелдік университеттердің өтпелі тәжірибесі, ашық дереккөздерде жарияланған тиісті зерттеулер, озық университеттік саясат және түпнұсқа зерттеулер әлемдік университеттердің цифрландыру тәжірибесін онлайн-қолдау, дербестендіру және қазақстандық жоғары оқу орындарында цифрландырудың жетіспейтін құрамдас бөліктерімен өзара әрекеттесу бойынша санаттарға бөлуге әкелді. ХАТУ-дың және әлемдік техникалық жоғары оқу орындарының, атап айтқанда, әлемнің үздік университеттері саналатын шотланд және британ жоғары мектебі деп танылған Хериот-Ватт университетінің цифрландыру тәжірибесін салыстырмалы талдау қазақстандық университетті трансформациялау жолын қорытындылауға мүмкіндік береді. Қашықтықтан оқыту ресурстарының тәуелсіз саясатына сәйкес жалпы элементтер мен олардың функциялары жіктелді. Электрондық поштаға қашықтан қол жеткізу, виртуалды оқу ортасын пайдалану, онлайн оқыту және тұру ақысы сияқты негізгі тапсырмаларды орындау үшін қол жетімді бірқатар веб-қосымшалар енгізілді.. Статья посвящена казахстанскому и зарубежному опыту в области цифровой трансформации вузов. Переходный опыт отечественных и зарубежных университетов, соответствующие исследования, опубликованные в открытых источниках, передовая университетская политика и оригинальные исследования привели к категоризации опыта цифровизации мировых университетов в онлайн-поддержке, в персонализации и взаимодействии с недостающими компонентами цифровизации в казахстанских вузах. Сравнительный анализ опыта цифровизации МУИТ и мировых технических вузов, в частности Университета Хериота-Ватта, признанной шотландской и британской высшей школой лучших университетов мира, позволяют подвести итоги путей трансформации казахстанского университета. Были классифицированы общие элементы и их функции в соответствии с Независимой политикой ресурсов дистанционного обучения. Представлен ряд веб-приложений, доступных для выполнения ключевых задач, таких как удаленный доступ к электронной почте, использование виртуальной среды обучения, онлайн-обучение и плата за проживание

Interactions of Whey Proteins with Metal Ions

Whey proteins tend to interact with metal ions, which have implications in different fields related to human life quality. There are two impacts of such interactions: they can provide opportunities for applications in food and nutraceuticals, but may lead to analytical challenges related to their study and outcomes for food processing, storage, and food interactions. Moreover, interactions of whey proteins with metal ions are complicated, requiring deep understanding, leading to consequences, such as metalloproteins, metallocomplexes, nanoparticles, or aggregates, creating a biologically active system. To understand the phenomena of metal–protein interactions, it is important to develop analytical approaches combined with studies of changes in the biological activity and to analyze the impact of such interactions on different fields. The aim of this review was to discuss chemistry of β-lactoglobulin, α-lactalbumin, and lactotransferrin, their interactions with different metal ions, analytical techniques used to study them and the implications for food and nutraceuticals

New Methodology for the Identification of Metabolites of Saccharides and Cyclitols by Off-Line EC-MALDI-TOF-MS

A combination of electrochemistry (EC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (off-line EC-MALDI-TOF-MS) was applied for determination of the studied biologically active compounds (D-glucose, D-fructose, D-galactose, D-pinitol, L-chiro-inositol, and myo-inositol) and their possible electrochemical metabolites. In this work, boron-doped diamond electrode (BDD) was used as a working electrode. MALDI-TOF-MS experiments were carried out (both in positive and negative ion modes and using two matrices) to identify the structures of electrochemical products. This was one of the first applications of the EC system for the generation of electrochemical products produced from saccharides and cyclitols. Moreover, exploratory data analysis approaches (correlation networks, hierarchical cluster analysis, weighted plots) were used in order to present differences/similarities between the obtained spectra, regarding the class of analyzed compounds, ionization modes, and used matrices. This work presents the investigation and comparison of fragmentation patterns of sugars, cyclitols, and their respective products generated through the electrochemistry (EC) process

Metabolic profiling of bacteria with the application of polypyrrole-MOF SPME fibers and plasmonic nanostructured LDI-MS substrates

Abstract Here we present application of innovative lab-made analytical devices such as plasmonic silver nanostructured substrates and polypyrrole-MOF solid-phase microextraction fibers for metabolic profiling of bacteria. For the first time, comprehensive metabolic profiling of both volatile and non-volatile low-molecular weight compounds in eight bacterial strains was carried out with utilization of lab-made devices. Profiles of low molecular weight metabolites were analyzed for similarities and differences using principal component analysis, hierarchical cluster analysis and random forest algorithm. The results showed clear differentiation between Gram positive (G+) and Gram negative (G−) species which were identified as distinct clusters according to their volatile metabolites. In case of non-volatile metabolites, differentiation between G+ and G− species and clustering for all eight species were observed for the chloroform fraction of the Bligh & Dyer extract, while methanolic fraction failed to recover specific ions in the profile. Furthermore, the results showed correlation between volatile and non-volatile metabolites, which suggests that lab-made devices presented in the current study might be complementary and therefore, useful for species differentiation and gaining insights into bacterial metabolic pathways

Mechanistic chromatographic column characterization for the analysis of flavonoids using quantitative structure?retention relationships based on density functional theory

10.3390/ijms21062053International Journal of Molecular Sciences216205

Silver Nanostructured Substrates in LDI-MS of Low Molecular Weight Compounds

Mass spectrometric techniques can provide data on the composition of a studied sample, utilizing both targeted and untargeted approaches to solve various research problems. Analysis of compounds in the low mass range has practical implications in many areas of research and industry. Laser desorption ionization techniques are utilized for the analysis of molecules in a low mass region using low sample volume, providing high sensitivity with low chemical background. The fabrication of substrates based on nanostructures to assist ionization with well-controlled morphology may improve LDI-MS efficiency for silver nanoparticles with plasmonic properties. In this work, we report an approach for the preparation of silver nanostructured substrates applied as laser desorption ionization (LDI) plates, using the chemical vapor deposition (CVD) technique. Depending on the mass of used CVD precursor, the approach allowed the synthesis of LDI plates with tunable sensitivity for various low molecular weight compounds in both ion-positive and ion-negative modes. Reduced chemical background and sensitivity to small biomolecules of various classes (fatty acids, amino acids and water-soluble metabolites) at nanomolar and picomolar detection levels for lipids such as triacylglycerols, phosphatidylethanolamines and lyso-phosphatidylcholines represent an emerging perspective for applications of LDI-MS plates for the collection of molecular profiles and targeted analysis of low molecular weight compounds for various purposes