62 research outputs found

    Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group

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    The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5′-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5′-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing

    The 2022 South America report of The Lancet Countdown on health and climate change: trust the science. Now that we know, we must act

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    The health of South American populations is being severely impacted by increasing climate change-driven environmental changes. Exacerbated by increased social inequities and vulnerability, deforestation, land degradation, and global climate variabilities in sea temperature, can potentially lead to extreme weather and climate events, magnifying the negative effects of climate change on health. Understanding the direct and indirect exposure routes to climate hazards and the effects on health and wellbeing is critical to design successful and effective evidence-based adaptation and mitigation plans and policies. This report is part of the Lancet Countdown's broader efforts to develop expertise and understanding of the links between health and climate change at the regional level. The Lancet Countdown South America (LCSA), a newly launched chapter of the Lancet Countdown, is an independent, multidisciplinary academic collaboration dedicated to tracking the links between public health and climate change in South America (SA). This collaboration brings together 21 academic institutions and UN agencies with 28 researchers representing various disciplines. The data and results provided in this report for the 12 countries of the region,∗ explore in regional detail the results of the 2022 global Lancet Countdown report and provide the evidence to support targeted response strategies for decision-makers. Its findings and conclusions represent the consensus of experts across multiple fields, covering 25 indicators summarised below in four key messages

    Criteria indicators of formation of economic competence of system of the general education

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    This article analyses the technology of determination of level of formation of economic competence of school students taking into account the developed criteria. The research is fulfilled on the basis of the formulated determination of economic competence and its structure (informative; motivational; activity). Each criterion corresponds with certain indicators reflecting degree of formation of separately taken component

    ARGEOS: A New Bioinformatic Tool for Detailed Systematics Search in GEO and ArrayExpress

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    Conduct a reanalysis of transcriptome data for studying intracellular signaling or solving other experimental problems is becoming increasingly popular. Gene expression data are archived as microarray or RNA-seq datasets mainly in two public databases: Gene Expression Omnibus (GEO) and ArrayExpress (AE). These databases were not initially intended to systematically search datasets, making it challenging to conduct a secondary study. Therefore, we have created the ARGEOS service, which has the following advantages that facilitate the search: (1) Users can simultaneously send several requests that are supposed to be used for systematic searches, and it is possible to correct the requests; (2) advanced analysis of information about the dataset is available. The service collects detailed protocols, information on the number of datasets, analyzes the availability of raw data, and provides other reference information. All this contributes to both rapid data analysis with the search for the most relevant datasets and to the systematic search with detailed analysis of the information of the datasets. The efficiency of the service is shown in the example of analyzing transcriptome data of activated (polarized) cells. We have performed a systematic search of studies of cell polarization (when cells are exposed to different immune stimuli). The web interface for ARGEOS is user-friendly and straightforward. It can be used by a person who is not familiar with database searching

    An Electronic Textbook as a Means of Improving the Quality of Student Learning at the University

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    The origin and development of e-learning methods in Russia and other countries is due to steady progress in the field of information and communication technologies and the general informatization of the educational process, the creation of a global environment for the mutual integration of cultures and disciplines, as well as the establishment of continuing open-ended education that underlies post-industrial (information) society. Under the influence of these processes, there is a need for new, more advanced educational practices, which is the reason for the transformation of both the essence of national education and its formal side. Nowadays, a person should possess not only a certain amount of useful information, but also the ability to learn: search and find the necessary information, use various sources to get out of difficult situations, continuously expand the range of one’s own competencies, and constantly develop, keeping up with what is happening around. In the framework of the modern educational paradigm, the student is considered as a subject of knowledge, and not an object of pedagogical influence. In the early to mid2010s, active contribution to this is made by e-learning (electronic learning, e-learning), which must be used in educational institutions of various types and at different levels of the educational vertical. It makes it possible to integrate into the global scientific community, to become subjects of the interaction of cultures, including the exchange of spiritual values. The introduction of e-learning is one of the key tasks in the context of the modernization of national education. The term «electronic learning» is transmitted into Russian in various ways. The most popular options are: “distance learning / education”, “mobile learning”, “virtual learning”. The European Commission interprets “e-learning” as “the use of new multimedia and Internet technologies to improve the quality of education by improving access to resources and services, as well as remote knowledge sharing and collaboration”. In this study, the term “e-learning” will correspond to the phrase “electronic learning”. This is a learning process based on interactive electronic means of storing and providing information: the Internet, corporate networks, and CD-ROMs

    Comparison of PPAR Ligands as Modulators of Resolution of Inflammation, via Their Influence on Cytokines and Oxylipins Release in Astrocytes

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    Neuroinflammation is a key process of many neurodegenerative diseases and other brain disturbances, and astrocytes play an essential role in neuroinflammation. Therefore, the regulation of astrocyte responses for inflammatory stimuli, using small molecules, is a potential therapeutic strategy. We investigated the potency of peroxisome proliferator-activated receptor (PPAR) ligands to modulate the stimulating effect of lipopolysaccharide (LPS) in the primary rat astrocytes on (1) polyunsaturated fatty acid (PUFAs) derivative (oxylipins) synthesis; (2) cytokines TNFα and interleukin-10 (IL-10) release; (3) p38, JNK, ERK mitogen-activated protein kinase (MAPKs) phosphorylation. Astrocytes were exposed to LPS alone or in combination with the PPAR ligands: PPARα (fenofibrate, GW6471); PPARβ (GW501516, GSK0660); PPARγ (rosiglitazone, GW9662). We detected 28 oxylipins with mass spectrometry (UPLC-MS/MS), classified according to their metabolic pathways: cyclooxygenase (COX), cytochrome P450 monooxygenases (CYP), lipoxygenase (LOX) and PUFAs: arachidonic (AA), docosahexaenoic (DHA), eicosapentaenoic (EPA). All tested PPAR ligands decrease COX-derived oxylipins; both PPARβ ligands possessed the strongest effect. The PPARβ agonist, GW501516 is a strong inducer of pro-resolution substances, derivatives of DHA: 4-HDoHE, 11-HDoHE, 17-HDoHE. All tested PPAR ligands decreased the release of the proinflammatory cytokine, TNFα. The PPARβ agonist GW501516 and the PPARγ agonist, rosiglitazone induced the IL-10 release of the anti-inflammatory cytokine, IL-10; the cytokine index, (IL-10/TNFα) was more for GW501516. The PPARβ ligands, GW501516 and GSK0660, are also the strongest inhibitors of LPS-induced phosphorylation of p38, JNK, ERK MAPKs. Overall, our data revealed that the PPARβ ligands are a potential pro-resolution and anti-inflammatory drug for targeting glia-mediated neuroinflammation
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