Steatosis-induced proteins adducts with lipid peroxidation products and nuclear electrophilic stress in hepatocytes

AbstractAccumulating evidence suggests that fatty livers are particularly more susceptible to several pathological conditions, including hepatic inflammation, cirrhosis and liver cancer. However the exact mechanism of such susceptibility is still largely obscure. The current study aimed to elucidate the effect of hepatocytes lipid accumulation on the nuclear electrophilic stress. Accumulation of intracellular lipids was significantly increased in HepG2 cells incubated with fatty acid (FA) complex (1mM, 2:1 oleic and palmitic acids). In FA-treated cells, lipid droplets were localized around the nucleus and seemed to induce mechanical force, leading to the disruption of the nucleus morphology. Level of reactive oxygen species (ROS) was significantly increased in FA-loaded cells and was further augmented by treatment with moderate stressor (CoCl2). Increased ROS resulted in formation of reactive carbonyls (aldehydes and ketones, derived from lipid peroxidation) with a strong perinuclear accumulation. Mass-spectroscopy analysis indicated that lipid accumulation per-se can results in modification of nuclear protein by reactive lipid peroxidation products (oxoLPP). 235 Modified proteins involved in transcription regulation, splicing, protein synthesis and degradation, DNA repair and lipid metabolism were identified uniquely in FA-treated cells. These findings suggest that steatosis can affect nuclear redox state, and induce modifications of nuclear proteins by reactive oxoLPP accumulated in the perinuclear space upon FA-treatment

Computational solutions in redox lipidomics – Current strategies and future perspectives

Abstract The high chemical diversity of lipids allows them to perform multiple biological functions ranging from serving as structural building blocks of biological membranes to regulation of metabolism and signal transduction. In addition to the native lipidome, lipid species derived from enzymatic and non-enzymatic modifications (the epilipidome) make the overall picture even more complex, as their functions are still largely unknown. Oxidized lipids represent the fraction of epilipidome which has attracted high scientific attention due to their apparent involvement in the onset and development of numerous human disorders. Development of high-throughput analytical methods such as liquid chromatography coupled on-line to mass spectrometry provides the possibility to address epilipidome diversity in complex biological samples. However, the main bottleneck of redox lipidomics, the branch of lipidomics dealing with the characterization of oxidized lipids, remains the lack of optimal computational tools for robust, accurate and specific identification of already discovered and yet unknown modified lipids. Here we discuss the main principles of high-throughput identification of lipids and their modified forms and review the main software tools currently available in redox lipidomics. Different levels of confidence for software assisted identification of redox lipidome are defined and necessary steps toward optimal computational solutions are proposed

A Single Dose of Atorvastatin Applied Acutely after Spinal Cord Injury Suppresses Inflammation, Apoptosis, and Promotes Axon Outgrowth, Which Might Be Essential for Favorable Functional Outcome.

The aim of our study was to limit the inflammatory response after a spinal cord injury (SCI) using Atorvastatin (ATR), a potent inhibitor of cholesterol biosynthesis. Adult Wistar rats were divided into five experimental groups: one control group, two Th9 compression (40 g/15 min) groups, and two Th9 compression + ATR (5 mg/kg, i.p.) groups. The animals survived one day and six weeks. ATR applied in a single dose immediately post-SCI strongly reduced IL-1β release at 4 and 24 h and considerably reduced the activation of resident cells at one day post-injury. Acute ATR treatment effectively prevented the excessive infiltration of destructive M1 macrophages cranially, at the lesion site, and caudally (by 66%, 62%, and 52%, respectively) one day post-injury, whereas the infiltration of beneficial M2 macrophages was less affected (by 27%, 41%, and 16%). In addition, at the same time point, ATR visibly decreased caspase-3 cleavage in neurons, astrocytes, and oligodendrocytes. Six weeks post-SCI, ATR increased the expression of neurofilaments in the dorsolateral columns and Gap43-positive fibers in the lateral columns around the epicenter, and from day 30 to 42, significantly improved the motor activity of the hindlimbs. We suggest that early modulation of the inflammatory response via effects on the M1/M2 macrophages and the inhibition of caspase-3 expression could be crucial for the functional outcome

Theranostic materials for MRI and targeted delivery based on functionalized magnetite nanoparticles

In the last decades, the synthesis of magnetic nanoparticles, in particular magnetite nanoparticles (MNPs), has received increased attention due to their wide range of applications in biomedicine and technology. MNPs can be effectively used for diagnostics and treatment of various diseases. Size, shape, charge and surface chemistry of NPs are fundamental characteristics that determine substantially their properties. Moreover, these characteristics have a big role in the processes of pharmacokinetics and pharmacodynamics. Magnetite nanoparticles are nontoxic, biocompatible and degradable material. Considering current demographic trends in the world and the nature of the dynamics of morbidity, we can expect that even if the average level of cancer incidence will occur more than 15 million new cases of malignant neoplasms in the population each year. It is obviously that the increase of cancer incidence will be occur substantially due to prostate cancer in men, tumors of the colon and rectum in men and women. Thus the problem of creating universal drug (theranostic materials) for early diagnosis and treatment of malignancy becomes more and more actual. The opportunity of application of magnetite nanoparticles in MRI and drug delivery is highly dependent on their sizes and magnetic characteristics. In this work we attempted to create materials based on MNPs for prostate cancer therapy and diagnostics. We carried out synthesis of magnetite nanoparticles with different morphology (cubes, rod-like, star-like and flower-like) and with average size from 10 to 50 nm. Obtained nanoparticles were synthesized by thermal decomposition of iron-containing precursors in high-boiling organic solvents, as well as the aging method in aqueous medium. All nanoparticles were characterized by different physicochemical methods such as: transmission electron microscopy, X-ray diffraction, thermogravimetric analysis, ICP - MS. Also magnetic measurements of samples were carried out. For transfer of MNPs from the organic into the aqueous medium and to prevent aggregation MNPs were functionalized and coated with biocompatible copolymers based on polyethyleneglycol and pluronic. Please click Additional Files below to see the full abstract

Evaluation of rate of pathological changes in parenchymal organs for embryo of caspian seal <i>Phoca caspica</i> in modern conditions of the ecosystem in the Caspian Sea

Pathological changes of the caspian seal fetus caused by negative processes in the mother’s organism under influence of disease and harmful environments are investigated. For that, parenchymal organs of the fetus are examined by histological methods. Active replacement of the fetus’ tissues by conjunctive tissue is detected in all organs, the most profound abnormalities are registered in the kidney and live

Forms of International Cooperation in Environmental Education: the Experience of Saint Petersburg State University

The authors analyse different forms of environmental education projects and programmes implemented in the Baltic Sea region. The first one is "The Baltic University" programme taught in English. The "Baltic University" is a network of more than 200 universities from 14 counties of the Baltic Sea region. This education programme offers an opportunity for students to enroll on bachelor and master degree programmes related to environmental and social problems of the Baltic Sea region. The Polar and Marine Sciences, POMOR master programme, represents the second form of international environmental education. Russian and German researchers from six universities and four research centres have developed the programme. The target group of the programme are Russian and international students, studying together during the whole duration of the programme. It is the first internationally accredited MA programme taught in English. International accreditation proves the compliance of the programme with international education standards. The same cooperation model is used in a new international master programme - Cold Regions Environmental Landscapes Integrated Science (CORELIS). The programme started in 2016. It is implemented jointly by Hamburg university (the lead partner of the project), and university professors from Helsinki (Finland) and Lisbon (Portugal). Researchers from the Austrian National Institute of Polar Research (Austria, and Lund University (Sweden) will join the programme at a later stage. Such an approach will help achieve the synergy of the European and Russian approaches to environmental education. The Russian-Norwegian master programme "Geoecological monitoring and rational use of natural resources in the Northern oil and gas production regions" is a good example of the third form of international environmental education. The programme similar to POMOR and CORELIS. However, it has one distinctive feature - Russian and foreign students study together from the second term only. The authors describe the ways of achieving the learning objectives of these master programmes depending on the students' language skills and their basic knowledge of ecology and nature management

Akhania, a new genus for Salsola daghestanica, Caroxylon canescens and C. carpathum (Salsoloideae, Chenopodiaceae, Amaranthaceae)

Genus Salsola s.l. was recently split into several genera of different phylogenetic placements within Salsoloideae, but both taxonomic and phylogenetic relationships of some parts of the former broadly defined Salsola still need to be clarified. A remarkable example is Salsola canescens nom. illegit. ≡ Salsola boissieri, a taxon with tricky taxonomic history that was only recently transferred to the genus Caroxylon (tribe Caroxyleae). Salsola daghestanica, a narrow endemic of Central Dagestan (Russian Federation), was not even included in previous molecular studies of Salsoloideae and therefore still lacks an appropriate estimation of its relationships. Molecular phylogeny constructed here using nuclear and plastid DNA sequence data clearly placed Salsola daghestanica and Caroxylon carpathum as sister taxa and the clade S. daghestanica, Caroxylon canescens (Salsola boissieri), C. carpathum (Salsola carpatha) as a sister of the monophyletic Caroxylon. All three species are distinct from Caroxylon from a morphological standpoint. In conclusion, a new genus, Akhania, was established for these taxa. The detailed distribution of Akhania daghestanica is presented for the first time

BioPAN: a web-based tool to explore mammalian lipidome metabolic pathways on LIPID MAPS.

Lipidomics increasingly describes the quantification using mass spectrometry of all lipids present in a biological sample.  As the power of lipidomics protocols increase, thousands of lipid molecular species from multiple categories can now be profiled in a single experiment.  Observed changes due to biological differences often encompass large numbers of structurally-related lipids, with these being regulated by enzymes from well-known metabolic pathways.  As lipidomics datasets increase in complexity, the interpretation of their results becomes more challenging.  BioPAN addresses this by enabling the researcher to visualise quantitative lipidomics data in the context of known biosynthetic pathways.  BioPAN provides a list of genes, which could be involved in the activation or suppression of enzymes catalysing lipid metabolism in mammalian tissues