Mechanisms of oxidative stress in human aortic aneurysms — association with clinical risk factors for atherosclerosis and disease severity

Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2radical dot−) production in human AAA. Methods and results: AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n = 16) than in risk factor matched controls (n = 16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2radical dot− in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size. Conclusions: Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients

Vimentin association with nuclear grooves in normal MEF 3T3 cells

Vimentin, an intermediate filament protein present in leukocytes, blood vessel endothelial cells, and multiple mesenchymal cells, such as mouse embryonic fibroblasts (MEF 3T3), is crucial for various cellular processes, as well as for maintaining the integrity and durability (stability) of the cell cytoskeleton. Vimentin intermediate filaments (VIFs) adhere tightly to the nucleus and spread to the lamellipodium and tail of the cell, serving as a connector between the nucleus, and the cell’s edges, especially in terms of transferring mechanical signals throughout the cell. How these signals are transmitted exactly remains under investigation. In the presented work, we propose that vimentin is involved in that transition by influencing the shape of the nucleus through the formation of nuclear blebs and grooves, as demonstrated by microscopic observations of healthy MEF (3T3) cells. Grooved, or “coffee beans” nuclei, have, to date, been noticed in several healthy cells; however, these structures are especially frequent in cancer cells—they serve as a significant marker for recognition of multiple cancers. We observed 288 MEF3T3 cells cultured on polyhydroxyoctanoate (PHO), polylactide (PLA), and glass, and we identified grooves, coaligned with vimentin fibers in the nuclei of 47% of cells cultured on PHO, 50% of cells on glass, and 59% of cells growing on PLA. We also observed nuclear blebs and associated their occurrence with the type of substrate used for cell culture. We propose that the higher rate of blebs in the nuclei of cells, cultured on PLA, is related to the microenvironmental features of the substrate, pH in particular

Supplementary information for the article: Snoch, W., Jarek, E., Milivojevic, D., Nikodinovic-Runic, J., & Guzik, M. (2023). Physicochemical studies of novel sugar fatty acid esters based on (R)-3-hydroxylated acids derived from bacterial polyhydroxyalkanoates and their potential environmental impact. Frontiers in Bioengineering and Biotechnology, 11. https://www.frontiersin.org/articles/10.3389/fbioe.2023.1112053

WS acknowledges the support of InterDokMed project no.POWR.03.02.00-00-I013/16.We thank Marzena Noworyta1 forrepeating pH and interfacial tension measurements and conductivitymeasurements.Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1780]The Supplementary Material for this article can be found online at: [https://www.frontiersin.org/articles/10.3389/fbioe.2023.1112053/full#supplementary-material

Insights into in vitro wound closure on two biopolyesters-polylactide and polyhydroxyoctanoate

Two bio-based polymers have been compared in this study, namely: polylactide (PLA) and polyhydroxyoctanoate (PHO). Due to their properties such as biocompatibility, and biointegrity they are considered to be valuable materials for medical purposes, i.e., creating scaffolds or wound dressings. Presented biopolymers were investigated for their impact on cellular migration strategies of mouse embryonic fibroblasts (MEF) 3T3 cell line. Advanced microscopic techniques, including confocal microscopy and immunofluorescent protocols, enabled the thorough analysis of the cell shape and migration. Application of wound healing assay combined with dedicated software allowed us to perform quantitative analysis of wound closure dynamics. The outcome of the experiments demonstrated that the wound closure dynamics for PLA differs from PHO. Single fibroblasts grown on PLA moved 1.5-fold faster, than those migrating on the PHO surface. However, when a layer of cells was considered, the wound closure was by 4.1 h faster for PHO material. The accomplished work confirms the potential of PLA and PHO as excellent candidates for medical applications, due to their properties that propagate cell migration, vitality, and proliferation—essential cell processes in the healing of damaged tissue

Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications

No abstract available

GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus

Background: The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients.<p></p> Methods: Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA).<p></p> Results: Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables.<p></p> Conclusions: Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients

Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics

AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies i

The influence of novel, biocompatible, and bioresorbable poly(3-hydroxyoctanoate) dressings on wound healing in mice

The human body's natural protective barrier, the skin, is exposed daily to minor or major mechanical trauma, which can compromise its integrity. Therefore, the search for new dressing materials that can offer new functionalisation is fully justified. In this work, the development of two new types of dressings based on poly(3-hydroxyoctanoate) (P(3HO)) is presented. One of the groups was supplemented with conjugates of an anti-inflammatory substance (diclofenac) that was covalently linked to oligomers of hydroxycarboxylic acids (Oli-dicP(3HO)). The novel dressings were prepared using the solvent casting/particulate leaching technique. To our knowledge, this is the first paper in which P(3HO)-based dressings were used in mice wound treatment. The results of our research confirm that dressings based on P(3HO) are safe, do not induce an inflammatory response, reduce the expression of pro-inflammatory cytokines, provide adequate wound moisture, support angiogenesis, and, thanks to their hydrophobic characteristics, provide an ideal protective barrier. Newly designed dressings containing Oli-dicP(3HO) can promote tissue regeneration by partially reducing the inflammation at the injury site. To conclude, the presented materials might be potential candidates as excellent dressings for wound treatment

Supplementary data for the article: Radivojevic, J.; Skaro, S.; Senerovic, L.; Vasiljevic, B.; Guzik, M.; Kenny, S. T.; Maslak, V.; Nikodinovic-Runic, J.; O’Connor, K. E. Polyhydroxyalkanoate-Based 3-Hydroxyoctanoic Acid and Its Derivatives as a Platform of Bioactive Compounds. Applied Microbiology and Biotechnology 2016, 100 (1), 161–172. https://doi.org/10.1007/s00253-015-6984-4

Supplementary material for: [https://doi.org/10.1007/s00253-015-6984-4]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2025

Novel bioresorbable tricalcium phosphate/polyhydroxyoctanoate (TCP/PHO) composites as scaffolds for bone tissue engineering applications

Development of new composite materials for bone tissue engineering is a constantly growing field of medicine. Therefore there is a continuous need in creating novel materials that can not only regenerate the defected tissue but also nourish it while the healing process progresses. Here we present a novel type of composite material that fulfils these requirements. The study describes creation of a composite with macroporous bioceramic core that is infiltrated with a thin biopolymer layer. The ceramic component, namely tricalcium phosphate (TCP), due to its mechanistic and bioactive properties may promote new bone creation as shown through the in vitro studies. To the best of our knowledge the coating layer was created for the first time from a representative of bacterially derived medium chain length polyhydroxyalkanoate polymers (mcl-PHA), namely polyhydroxyoctanoate (PHO). This polymer layer not only profoundly changed the stress-strain characteristics of the bioceramic foam but also released (R)-3-hydroxyacids and their dimers/trimers to the investigated environment. In the manuscript we have in depth characterised these materials employing a set of basic procedures, through 3D structure reconstruction and finishing with prolonged in vitro experiments