1. Nano spray-dried particles of in-situ crosslinked alginate and their toxicological characterisationJaka Levanič, Ilja Gasan Osojnik Črnivec, Iza Rozman, Mihaela Skrt, Alja Štern, Bojana Žegura, Nataša Poklar Ulrih, 2024, izvirni znanstveni članek Povzetek: The feasibility and technical capacity for producing crosslinked sub-micron gels with a nano spray-dryer were studied with variable pH systems incorporating alginate, pectin, and pullulan. The obtained powders were characterized for their morphology, particle size distribution, and their toxicological safety profile using genotoxicity and cytotoxicity assays. Additionally, quercetin was added to the encapsulation system to study the potential of the system to encapsulate this material. The produced powders exhibited morphologies and particle size distributions characteristic for nano spray-drying. The addition of pullulan and pectin to the feed solutions resulted in a particle size increase, with crosslinked alginate particles having a mean value of 1.43 μm, while particles with added pectin and pullulan had a mean particle size of 1.70 and 1.75 μm, respectively. The inclusion of quercetin proved to be problematic with this encapsulation system. Extremely high degradation rates and extremely low encapsulation efficiencies were observed due to the alkaline pH (~10) of the system that is needed to keep the feed dispersion in a liquid state and prevent premature crosslinking of the alginate. Although pectin and pullulan provided some protection for quercetin in the alkaline dispersion, the absolute quercetin content in the final product remained very low, with a maximum achieved encapsulation efficiency of 2.06 %. The safety profile of most produced powders was favourable, as they did not exhibit any significant cytotoxic and genotoxic activity in the HepG2 cell line, except in the case of Alginate/Pullulan which showed a 43 % decrease in cell viability at 500 μg/mL. Samples where quercetin was added did not show any increased toxicological effect. Ključne besede: alginate, polysaccharides, crosslinking, nano spray drying, toxicological evaluation Objavljeno v DiRROS: 08.05.2025; Ogledov: 224; Prenosov: 119
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2. Modulation of the proteasome pathway by nano-curcumin and curcumin in retinal pigment epithelial cellsJ. Emanuel Ramos de Carvalho, Milan T. Verwoert, Ilse M.C. Vogels, Sabine Schipper-Krom, Cornelis J. F. van Noorden, Eric A. Reits, Ingeborg Klaassen, Reinier O. Schlingemann, 2018, izvirni znanstveni članek Povzetek: Introduction: Curcumin has multiple biological effects including the modulation of protein homeostasis by the ubiquitin-proteasome system. The purpose of this study was to assess the in vitro cytotoxic and oxidative effects of nano-curcumin and standard curcumin and characterize their effects on proteasome regulation in retinal pigment epithelial (RPE) cells. Methods: Viability, cell cycle progression, and reactive oxygen species (ROS) production were determined after treatment with nano-curcumin or curcumin. Subsequently, the effects of nano-curcumin and curcumin on proteasome activity and the gene and protein expression of proteasome subunits PA28α, α7, β5, and β5i were assessed. Results: Nano-curcumin (5-100 μM) did not show significant cytotoxicity or anti-oxidative effects against H2O2-induced oxidative stress, whereas curcumin (≥10 μM) was cytotoxic and a potent inducer of ROS production. Both nano-curcumin and curcumin induced changes in proteasome-mediated proteolytic activity characterized by increased activity of the proteasome subunits β2 and β5i/β1 and reduced activity of β5/β1i. Likewise, nano-curcumin and curcumin affected mRNA and protein levels of household and immunoproteasome subunits. Conclusions: Nano-curcumin is less toxic to RPE cells and less prone to induce ROS production than curcumin. Both nano-curcumin and curcumin increase proteasome-mediated proteolytic activity. These results suggest that nano-curcumin may be regarded as a proteasome-modulating agent of limited cytotoxicity for RPE cells.
Ključne besede: curcumin, nano-curcumin, proteasome, retinal pigment epithelium Objavljeno v DiRROS: 26.02.2025; Ogledov: 305; Prenosov: 157
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3. Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model : in situ detection of 2-HG and [alpha]-KGAnna C. Navis, Simone P. Niclou, Fred Fack, Daniel Stieber, Sanne A. M. van Lith, Kiek Verrijp, Alan F. Wright, Jonathan Stauber, Bastiaan Tops, Irene Otte-Holler, Ron A. Wevers, Arno van Rooij, Stefan Pusch, Andreas von Deimling, Wikky Tigchelaar, Cornelis J. F. van Noorden, Pieter Wesseling, William P. J. Leenders, 2013, izvirni znanstveni članek Povzetek: Background
Point mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level.
Results
LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis.
Conclusions
The oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations. Ključne besede: gliomaI, IDH mutations, xenograft, D-2-hydroxyglutarate, [alpha]-ketoglutarate, mitochondria: LESA-nano ESI-FTIC Objavljeno v DiRROS: 02.08.2024; Ogledov: 579; Prenosov: 377
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4. Degradation and Stabilization of Polymer MaterialsBranka Mušič, Andrijana Sever Škapin, 2023, drugi znanstveni članki Ključne besede: polymer-based materials, nano, micro, and macro composites, effects on (micro) organisms and toxicity, impact on the ecosystem, mechanisms and products of accelerated aging and degradation, physical, chemical, mechanical, thermal, and morphological, analysis, biodegradability, sustainability, life cycle, renewable and recycled resources and the circular economy Objavljeno v DiRROS: 21.12.2023; Ogledov: 1032; Prenosov: 476
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5. Improved synthetic route of incorporation of nanosilicon species into phenol-formaldehyde resin and preparation of novel ZnAl-layered double-hydroxide hybrid phenol-formaldehyde resinAna Dremelj, Romana Cerc Korošec, Andreja Pondelak, Branka Mušič, 2022, izvirni znanstveni članek Povzetek: Hybrid phenol-formaldehyde (PF) resins represent one of the most important niche groups of binding systems for composites. New industrial needs, environmental requirements, and price fluctuations have led to further research on materials with enhanced mechanical and thermal properties. The preparation of novel hybrid materials can be achieved by inclusion of various elements or functional groups in the organic polymer phenolic framework. Herein, we report the synthesis and characterization of a PF-based hybrid material with different nanoscale silicone species and ZnAl-layered double hydroxide (LDH). The main goals of this study were to improve the synthetic pathways of hybrid resin, as well as to prepare granulated composite materials and test samples and determine their characterization. Added inorganic species increased the glass-transition temperature by a minimum of 8 °C, which was determined using differential scanning calorimetry (DSC). Rheological properties (melting viscosity and flow distance) of the hybrid resin were measured. The homogeneity of distribution of added species across the organic matrix was evaluated with scanning electron microscopy (SEM). With synthesized new hybrid-binding systems, we prepared different granulated composite materials and evaluated them with the measurements of rheological properties (flow curing characteristics). Tensile strength of samples, prepared from granulated composite material, improved by more than 5%. Ključne besede: phenol-formaldehyde hybrid resins, nano-SiO2, ZnAl-LDH, composites, glass-transition temperature, mechanical properties Objavljeno v DiRROS: 03.05.2023; Ogledov: 1018; Prenosov: 557
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