Phospholipid Cyclosporine Prodrugs Targeted at Inflammatory Bowel Disease (IBD) Treatment: Design,Synthesis, and in Vitro Validation

Novel phospholipid (PL)-cyclosporine conjugates were prepared and studied as potential prodrugs for inflammatory bowel disease (IBD). Our approach relies on phospholipase A₂ (PLA₂), which is overexpressed in the inflamed intestinal tissues, as the prodrug activator to potentially release cyclosporine at the site of inflammation. PL-cyclosporine prodrug conjugates with methylene linkers of various lengths between the sn-2 position of the PL and cyclosporine were synthesized and evaluated for in vitro activation. Surprisingly, despite previous work indicating that conjugates with six methylene linkers between the lipid and drug would suffer rapid enzymatic hydrolysis, with cyclosporine this was not observed. However, compounds with longer linkers (n=10, 12 methylene units) display complete release of the drug by PLA₂-catalyzed hydrolysis, thus demonstrating the importance and profound impact of structural fine-tuning. This study represents a proof-of-concept for our hypothesis and a first step towards a truly targeted IBD treatment with cyclosporine that could be administered throughout the GI tract.     

Inulin-based emulsion-filled gel as a fat replacer in prebiotic- and PUFA-enriched dry fermented sausages

In order to produce fermented sausages with prebiotic fibre and improved fatty acid composition, 16% of pork back fat was replaced with inulin gelled suspension (I) and inulin linseed oil gelled emulsion (IO). Physico-chemical analysis, fatty acid profiles, lipid oxidation, microbiological, textural, colour and sensory analysis were carried out. The fat content was lower in I (31.38%) and IO (35.36%) modified sausages compared to control (44.37%) (P < 0.05). IO sausages had lower SFA and MUFA and higher PUFA content with an improved n-6/n-3 ratio (2.23) (P < 0.05) and α-linolenic acid increment (5.74 g per 100 g). Reformulation led to decrease in springiness, chewiness and hardness and increase in adhesiveness of the sausages. Modified sausages had lower L* and higher a* values, while b* values of I sausages did not differ compared to control sausages. Modified sausages were acceptable regarding all sensory attributes. Lipid oxidation parameters showed higher susceptibility to oxidation and lipolysis in IO sausages.     

Development of protease nanobiocatalysts and their application in hydrolysis of sunflower meal protein isolate

In this study, the suitability of fumed silica nanoparticles (FNS) and its derivatives (amino-modified FNS (AFNS), cyanuric chloride-activated AFNS (CCAFNS) and epoxy-modified FNS (GFNS)), for covalent immobilisation of two commercial protease preparations Alcalase^® and Flavourzyme^® was investigated. The highest hydrolytic activities of immobilised preparations were 25 IU g⁻¹ support (Alcalase-GFNS) and 2.95 IU g⁻¹ support (Flavourzyme-CCAFNS). Furthermore, the immobilised preparations showed 43% and 20% of initial specific activities of commercial protease preparations, respectively. Flavourzyme-CCAFNS also exhibited the highest exopeptidase activity of 22.83 L-pNAU g⁻¹ support. Finally, these two nanobiocatalysts were successfully applied for hydrolysis of sunflower meal protein isolate (SMPI), providing two times higher hydrolysis yields in comparison to free enzymes, justifying the applied immobilisation process. Namely, the highest hydrolysis yield (30%) was gained by the sequential hydrolysis with Alcalase-GFNS and Flavourzyme-CCAFNS, which resulted in the formation of small hydrophobic and hydrophilic peptides, ≤5 kDa, confirmed by HPLC analysis and electrophoretic separation.     

Macrophage Immunomodulation Through New Polymers that Recapitulate Functional Effects of Itaconate as a Power House of Innate Immunity

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.     

Detailed microkinetic modelling of syngas to hydrocarbons via Fischer Tropsch synthesis over cobalt catalyst

Fuels production from syngas via Fischer Tropsch synthesis (FTs) is an alternative technology for clean energy production. The microkinetic model is a promising approach for gaining insight into FTs activity. In this study, a systematic microkinetic model was proposed to develop a process for cobalt-catalyzed FTs. All possible elementary reactions based on the carbide mechanism and characteristics of catalyst sites were considered in the kinetic model. The effects of the reaction rate constant, reaction pathways, and H₂ to CO ratio were represented by a kinetic parameter, reaction path, and operating parameter, respectively. The model could accurately predict product distribution trends, with an R² value and mean absolute relative residuals percentage of 0.91–0.93 and 5–43%, respectively, in comparison with experimental data. Hydrogen utilization was predicted and analyzed. High model accuracy was achieved, with a 10^?10–10^?3% error in the material balance.     

Whey valorization using transgalactosylation activity of immobilized β-galactosidase

Whey represents a significant dairy industry by-product that has recently received due attention based on the rich nutrient composition and significant transformation potential. Hereby, we investigated a possibility of whey lactose bioconversion into prebiotic compounds, galacto-oligosaccharides (GOS) using β-galactosidase transgalactosylation activity. The results showed that whey could be successfully used for GOS synthesis, since the highest GOS concentration (around 62 g L⁻¹) was obtained batchwise using 40% (w/w) sweet whey powder solution under optimum conditions (50°C, pH 4.5). Nevertheless, an efficient immobilized preparation using methacrylic Lifetech ECR8409 immobilization carrier was developed, enabling additional process improvement and ensuring at least 4 reaction cycles with unchanged yields and 2.5- fold enhanced productivity in comparison to the soluble enzyme. Therefore, this study provides a valuable contribution to the efficient and economical valorization of whey, which can be further on utilized as functional food and feed constituent.     

Storage technologies for wind power in the Columbia River Gorge

The transition from traditional energy sources to renewable has gained popularity and acceptance in recent years. This has been driven mainly by the current level of pollution, global warming, decommission of old nuclear power plants and the increasing cost of conventional energy sources. Nevertheless, one of the many steps to overcome is the seasonality or intermittency of renewable energy sources such as wind power. In recent years, new technologies have come up to address this problem, so the energy can be stored for future purposes. This paper analyses these energy storage alternatives for a specific case in the Columbia River Gorge for wind power. A hierarchical decision model is developed with criteria including political, social, environmental, technical and economical. The main conclusions highlight that the economical and technical criteria are among the most important ones for decision-makers.