Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Fas^lpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Fas^lpr, MRL-++, and previously generated Il6^−/− MRL-Fas^lpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Fas^lpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.     

Dietary fish oil and cytochrome P-450 monooxygenase activity in rat liver and kidney

Lauric acid hydroxylation and aminopyrineN-demethylation were studied in kidney and liver microsomes from rats treated with fish oil. Different doses of fish oil containing 20% eicosapentaenoic acid and 10% docosahexaenoic acid were provided daily to the rats for seven days. In all the groups studied, the lauric acid metabolism was higher in kidney microsomes and the aminopyrine metabolism in the liver microsomes. Although no effect on the renal cytochrome P-450 concentration was detectable, all four fish oil doses increased the hepatic concentration of cytochrome P-450 by a mean 27%. The higher fish oil doses used increased the renal and hepatic microsomal metabolism of aminopyrine. The lauric acid metabolism was increased by fish oil only in the liver. Fish oil, a known inducer of fatty acid peroxisomal β-oxidation, also induced microsomal activity. These results show that liver and kidney respond in different ways to dietary factors such as fish oil. In addition, our study would suggest that fish oil increased the activity of two different families of liver cytochrome P-450. The activity of kidney lauric acid 11- and 12-hydroxylation, however, was not modulated by fish oil.     

Improving the stability of lycopene Z-isomers in isomerised tomato extracts

Tomato-based foods rich in Z-lycopene are potentially more bioavailable and have greater bioefficacy compared to natural tomato products which mainly contain all-E-lycopene. To prepare a stable tomato extract with a high level of Z-lycopene, geometrical isomerisation of lycopene was studied in organic solvents either alone or in the presence of a tomato extract. Interconversion between the isomers was observed in all systems with 13Z-lycopene being the least stable. Heating a tomato extract containing mainly the all-E-isomer in ethyl acetate produced successively 13Z-, 9Z- and 5Z-lycopene. An isomerised tomato oleoresin with a minimal content of the most unstable 13Z-lycopene could be obtained by refluxing tomato oleoresin in ethyl acetate for 1 week. In this isomerised tomato oleoresin, total lycopene and lycopene isomer profiles were shown to remain constant for 1 year at room temperature. Accordingly, this product is a valid source of stable and potentially highly bioavailable lycopene.     

Microglial Extracellular Vesicles as Modulators of Brain Microenvironment in Glioma

Microglial cells represent the resident immune elements of the central nervous system, where they exert constant monitoring and contribute to preserving neuronal activity and function. In the context of glioblastoma (GBM), a common type of tumor originating in the brain, microglial cells deeply modify their phenotype, lose their homeostatic functions, invade the tumoral mass and support the growth and further invasion of the tumoral cells into the surrounding brain parenchyma. These modifications are, at least in part, induced by bidirectional communication among microglial and tumoral cells through the release of soluble molecules and extracellular vesicles (EVs). EVs produced by GBM and microglial cells transfer different kinds of biological information to receiving cells, deeply modifying their phenotype and activity and could represent important diagnostic markers and therapeutic targets. Recent evidence demonstrates that in GBM, microglial-derived EVs contribute to the immune suppression of the tumor microenvironment (TME), thus favoring GBM immune escape. In this review, we report the current knowledge on EV formation, biogenesis, cargo and functions, with a focus on the effects of microglia-derived EVs in GBM. What clearly emerges from this analysis is that we are at the beginning of a full understanding of the complete picture of the biological effects of microglial-derived EVs and that further investigations using multidisciplinary approaches are necessary to validate their use in GBM diagnosis and therapy.     

Comparative analysis of bacterial community composition in bulk tank raw milk by culture-dependent and culture-independent methods using the viability dye propidium monoazide

Microbial diversity of 3 raw milk samples after 72 h of storage at 4°C in a bulk tank was analyzed by culture-dependent and -independent methods. The culture-dependent approach was based on the isolation of bacteria on complex and selective media, chemotaxonomic differentiation of isolates, and subsequent identification by 16S rRNA gene sequencing. The culture-independent approach included the treatment of raw milk with the dye propidium monoazide before direct DNA extraction by mechanic and enzymatic cell lysis approaches, and cloning and sequencing of the 16S rRNA genes. The selective detection of viable bacteria improved the comparability between bacterial compositions of raw milk based on culture-dependent and -independent methods, which was the major objective of this study. Several bacterial species of the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria were detected by the culture-dependent method, whereas mainly bacteria of the phylum Proteobacteria as well as low proportions of the phyla Bacteroidetes and Actinobacteria were detected by the culture-independent method. This led to the conclusion that the phylum Firmicutes was strongly discriminated by the culture-independent approach. Generally, species richness detected by the culture-dependent method was higher than that detected by the culture-independent method for all samples. However, few taxa could be detected solely by the direct DNA-based method. In conclusion, the combination of culture-dependent and -independent methods led to the detection of the highest bacterial diversity for the raw milk samples analyzed. It was shown that DNA extraction from raw milk as the essential step in culture-independent methods causes the discrimination of taxa by incomplete cell lysis. Treatment of raw milk with the viability dye propidium monoazide was optimized for the application in raw milk without former removal of milk ingredients and proved to be a suitable tool to ensure comparability of bacterial diversity depicted by both methods.     

Nutritional modulation of insulin resistance in the true carnivorous cat: a review

Cats are strict carnivores that rely on nutrients in animal tissues to meet their specific and unique nutritional requirements. In their natural habitat, cats consume prey high in protein with moderate amounts of fat and minimal carbohydrates in contrast to commercial diets, which are sometimes moderate to high in carbohydrates. This change in diet has been accompanied by a shift from an outdoor environment to an indoor lifestyle and decreased physical activity, because cats no longer need to hunt to obtain food. This transformation of the lifestyle of cats is thought to be responsible for the recent increase in incidence of obesity, insulin resistance, and diabetes mellitus in domestic cats. At first, an overview of the evolutionary physiological adaptations of carbohydrate digestion in the feline digestive tract and of the hepatic carbohydrate and protein metabolism reflecting the true carnivorous nature of cats is given. Secondly, this literature review deals with nutritional modulation of insulin sensitivity, focusing on dietary macronutrients, carbohydrate sources, and dietary fiber for prevention and treatment of insulin resistance.     

Phenolic Oxime Oligomers Inhibit Alzheimer's Amyloid Fibril Formation and Disaggregate Fibrils In Vitro

See you later amyloid β : A screen of a small library of oxime oligomers with an HTS fluorescence assay for amyloid fibril inhibition and subsequent investigation by atomic force microscopy revealed two new micromolar inhibitors of amyloid fibril formation. These new inhibitors have IC₅₀ values in the 10 μM range.

     

Macrocell corrosion of steel in concrete: Characterization of anodic behavior in relation to the chloride content

This study presents the determination of electrochemical properties of active steel in mortar, based on inverse numerical modeling that focuses on their dependency on chloride content. An experimental campaign, consisting of galvanic coupling tests between anode samples contaminated with different chloride concentrations and cathode samples without chlorides, was carried out. Cathode polarization tests allowed for directly determining passive steel electrochemical parameters. Anode polarization tests coupled with a numerical optimization were then performed for quantifying active steel parameters and focusing on chloride's effect on the iron anodic Tafel coefficient. Furthermore, the steel electrochemical properties were successfully used as input parameters to model the galvanic experiments.