Organotypic Hippocampal Slice Cultures from Adult Tauopathy Mice and Theragnostic Evaluation of Nanomaterial Phospho-TAU Antibody-Conjugates.

Organotypic slice culture models surpass conventional in vitro methods in many aspects. They retain all tissue-resident cell types and tissue hierarchy. For studying multifactorial neurodegenerative diseases such as tauopathies, it is crucial to maintain cellular crosstalk in an accessible model system. Organotypic slice cultures from postnatal tissue are an established research tool, but adult tissue-originating systems are missing, yet necessary, as young tissue-originating systems cannot fully model adult or senescent brains. To establish an adult-originating slice culture system for tauopathy studies, we made hippocampal slice cultures from transgenic 5-month-old hTau.P301S mice. In addition to the comprehensive characterization, we set out to test a novel antibody for hyperphosphorylated TAU (pTAU, B6), with and without a nanomaterial conjugate. Adult hippocampal slices retained intact hippocampal layers, astrocytes, and functional microglia during culturing. The P301S-slice neurons expressed pTAU throughout the granular cell layer and secreted pTAU to the culture medium, whereas the wildtype slices did not. Additionally, cytotoxicity and inflammation-related determinants were increased in the P301S slices. Using fluorescence microscopy, we showed target engagement of the B6 antibody to pTAU-expressing neurons and a subtle but consistent decrease in intracellular pTAU with the B6 treatment. Collectively, this tauopathy slice culture model enables measuring the extracellular and intracellular effects of different mechanistic or therapeutic manipulations on TAU pathology in adult tissue without the hindrance of the blood-brain barrier.

Associations of altered hepatic gene expression in American lifestyle-induced obesity syndrome diet-fed mice with metabolic changes during NAFLD development and progression.

Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains poorly understood due to the complex metabolic and inflammatory changes in the liver. This study aimed to elucidate hepatic events related to inflammation and lipid metabolism and their linkage with metabolic alterations during NAFLD in American lifestyle-induced obesity syndrome (ALIOS) diet-fed mice. Forty-eight C57BL/6J male mice were fed with ALIOS diet (n=24) or control chow diet (n=24) for 8, 12, and 16 weeks. At the end of each timepoint, eight mice were sacrificed where plasma and liver were collected. Hepatic fat accumulation was followed using magnetic resonance imaging and confirmed with histology. Further, targeted gene expression and non-targeted metabolomics analysis were conducted. Our results showed higher hepatic steatosis, body weight, energy consumption, and liver mass in ALIOS diet-fed mice compared to control mice. ALIOS diet altered expression of genes related to inflammation (Tnfa and IL-6) and lipid metabolism (Cd36, Fasn, Scd1, Cpt1a, and Ppara). Metabolomics analysis indicated decrease of lipids containing polyunsaturated fatty acids such as LPE(20:5) and LPC(20:5) with increase of other lipid species such as LPI(16:0) and LPC(16:2) and peptides such as alanyl-phenylalanine and glutamyl-arginine. We further observed novel correlations between different metabolites including sphingolipid, lysophospholipids, peptides, and bile acid with inflammation, lipid uptake and synthesis. Together with the reduction of antioxidant metabolites and gut microbiota-derived metabolites contribute to NAFLD development and progression. The combination of non-targeted metabolomics with gene expression in future studies can further identify key metabolic routes during NAFLD which could be the targets of potential novel therapeutics.

Potential of Probiotic Frozen Blackcurrant Products: Consumer Preference, Physicochemical Characterization, and Cell Viability.

Blackcurrant is a healthy, affordable, and traditionally gardened berry that, thus far, has been underused in food applications. From the consumers' point of view, the acidic taste of blackcurrants is a challenge; therefore, these berries have mainly been utilized for sugary juice production. This research study aimed to develop a frozen vegan blackcurrant product with pleasant sensory properties and potential probiotic function. A candidate probiotic, Lactoplantibacillus plantarum Q823, was used in the manufacturing process. The physicochemical properties, nutritional composition, and consumer preference for the developed product were assessed, as was the viability of L. plantarum Q823 during storage time and in an in vitro gastrointestinal model. Consumers (n = 71) perceived the developed product to be pleasant. L. plantarum Q823 had high viability counts (log colony forming units (cfu) g-1 7.0 ± 0.38) in the final product, although the viability of L. plantarum Q823 during storage time needs to be enhanced to obtain a probiotic product. Thus, within an optimized formulation, blackcurrant berries represent a potential raw material for functional frozen food products.

Biocompatible hydrogelators based on bile acid ethyl amides.

Four novel bile acid ethyl amides were synthetized using a well-known method. All the four compounds were characterized by IR, SEM, and X-ray crystal analyses. In addition, the cytotoxicity of the compounds was tested. Two of the prepared compounds formed organogels. Lithocholic acid derivative 1 formed hydrogels as 1% and 2% (w/v) in four different aqueous solutions. This is very intriguing regarding possible uses in biomedicine.