Search results for "MICE"
showing 10 items of 6027 documents
Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls
2018
In this study, we report the development of a dual extraction protocol for RNA and lipids, including phospholipids, endocannabinoids, and arachidonic acid, at high spatial resolution, e.g., brain punches obtained from whole frozen brains corresponding to four brain subregions: dorsal hippocampus, ventral hippocampus, basolateral amygdala, and hypothalamus. This extraction method combined with LC/multiple reaction monitoring for lipid quantification and quantitative PCR for RNA investigation allows lipidomic and transcriptomic profiling from submilligram amounts of tissue, thus benefiting the time and animal costs for analysis and the data reliability due to prevention of biological variabil…
In Vitro Biocompatibility Evaluation of Nine Dermal Fillers on L929 Cell Line
2020
Objective. Biomaterial research for soft tissue augmentation is an increasing topic in aesthetic medicine. Hyaluronic acid (HA) fillers are widely used for their low invasiveness and easy application to correct aesthetic defects or traumatic injuries. Some complications as acute or chronic inflammation can occur in patients following the injection. Biocompatibility assays are required for medical devices intended for human use, in order to prevent damages or injuries in the host. In this study, nine HA fillers were tested in order to evaluate their cytotoxicity and their effects on L929 cell line, according to the UNI EN ISO 10993 regulation. Methods. Extracts were prepared from nine HA fil…
Ticket to Ride: Targeting Proteins to Exosomes for Brain Delivery.
2017
Exosomes represent an attractive vehicle for the delivery of biomolecules. However, mechanisms for loading functional molecules into exosomes are relatively unexplored. Here we report the use of the evolutionarily conserved late-domain (L-domain) pathway as a mechanism for loading exogenous proteins into exosomes. We demonstrate that labeling of a target protein, Cre recombinase, with a WW tag leads to recognition by the L-domain-containing protein Ndfip1, resulting in ubiquitination and loading into exosomes. Our results show that Ndfip1 expression acts as a molecular switch for exosomal packaging of WW-Cre that can be suppressed using the exosome inhibitor GW4869. When taken up by floxed …
Dextran-based therapeutic nanoparticles for hepatic drug delivery.
2016
Aim: Evaluation of dextran-based nanoparticles (DNP) as a drug delivery system to target myeloid cells of the liver. Materials & methods: DNP were synthesized and optionally PEGylated. Their toxicity and cellular uptake were studied in vitro. Empty and siRNA-carrying DNP were tested in vivo with regard to biodistribution and cellular uptake. Results: In vitro, DNP were taken up by cells of the myeloid lineage without compromising their viability. In vivo, empty and siRNA-carrying DNP distributed to the liver where a single treatment addressed approximately 70% of macrophages and dendritic cells. Serum parameters indicated no in vivo toxicity. Conclusion: DNP are multifunctional liver-s…
Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles
2016
Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes…
Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis
2018
Summary Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional respons…
Characterization of a Fetal Liver Cell Population Endowed with Long-Term Multiorgan Endothelial Reconstitution Potential.
2016
et al.
Cell type specific impact of cannabinoid receptor signaling in somatosensory barrel map formation in mice
2019
Endocannabinoids and their receptors are highly abundant in the developing cerebral cortex and play major roles in early developmental processes, for example, neuronal proliferation, migration, and axonal guidance as well as postnatal plasticity. To investigate the role of the cannabinoid type 1 receptor (CB1) in the formation of sensory maps in the cerebral cortex, the topographic representation of the whiskers in the primary somatosensory cortex (barrel field) of adult mice with different cell type specific genetic deletion of CB1 was studied. A constitutive absence of CB1 (CB1-KO) significantly decreased the total area of the somatosensory cortical map, affecting barrel, and septal areas…
Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
2017
Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Latvia, Riga, Latvia; 4Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania Purpose: Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors.…
Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
2020
TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify structure and function of the Golgi apparatus, culminating in the increased release of a pro-malignant secretome by tumor cells and primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting with the hypoxia responsive factor HIF1α, mutant p53 induces the expression of miR-30d, which in turn causes tubulo-vesiculation of the Golgi apparatus, leading …