Search results for "Induced"

Restoration of perivascular adipose tissue function in diet-induced obese mice without changing bodyweight

2017

Background and Purpose We have recently shown that a reduced function of endothelial nitric oxide synthase (eNOS) in the perivascular adipose tissue (PVAT) contributes crucially to obesity-induced vascular dysfunction in mice. The current study was conducted to test the hypothesis that vascular dysfunction in obesity can be reversed by in vivo improvement of PVAT eNOS activity. Experimental Approach Male C57BL/6 J mice were fed a high-fat diet (HFD) for 22 weeks to induce obesity. During the last 4 weeks of HFD feeding, the obese mice were treated orally with the standardized Crataegus extract WS® 1442 which has been shown previously to improve eNOS activity. Key Results Diet-induced obesit…

External Influences on Invertebrate Brain Histamine and Related Compounds via an Automated Derivatization Method for Capillary Electrophoresis.

2017

8 pages; International audience; Histamine has been shown to modulate visual system and photic behavior in arthropods. However, few methods are available for the direct quantification of histamine and its precursor and metabolites in arthropod brain. In this work, a method for the separation of histamine, its precursor histidine, and its metabolite N-methyl-histamine from brain extracts of a freshwater crustacean has been developed using capillary electrophoresis with laser-induced fluorescence detection. Molecules were tagged on their primary amine function with naphthalene-2,3-dicarboxaldehyde, but derivatized histamine and N-methyl-histamine exhibited poor stability in contrast to deriva…

Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake

2017

The extracellular effects of the endocannabinoids anandamide and 2-arachidonoyl glycerol are terminated by enzymatic hydrolysis after crossing cellular membranes by facilitated diffusion. The lack of potent and selective inhibitors for endocannabinoid transport has prevented the molecular characterization of this process, thus hindering its biochemical investigation and pharmacological exploitation. Here, we report the design, chemical synthesis, and biological profiling of natural product-derived N-substituted 2,4-dodecadienamides as a selective endocannabinoid uptake inhibitor. The highly potent (IC50 = 10 nM) inhibitor N-(3,4-dimethoxyphenyl)ethyl amide (WOBE437) exerted pronounced canna…

Metformin decreases progerin expression and alleviates pathological defects of Hutchinson–Gilford progeria syndrome cells

2016

Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disorder that causes systemic accelerated aging in children. This syndrome is due to a mutation in the LMNA gene that leads to the production of a truncated and toxic form of lamin A called progerin. Because the balance between the A-type lamins is controlled by the RNA-binding protein SRSF1, we have hypothesized that its inhibition may have therapeutic effects for HGPS. For this purpose, we evaluated the antidiabetic drug metformin and demonstrated that 48 h treatment with 5 mmol/l metformin decreases SRSF1 and progerin expression in mesenchymal stem cells derived from HGPS induced pluripotent stem cells (HGPS MSCs). The effect …

Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathw…

2018

AbstractHutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that leads to premature aging. In this study, we used induced pluripotent stem cells to investigate the hypopigmentation phenotypes observed in patients with progeria. Accordingly, two iPS cell lines were derived from cells from HGPS patients and differentiated into melanocytes. Measurements of melanin content revealed a lower synthesis of melanin in HGPS melanocytes as compared to non-pathologic cells. Analysis of the melanosome maturation process by electron microscopy revealed a lower percentage of mature, fully pigmented melanosomes. Finally, a functional rescue experiment revealed the direct role of progerin…

Transcriptomic study of the toxic mechanism triggered by beauvericin in Jurkat cells

2018

Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5 mu M; 24 h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations. Gene ontology (GO) analysis showed several biological processes related to electron transport chain, oxidative phosphorylation, and cel…

Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation

2017

International audience; Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group). Spontaneously breathing and MV untreated infected animals (n = 11 in each group), as well as uninfected animals (n = 5 in each group) were used as controls. Microbiological features and inflammation were evaluated. Data are presented as medians (interquartile range). Linezolid a…

Generation of three human iPSC lines from PLAN (PLA2G6-associated neurodegeneration) patients

2021

© 2021 The Authors.

2017

Brain microvascular endothelial cells (BMEC) separate the peripheral blood from the brain. These cells, which are surrounded by basal lamina, pericytes and glial cells, are highly interconnected through tight and gap junctions. Their permeability properties restrict the transfer of potentially useful therapeutic agents. In such a hermetic system, the gap junctional exchange of small molecules between cerebral endothelial and non-endothelial cells is crucial for maintaining tissue homeostasis. MicroRNA were shown to cross gap junction channels, thereby modulating gene expression and function of the recipient cell. It was also shown that, when altered, BMEC could be regenerated by endothelial…

Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells

2018

SUMMARY Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells. In contrast, ciliopathy patient-derived iPSC-RPE and iPSC-RPE with a knockdown of ciliary-trafficking pr…