Search results for " mouse"

P092 Exogenous administration of IL-4-treated macrophages prevents intestinal fibrosis in Stat6 knockout mice

2017

The LDL receptor in the retina: the missing link in aging, the new target in dietary prevention

2012

National audience; Purpose: The discovery of the LDL receptor (LDLR) in 1985 by Brown and Goldstein was awarded by a Nobel Prize. The LDLR has initially been identified for its role in mediating the endocytosis of LDL particles in the vascular endothelium. The deposition of lipids, including cholesterol and cholesteryl esters in Bruch’s Membrane in the one hand, and in the vessel intima in the other hand, is one of the common features of age related macular degeneration (AMD) and cardiovascular disease (CVD). Dietary habits with high intakes of omega 3 long chain fatty acids (LCFA) have been associated with AMD prevention. Similar effects have been demonstrated in CVD prevention. The mechan…

2014

TGF- β is a highly pleiotropic cytokine and a well-known suppressor of inflammatory T cells. Dysregulation in TGF- β function is associated with multiple pathological phenomenons including tumor cell growth, fibrosis and autoimmunity. GARP (glycoprotein A repetitions predominant) is an activation maker on human regulatory T cells (Treg) which is known to modulate the bioavailability of TGF- β . To address the cell-independent regulatory capacity of GARP we generated a soluble GARP protein (sGARP). Interestingly, T cells cultured in presence of sGARP showed SMAD2/3 phosphorylation similar to TGF- β treated T cells. In addition, sGARP function was inhibited by blockade of TGF- β -signaling, s…

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

2023

AbstractThe historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time …

Gastric emptying, small intestinal transit and fecal output in dystrophic (mdx) mice.

2009

Duchenne muscular dystrophy (DMD), which results from deficiency in dystrophin, a sarcolemma protein of skeletal, cardiac and smooth muscle, is characterized by progressive striated muscle degeneration, but various gastrointestinal clinical manifestations have been observed. The aim was to evaluate the possible impact of the dystrophin loss on the gastrointestinal propulsion in mdx mice (animal model for DMD). The gastric emptying of a carboxymethyl cellulose/phenol red dye non-nutrient meal was not significantly different at 20 min from gavaging between wild-type and mdx mice. The intestinal transit and the fecal output were significantly decreased in mdx versus normal animals, although th…

Deficiency of Nrf2 accelerates the effector phase of arthritis and aggravates joint disease

2011

14 páginas, 8 figuras, 1 tabla.-- et al.

Duchenne Muscular Dystrophy (DMD): Should it be Considered a Systemic Disease?

2016

Duchenne muscular dystrophy (DMD) is an X-linked muscle disease characterized by progressive skeletal muscle loss and development of respiratory failure due to involvement of respiratory muscles. Similar to human DMD, the mdx mouse model lacks dystrophin but is characterized by relatively mild muscle injury, allowing testing the effects of mild endurance exercise training on dystrophic skeletal muscle. We were interested to study the effects of exercise training on airway cells in trained mdx mice by applying the same protocol previously tested in Swiss mice. We found that mdx mice showed little airway inflammation associated with training, but developed increasing apoptosis of airway cells…

Combined effect of AAV-U7-induced dystrophin exon skipping and soluble activin Type IIB receptor in mdx mice.

2012

Adeno-associated virus (AAV)-U7-mediated skipping of dystrophin-exon-23 restores dystrophin expression and muscle function in the mdx mouse model of Duchenne muscular dystrophy. Soluble activin receptor IIB (sActRIIB-Fc) inhibits signaling of myostatin and homologous molecules and increases muscle mass and function of wild-type and mdx mice. We hypothesized that combined treatment with AAV-U7 and sActRIIB-Fc may synergistically improve mdx muscle function. Bioactivity of sActRIIB-Fc on skeletal muscle was first demonstrated in wild-type mice. In mdx mice we show that AAV-U7-mediated dystrophin restoration improved specific muscle force and resistance to eccentric contractions when applied a…

Changes in spinal range of motion after a flexibility training program in elderly women

2014

Giuseppe Battaglia,1,2 Marianna Bellafiore,1,2 Giovanni Caramazza,2 Antonio Paoli,3 Antonino Bianco,1,2 Antonio Palma1,2 1Department of Law, Society, and Sport Sciences, University of Palermo, Palermo, Italy; 2Sicilian Regional Sports School of Italian National Olympic Committee (CONI), Sicily, Italy; 3Department of Biomedical Sciences, University of Padova, Padova, Italy Background: Aging-related reduced spinal mobility can interfere with the execution of important functional skills and activities in elderly women. Although several studies have shown positive outcomes in response to spinal flexibility training programs, little is known about the management of sets and repetitions in traini…

Design, Synthesis, Chemical and Biochemical Insights Into Novel Hybrid Spirooxindole-Based p53-MDM2 Inhibitors With Potential Bcl2 Signaling Attenuat…

2021

The tumor resistance to p53 activators posed a clinical challenge. Combination studies disclosed that concomitant administration of Bcl2 inhibitors can sensitize the tumor cells and induce apoptosis. In this study, we utilized a rapid synthetic route to synthesize two novel hybrid spirooxindole-based p53-MDM2 inhibitors endowed with Bcl2 signaling attenuation. The adducts mimic the thematic features of the chemically stable potent spiro [3H-indole-3,2′-pyrrolidin]-2(1H)-ones p53-MDM2 inhibitors, while installing a pyrrole ring via a carbonyl spacer inspired by the natural marine or synthetic products that efficiently inhibit Bcl2 family functions. A chemical insight into the two synthesized…