Search results for "NBR"
showing 10 items of 2710 documents
Moderate exercise in mice improves cancer plus chemotherapy-induced muscle wasting and mitochondrial alterations
2019
Cancer cachexia is a multifactorial syndrome characterized by anorexia, body wasting, and muscle and adipose tissue loss, impairing patient's tolerance to anticancer treatments and survival. The aim of the present study was to compare the effects induced in mice by tumor growth alone (C26) or in combination with chemotherapy [C26 oxaliplatin and 5-fluorouracil (oxfu)] and to evaluate the potential of moderate exercise. Oxfu administration to C26 mice exacerbated muscle wasting and triggered autophagy or mitophagy, decreased protein synthesis, and induced mitochondrial alterations. Exercise in C26 oxfu mice counteracted the loss of muscle mass and strength, partially rescuing autophagy and m…
miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma
2020
Multiple myeloma (MM) is tightly dependent on inflammatory bone marrow microenvironment. IL-17 producing CD4+ T cells (Th17) sustain MM cells growth and osteoclasts-dependent bone damage. In turn, Th17 differentiation relies on inflammatory stimuli. Here, we investigated the role of miR-21 in Th17-mediated MM tumor growth and bone disease. We found that early inhibition of miR-21 in naive T cells (miR-21i-T cells) impaired Th17 differentiation in vitro and abrogated Th17-mediated MM cell proliferation and osteoclasts activity. We validated these findings in NOD/SCID-g-NULL mice, intratibially injected with miR-21i-T cells and MM cells. A Pairwise RNAseq and proteome/phosphoproteome analysis…
Germinal Centers Determine the Prognostic Relevance of Tertiary Lymphoid Structures and Are Impaired by Corticosteroids in Lung Squamous Cell Carcino…
2018
Abstract In solid tumors, the presence of lymph node–like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS develop in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multispectral microscopy, quantitative pathology, and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation…
Blockade of nitric oxide signalling promotes resilience to the effects of social defeat stress on the conditioned rewarding properties of MDMA in mice
2020
Abstract MDMA abuse continues being a serious problem in our society. Environmental factors, such as stress, increase the vulnerability of individuals to develop drug abuse and we have observed that exposure to social defeat (SD) stress alters the sensitivity of mice to the rewarding effects of MDMA in the conditioned place preference (CPP) paradigm. In the present study, we evaluated the role of the nitric oxide (NO) pathway in the effects of SD on the rewarding properties of MDMA. Three groups of mice were treated with an inhibitor of NO synthesis, 7-nitroindazole (0, 7.25 and 12.5 mg/kg), before each exposure to SD and place conditioning with MDMA (1.25 mg/kg) on PND 54, 56, 58, and 60. …
Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner
2016
ABSTRACT Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wil…
Cross-Talk between Myeloid-Derived Suppressor Cells and Mast Cells Mediates Tumor-Specific Immunosuppression in Prostate Cancer.
2018
Abstract Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell–deficient KitWsh mice. TRAMP mice are tolerant to the SV40 Large T antigen, which is o…
Rhythmic Regulation of Photoreceptor and RPE Genes Important for Vision and Genetically Associated With Severe Retinal Diseases.
2018
Purpose The aim of the present study was to identify candidate genes for mediating daily adjustment of vision. Methods Genes important for vision and genetically associated with severe retinal diseases were tested for 24-hour rhythms in transcript levels in neuronal retina, microdissected photoreceptors, photoreceptor-related pinealocytes, and retinal pigment epithelium-choroid (RPE-choroid) complex by using quantitative PCR. Results Photoreceptors of wildtype mice display circadian clock-dependent regulation of visual arrestins (Arr1, Arr4) and the visual cycle gene Rdh12, whereas cells of the RPE-choroid exhibit light-dependent regulation of the visual cycle key genes Lrat, Rpe65, and Rdh…
Silencing of hepatic fate-conversion factors induce tumorigenesis in reprogrammed hepatic progenitor-like cells
2016
Abstract Background Several studies have reported the direct conversion of mouse fibroblasts to hepatocyte-like cells with different degrees of maturation by expression of hepatic fate-conversion factors. Methods We have used a combination of lentiviral vectors expressing hepatic fate-conversion factors with Oct4, Sox2, Klf4, and Myc to convert mouse embryonic fibroblasts into hepatic cells. Results We have generated hepatic cells with progenitor-like features (iHepL cells). iHepL cells displayed basic hepatocyte functions but failed to perform functions characteristic of mature hepatocytes such as significant Cyp450 or urea cycle activities. iHepL cells expressed multiple hepatic-specific …
CD16+ Macrophages Mediate Fibrosis in Inflammatory Bowel Disease.
2017
Background and Aims Fibrosis is a common complication of Crohn's disease [CD], and is related to dysregulated tissular repair following inflammation, in which macrophages play a central role. We have previously observed that STAT6-/- mice present delayed mucosal recovery after 2,4,6-trinitrobenzenesulfonic acid [TNBS]-induced colitis due to a deficiency in reparatory interleukin-4 [IL4]/STAT6-dependent M2 macrophages, which can be reverted by the exogenous transfer of this cell type. In the present study, we analyse the role of STAT6-dependent macrophages in intestinal fibrosis. Methods Colitis was induced by weekly intra-rectal administration of TNBS [6 weeks] to STAT6-/- mice and wild-typ…
General control non-derepressible 2 (GCN2) in T cells controls disease progression of autoimmune neuroinflammation.
2016
Relapsing-remitting multiple sclerosis (MS)(2) is characterized by phases of acute neuroinflammation followed by spontaneous remission. Termination of inflammation is accompanied by an influx of regulatory T cells (Tregs).(3) The molecular mechanisms responsible for directing Tregs into the inflamed CNS tissue, however, are incompletely understood. In an MS mouse model we show that the stress kinase general control non-derepressible 2 (GCN2),(4) expressed in T cells, contributes to the resolution of autoimmune neuroinflammation. Failure to recover from acute inflammation was associated with reduced frequencies of CNS-infiltrating Tregs. GCN2 deficient Tregs displayed impaired migration to a…