Search results for "acids"
showing 10 items of 3520 documents
A Phase II Study of the Histone Deacetylase Inhibitor Panobinostat (LBH589) in Pretreated Patients with Small-Cell Lung Cancer
2013
Background: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors. Methods: This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1–8) every 21 days. Results: A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1–6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 3…
Exosomal and Plasma Non-Coding RNA Signature Associated with Urinary Albumin Excretion in Hypertension
2022
Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, plays important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways. Three individual libraries (plasma and urinary exosomes, and total plasma) were prepared from each hypertensive patient (with or without albuminuria) for ncRNA sequencing analysis. Next, an RNA-based transcriptional regulatory network was constructed. The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piR…
The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons.
2015
The molecular composition of the cannabinoid type 1 (CB1) receptor complex beyond the classical G-protein signaling components is not known. Using proteomics on mouse cortex in vivo, we pulled down proteins interacting with CB1 in neurons and show that the CB1 receptor assembles with multiple members of the WAVE1 complex and the RhoGTPase Rac1 and modulates their activity. Activation levels of CB1 receptor directly impacted on actin polymerization and stability via WAVE1 in growth cones of developing neurons, leading to their collapse, as well as in synaptic spines of mature neurons, leading to their retraction. In adult mice, CB1 receptor agonists attenuated activity-dependent remodeling o…
Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells
2009
Immunological tolerance is one of the fundamental aspects of the immune system. The CD4(+)CD25(+) regulatory T (Treg) cells have emerged as key players in the development of tolerance to self and foreign antigens. However, little is known about the endogenous factors and mechanisms controlling their suppressive capacity on immune response. In this study, we observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, diminished, in a dose-dependent manner, the capacity of Treg cells to inhibit the CD4(+)CD25(-) effector T-cell proliferation. DHA not only reduced the migration of Treg cells toward chemokines but also downregulated the mRNA expression of CCR-4 and CXCR-4 in Tr…
Induction of RAGE Shedding by Activation of G Protein-Coupled Receptors
2011
The multiligand Receptor for Advanced Glycation End products (RAGE) is involved in various pathophysiological processes, including diabetic inflammatory conditions and Alzheimers disease. Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. Moreover, administration of recombinant soluble RAGE suppresses activation of cell surface-located RAGE by trapping RAGE ligands. Therefore stimulation of RAGE shedding might have a therapeutic value regarding inflammatory diseases. We aimed to investigate whether RAGE shedding is inducible via ligand-induced activation of G protein-coupled recep…
Chronic restraint stress and chronic corticosterone treatment modulate differentially the expression of molecules related to structural plasticity in…
2004
Stress and stress-related hormones induce structural changes in neurons of the adult CNS. Neurons in the hippocampus, the amygdala and the prefrontal cortex undergo neurite remodeling after chronic stress. In the hippocampus some of these effects can be mimicked with chronic administration of adrenal steroids. These changes in neuronal structure may be mediated by certain molecules related to plastic events such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). The expression of PSA-NCAM persists in the adult hippocampus and it is up-regulated after chronic stress. The piriform cortex also displays considerable levels of PSA-NCAM during adulthood and indirect evide…
A two-year follow-up of oral antioxidant supplementation in primary open-angle glaucoma: an open-label, randomized, controlled trial
2014
Purpose To evaluate the effect of oral antioxidant supplementation (OAS) on primary open-angle glaucoma (POAG) over a 2-year follow-up period. Patients and methods In this open-label, randomized controlled trial, 117 eyes of 117 patients with mild or moderate POAG and intraocular pressure under control with topical antiglaucoma medications were recruited and randomly divided into three groups according to supplementation: (1) OAS with (ICAPS R® – Alcon Laboratories, n = 26); (2) OAS without ω-3 fatty acids (OFTAN MACULA® – Laboratorios Esteve, n = 28); and (3) a control group without OAS (n = 63). They all underwent visual field (VF) tests (Humphrey 24-2) and scans using a Fourier-domain op…
Retinas of the Diurnal RodentArvicanthis ansorgeiAre Highly Resistant to Experimentally Induced Stress and Degeneration
2011
International audience; PURPOSE. Environmentally induced stress plays a significant role in retinal degeneration and blindness both in animals and in humans. Among such sources of stress, phototoxicity is well studied and has been shown to lead to photoreceptor-specific loss in a number of species. However, the vast majority of studies have been conducted in nocturnal, albino rod-dominant rat and mouse strains, and the pertinence of such findings to human pathology and cone loss is debatable. The authors examined retinal vulnerability to damage in the diurnal murid rodent Arvicanthis ansorgei, a pigmented species with a large number of cones. METHODS. The authors used established protocols …
Intravitreal Docosahexaenoic Acid in a Rabbit Model: Preclinical Safety Assessment
2014
PurposeThe purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period.MethodsSixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week a…
Deregulation of dicer and mir-155 expression in liposarcoma
2015
Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versu…