Search results for "Activation"
showing 10 items of 2079 documents
Synergistic activation of AMPK prevents from polyglutamine-inducedtoxicity inCaenorhabditis elegans
2020
11 páginas, 4 figuras. Supplementary material related to this article can be found, in the online version, at doi: https://doi.org/10.1016/j.phrs.2020.105105.
Analysis of nucleophosmin–anaplastic lymphoma kinase (NPM‐ALK)‐reactive CD8+ T cell responses in children with NPM‐ALK+ anaplastic large cell lymphoma
2016
Summary Cellular immune responses against the oncoantigen anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) have been detected using peptide-based approaches in individuals preselected for human leucocyte antigen (HLA)-A*02:01. In this study, we aimed to evaluate nucleophosmin (NPM)-ALK-specific CD8+ T cell responses in ALCL patients ensuring endogenous peptide processing of ALK antigens and avoiding HLA preselection. We also examined the HLA class I restriction of ALK-specific CD8+ T cells. Autologous dendritic cells (DCs) transfected with in-vitro-transcribed RNA (IVT-RNA) encoding NPM–ALK were used as antigen-presenting cells for T cell …
Cognitive network hyperactivation and motor cortex decline correlate with ALS prognosis.
2021
We aimed to quantitatively characterize progressive brain network disruption in Amyotrophic Lateral Sclerosis (ALS) during cognition using the mismatch negativity (MMN), an electrophysiological index of attention switching. We measured the MMN using 128-channel EEG longitudinally (2-5 timepoints) in 60 ALS patients and cross-sectionally in 62 healthy controls. Using dipole fitting and linearly constrained minimum variance beamforming we investigated cortical source activity changes over time. In ALS, the inferior frontal gyri (IFG) show significantly lower baseline activity compared to controls. The right IFG and both superior temporal gyri (STG) become progressively hyperactive longitudina…
The JAK2 pathway is activated in idiopathic pulmonary fibrosis
2018
Background: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (ATII), thereby contributing to lung fibrosis in IPF. Although activation of Janus kinase 2 (JAK2) has been implicated in proliferative disorders, its role in IPF is unknown. The aim of this study was to analyze JAK2 activation in IPF, and to determine whether JAK2/STAT3 inhibition is a potential therapeutic strategy for this disease. Methods and results: JAK2/p-JAK2 and STAT3/pSTAT3 expression was evaluated using quantitative …
Kinetics of the early development of uniparental human haploid embryos
2016
Objective: To describe morphokinetically the early development of human haploid parthenotes and androgenotes and to compare them with euploid embryos. Design: Experimental study of kinetics. Setting: University-affiliated private fertility center. Patient(s): Experimental haploid parthenotes and androgenotes. Intervention(s): Kinetic study of early development (up to eight cells) of 8 parthenotes, 10 androgenotes, and 20 euploid embryos. Main Outcome Measure(s): Timing of the first seven cleavages determined according to embryo origin, then calculation of the duration of the second and third cell cycles (cc2 and cc3) of whole embryos and individual cells. Result(s): Parthenotes and androgen…
β-Lactoglobulin Heptapeptide Reduces Oxidative Stress in Intestinal Epithelial Cells and Angiotensin II-Induced Vasoconstriction on Mouse Mesenteric …
2019
Peptides derived from buffalo dairy products possess multiple healthy properties that cannot be exerted as long as they are encrypted in parent proteins. To evaluate the biological activities of encrypted peptide sequences from buffalo ricotta cheese, we performed a simulated gastrointestinal (GI) digestion. Chemical and pharmacological characterization of the digest led to the identification of a novel peptide endowed with antioxidant and antihypertensive action. The GI digest was fractionated by Semiprep-HPLC, and fractions were tested against reactive oxygen species (ROS) release in an H2O2-treated intestinal epithelial cell line. UHPLC-PDA-MS/MS analysis revealed the presence of an abun…
From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by “inflamm-ageing”
2017
Ageing is a complex process characterized by a general decline in physiological functions with increasing morbidity and mortality. The most important aspect of ageing is the chronic inflammatory status, named âinflamm-ageingâ, strictly associated with the deterioration of the immune function, termed âimmunosenescenceâ. Both are causes of increased susceptibility of elderly to infectious diseases, cancer, dementia, cardiovascular diseases and autoimmunity, and of a decreased response to vaccination. It has been widely demonstrated that ageing has a strong impact on the remodelling of the B cell branch of immune system. The first evident effect is the significant decrease in circulati…
Targeting the Endoplasmic Reticulum Unfolded Protein Response to Counteract the Oxidative Stress-Induced Endothelial Dysfunction
2017
In endothelial cells, the tight control of the redox environment is essential for the maintenance of vascular homeostasis. The imbalance between ROS production and antioxidant response can induce endothelial dysfunction, the initial event of many cardiovascular diseases. Recent studies have revealed that the endoplasmic reticulum could be a new player in the promotion of the pro- or antioxidative pathways and that in such a modulation, the unfolded protein response (UPR) pathways play an essential role. The UPR consists of a set of conserved signalling pathways evolved to restore the proteostasis during protein misfolding within the endoplasmic reticulum. Although the first outcome of the U…
Decreased bioavailability of nitric oxide in aorta from ovariectomized senescent mice. Role of cyclooxygenase.
2015
This study investigates the effects of aging and/or ovariectomy on vascular reactivity to thromboxane A2 (TXA2) receptor stimulation with U46619, and the modulation by nitric oxide (NO) and cyclooxygenase (COX) in aorta from female senescence-accelerated mice (SAMP8) and from senescence resistant mice (SAMR1). Five-month-old female SAMR1 and SAMP8 were divided into three groups: sham-operated, ovariectomized and ovariectomized plus estradiol. Twenty-eight days after surgery, thoracic aortic rings were mounted for isometric recording of tension and concentration-response curves for U46619 (10(-10)-3 × 10(-7) M) were performed in the absence and in the presence of the NO synthase inhibitor N(…
Longevity-related molecular pathways are subject to midlife “switch” in humans
2019
Emerging evidence indicates that molecular aging may follow nonlinear or discontinuous trajectories. Whether this occurs in human neuromuscular tissue, particularly for the noncoding transcriptome, and independent of metabolic and aerobic capacities, is unknown. Applying our novel RNA method to quantify tissue coding and long noncoding RNA (lncRNA), we identified ~800 transcripts tracking with age up to ~60 years in human muscle and brain. In silico analysis demonstrated that this temporary linear “signature” was regulated by drugs, which reduce mortality or extend life span in model organisms, including 24 inhibitors of the IGF‐1/PI3K/mTOR pathway that mimicked, and 5 activators that oppos…