Search results for "mit"
showing 10 items of 11910 documents
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…
5-HT1A Receptor Function Makes Wound Healing a Happier Process
2018
Skin wound healing is a multistage phenomenon that is regulated by cell–cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis reve…
Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles.
2018
Abstract Background Virtually all cell types have the capacity to secrete nanometer-sized extracellular vesicles, which have emerged in recent years as potent signal transducers and cell-cell communicators. The multifunctional protein Alix is a bona fide exosomal regulator and skeletal muscle cells can release Alix-positive nano-sized extracellular vesicles, offering a new paradigm for understanding how myofibers communicate within skeletal muscle and with other organs. S-palmitoylation is a reversible lipid post-translational modification, involved in different biological processes, such as the trafficking of membrane proteins, achievement of stable protein conformations, and stabilization…
A 300 IR sublingual tablet is an effective, safe treatment for house dust mite-induced allergic rhinitis: An international, double-blind, placebo-con…
2021
Background: Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies. Objective: We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus:Dermatophagoides farinae 1:1 extract in adolescents (aged >_12) and adults with moderate to severe HDM-induced allergic rhinitis. Methods: In a phase III, international, double-blind, placebo controlled, rando…
Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers.
2018
Lipid peroxidation plays an important role in Alzheimer Disease, so corresponding metabolites found in urine samples could be potential biomarkers. The aim of this work is to develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry analytical method to determine a new set of lipid peroxidation compounds in urine samples. Excellent sensitivity was achieved with limits of detection between 0.08 and 17 nmol L-1, which renders this method suitable to monitor analytes concentrations in real samples. The method's precision was satisfactory with coefficients of variation around 5-17% (infra-day) and 8-19% (inter-day). The accuracy of the method was assessed by analysis o…
Tenofovir-induced toxicity in renal proximal tubular epithelial cells
2017
OBJECTIVE In-vivo studies suggest that mitochondria is involved in tenofovir (TFV)-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of TFV and its prodrug, TFV disoproxil fumarate, on mitochondrial function and cell survival/viability in a renal proximal tubular cell line. DESIGN AND METHODS We evaluated parameters of cellular proliferation/survival (cell count, cell cycle, viability) and mitochondrial function (oxygen consumption, mitochondrial membrane potential, reactive oxygen species production) in NRK-52E cells. Intracellular TFV was measured by HPLC and expression of antioxidant genes was analysed by real-…
DNA demethylation caused By 5-Aza-2'-Deoxycytidine induces mitotic alterations and aneuploidy
2016
Aneuploidy, the unbalanced number of chromosomes in a cell, is considered a prevalent form of genetic instability and is largely acknowledged as a condition implicated in tumorigenesis. Epigenetic alterations like DNA hypomethylation have been correlated with cancer initiation/progression. Furthermore, a growing body of evidence suggests the involvement of epigenome-wide disruption as a cause of global DNA hypomethylation in aneuploidy generation. Here, we report that the DNA hypomethylating drug 5-aza-2′-deoxycytidine (DAC), affects the correct ploidy of nearly diploid HCT-116 human cells by altering the methylation pattern of the chromosomes. Specifically, we show that a DAC-induced reduc…
Zinc oxide nanoparticles mediated cytotoxicity, mitochondrial membrane potential and level of antioxidants in presence of melatonin.
2017
Zinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products and are currently being investigated for biomedical applications. However, they have the potential to interact with macromolecules like proteins, lipids and DNA within the cells which makes the safe biomedical application difficult. The toxicity of the ZnO NP is mainly attributed reactive oxygen species (ROS) generation. Different strategies like iron doping, polymer coating and external supply of antioxidants have been evaluated to minimize the toxic potential of ZnO NPs. Melatonin is a hormone secreted by the pineal gland with great antioxidant properties. The melatonin is known to protect cells from ROS inducing …
Physiological Levels of Nitric Oxide Diminish Mitochondrial Superoxide. Potential Role of Mitochondrial Dinitrosyl Iron Complexes and Nitrosothiols.
2017
Mitochondria are the major source of superoxide radicals and superoxide overproduction contributes to cardiovascular diseases and metabolic disorders. Endothelial dysfunction and diminished nitric oxide levels are early steps in the development of these pathological conditions. It is known that physiological production of nitric oxide reduces oxidative stress and inflammation, however, the precise mechanism of “antioxidant” effect of nitric oxide is not clear. In this work we tested the hypothesis that physiological levels of nitric oxide diminish mitochondrial superoxide production without inhibition of mitochondrial respiration. In order to test this hypothesis we analyzed effect of low p…
Peripheral artery disease, redox signaling, oxidative stress – Basic and clinical aspects
2017
Reactive oxygen and nitrogen species (ROS and RNS, e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage). It is well known that redox biology and oxidative stress play an important role in this setting. We here discuss the major pathways of oxidative stress and re…