ABSTRACT
miRNA expression profile and predicted pathways involved in selected limb-girdle muscular dystrophy (LGMD)2A/2B patients were investigated. A total of 187 miRNAs were dysregulated in all patients, with six miRNAs showing opposite regulation in LGMD2A versus LGMD2B patients. Silico analysis evidence: (1) a cluster of the dysregulated miRNAs resulted primarily involved in inflammation and calcium metabolism, and (2) two genes predicted as controlled by calcium-assigned miRNAs (Vitamin D Receptor gene and Guanine Nucleotide Binding protein beta polypeptide 1gene) showed an evident upregulation in LGMD2B patients, in accordance with miRNA levels. Our data support alterations in calcium pathway status in LGMD 2A/B, suggesting myofibre calcium imbalance as a potential therapeutic target. Copyright © 2016 John Wiley & Sons, Ltd.
Subject(s)
Calcium/metabolism , Gene Expression Profiling , MicroRNAs/genetics , Muscular Dystrophies, Limb-Girdle/genetics , Receptors, Calcitriol/genetics , Signal Transduction/genetics , Adolescent , Adult , Child , Child, Preschool , Female , GTP-Binding Protein beta Subunits/genetics , GTP-Binding Protein beta Subunits/metabolism , Gene Expression Regulation , Humans , Male , MicroRNAs/metabolism , Middle Aged , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Receptors, Calcitriol/metabolismABSTRACT
Toll-like receptors (TLR) are important innate immune proteins for the identification and clearance of invading pathogen. TLR signal through adaptor proteins, most commonly myeloid differentiation primary response gene 88 (MyD88). Inappropriate response of specific TLR has been implicated in certain autoimmune diseases, such as multiple sclerosis (MS). Activation of TLR2, TLR4, TLR7 and TLR9 plays a role in experimental allergic encephalomyelitis (EAE), a murine model of MS, while TLR3 activation protects from disease. Therefore, TLR-modulation could be an important adjuvant to current treatments. Here, we focus on TLR involved in EAE and MS pathogenesis highlighting specific components targeting TLR that might offer further therapeutic possibilities.
Subject(s)
Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trends , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Signal Transduction/immunology , Toll-Like Receptors/metabolism , Animals , Complementary Therapies/methods , Complementary Therapies/trends , Disease Models, Animal , Humans , Multiple Sclerosis/pathology , Signal Transduction/drug effects , Toll-Like Receptors/agonists , Toll-Like Receptors/physiologyABSTRACT
We calculate the first-passage time distribution for diffusion through a cylindrical pore with sticky walls. A particle diffusively explores the interior of the pore through a series of binding and unbinding events with the cylinder wall. Through a diagrammatic expansion we obtain first-passage time statistics for the particle's exit from the pore. Connections between the model and nucleocytoplasmic transport in cells are discussed.
