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Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology
2020
Bone remodeling is uncoupled in the multiple myeloma (MM) bone marrow niche, resulting in enhanced osteoclastogenesis responsible of MM-related bone disease (MMBD). Several studies have disclosed the mechanisms underlying increased osteoclast formation and activity triggered by the various cellular components of the MM bone marrow microenvironment, leading to the identification of novel targets for therapeutic intervention. In this regard, recent attention has been given to non-coding RNA (ncRNA) molecules, that finely tune gene expression programs involved in bone homeostasis both in physiological and pathological settings. In this review, we will analyze major signaling pathways involved …
Methods for RNA Modification Mapping Using Deep Sequencing: Established and New Emerging Technologies
2019
New analytics of post-transcriptional RNA modifications have paved the way for a tremendous upswing of the biological and biomedical research in this field. This especially applies to methods that included RNA-Seq techniques, and which typically result in what is termed global scale modification mapping. In this process, positions inside a cell`s transcriptome are receiving a status of potential modification sites (so called modification calling), typically based on a score of some kind that issues from the particular method applied. The resulting data are thought to represent information that goes beyond what is contained in typical transcriptome data, and hence the field has taken to use …
RNA Modifications Modulate Activation of Innate Toll-Like Receptors
2019
Self/foreign discrimination by the innate immune system depends on receptors that identify molecular patterns as associated to pathogens. Among others, this group includes endosomal Toll-like receptors, among which Toll-like receptors (TLR) 3, 7, 8, and 13 recognize and discriminate mammalian from microbial, potentially pathogen-associated, RNA. One of the discriminatory principles is the recognition of endogenous RNA modifications. Previous work has identified a couple of RNA modifications that impede activation of TLR signaling when incorporated in synthetic RNA molecules. Of note, work that is more recent has now shown that RNA modifications in their naturally occurring context can have …
Epigenetic Regulation in the Pathogenesis of Sjögren Syndrome and Rheumatoid Arthritis
2019
Autoimmune rheumatic diseases, such as Sjögren syndrome (SS) and rheumatoid arthritis (RA), are characterized by chronic inflammation and autoimmunity, which cause joint tissue damage and destruction by triggering reduced mobility and debilitation in patients with these diseases. Initiation and maintenance of chronic inflammatory stages account for several mechanisms that involve immune cells as key players and the interaction of the immune cells with other tissues. Indeed, the overlapping of certain clinical and serologic manifestations between SS and RA may indicate that numerous immunologic-related mechanisms are involved in the physiopathology of both these diseases. It is widely accept…
Environmental epigenetics in zebrafish
2017
Abstract It is widely accepted that the epigenome can act as the link between environmental cues, both external and internal, to the organism and phenotype by converting the environmental stimuli to phenotypic responses through changes in gene transcription outcomes. Environmental stress endured by individual organisms can also enforce epigenetic variations in offspring that had never experienced it directly, which is termed transgenerational inheritance. To date, research in the environmental epigenetics discipline has used a wide range of both model and non-model organisms to elucidate the various epigenetic mechanisms underlying the adaptive response to environmental stimuli. In this rev…
H1.0 Linker Histone as an Epigenetic Regulator of Cell Proliferation and Differentiation
2018
H1 linker histones are a class of DNA-binding proteins involved in the formation of supra-nucleosomal chromatin higher order structures. Eleven non-allelic subtypes of H1 are known in mammals, seven of which are expressed in somatic cells, while four are germ cell-specific. Besides having a general structural role, H1 histones also have additional epigenetic functions related to DNA replication and repair, genome stability, and gene-specific expression regulation. Synthesis of the H1 subtypes is differentially regulated both in development and adult cells, thus suggesting that each protein has a more or less specific function. The somatic variant H1.0 is a linker histone that was recognized…
Extracellular Vesicle‐Associated RNA as a Carrier of Epigenetic Information
2017
Post-transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis-acting signals (zip codes), usually present in their 5'- and 3'-untranslated regions (UTRs). By binding to these signals, trans-acting factors, such as RNA-binding proteins (RBPs), and/or non-coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non-coding RNAs of different sizes. The release of extracellular vesicles (EVs) is a conserved process that allows both normal and cancer cells to horizontally tran…
Ketogenic diet and microbiota: Friends or enemies?
2019
Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight …
Tailoring the Interface of Biomaterials to Design Effective Scaffolds
2018
Tissue engineering (TE) is a multidisciplinary science, which including principles from material science, biology and medicine aims to develop biological substitutes to restore damaged tissues and organs. A major challenge in TE is the choice of suitable biomaterial to fabricate a scaffold that mimics native extracellular matrix guiding resident stem cells to regenerate the functional tissue. Ideally, the biomaterial should be tailored in order that the final scaffold would be (i) biodegradable to be gradually replaced by regenerating new tissue, (ii) mechanically similar to the tissue to regenerate, (iii) porous to allow cell growth as nutrient, oxygen and waste transport and (iv) bioactiv…
CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges.
2020
During the past decades, several therapeutic approaches have been developed and made rapidly available for many patients afflicted with lysosomal storage disorders (LSDs), inborn organelle disorders with broad clinical manifestations secondary to the progressive accumulation of undegraded macromolecules within lysosomes. These conditions are individually rare, but, collectively, their incidence ranges from 1 in 2,315 to 7,700 live-births. Most LSDs are manifested by neurological symptoms or signs, including developmental delay, seizures, acroparesthesia, motor weakness, and extrapyramidal signs. The chronic and later-onset clinical forms are at one end of the continuum spectrum and are char…