Project description:Basophils have emerged in recent years as a small but potent subpopulation of leukocytes capable of bridging innate and adaptive immunity. They can be activated through IgE-dependent and IgE-independent mechanisms to release preformed mediators and to produce Th2 cytokines. In addition to their role in protective immunity to helminths, basophils are major participants in allergic reactions as diverse as anaphylaxis and immediate hypersensitivity reactions, late-phase hypersensitivity reactions, and delayed hypersensitivity reactions. Additionally, basophils have been implicated in the pathophysiology of autoimmune diseases such as lupus nephritis and rheumatoid arthritis, and the modulation of immune responses to bacterial infections, as well as being a feature of myelogenous leukemias. Distinct signals for activation, degranulation, transendothelial migration, and immune regulation are being defined, and demonstrate the important role of basophils in promoting a Th2 microenvironment. These mechanistic insights are driving innovative approaches for diagnostic testing and therapeutic targeting of basophils.
Project description:In this Special Issue of Nutrients, "The Role of Selenium in Health and Disease" covers diverse diseases in the 8 original research articles and 2 reviews, such as cardiovascular disorders (CVD), metabolic syndrome, obesity, cancer, and viral infection, and highlights novel potential biomarkers of disease risk and prognosis [...].
Project description:Among all the NAD+ precursors, nicotinamide riboside (NR) has gained the most attention as a potent NAD+-enhancement agent. This recently discovered vitamin, B3, has demonstrated excellent safety and efficacy profiles and is orally bioavailable in humans. Boosting intracellular NAD+ concentrations using NR has been shown to provide protective effects against a broad spectrum of pathological conditions, such as neurodegenerative diseases, diabetes, and hearing loss. In this review, an integrated overview of NR research will be presented. The role NR plays in the NAD+ biosynthetic pathway will be introduced, followed by a discussion on the synthesis of NR using chemical and enzymatic approaches. NR's effects on regulating normal physiology and pathophysiology will also be presented, focusing on the studies published in the last five years.
Project description:Precision medicine is an integrative approach to cardiovascular disease prevention and treatment that considers an individual's genetics, lifestyle, and exposures as determinants of their cardiovascular health and disease phenotypes. This focus overcomes the limitations of reductionism in medicine, which presumes that all patients with the same signs of disease share a common pathophenotype and, therefore, should be treated similarly. Precision medicine incorporates standard clinical and health record data with advanced panomics (ie, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics) for deep phenotyping. These phenotypic data can then be analyzed within the framework of molecular interaction (interactome) networks to uncover previously unrecognized disease phenotypes and relationships between diseases, and to select pharmacotherapeutics or identify potential protein-drug or drug-drug interactions. In this review, we discuss the current spectrum of cardiovascular health and disease, population averages and the response of extreme phenotypes to interventions, and population-based versus high-risk treatment strategies as a pretext to understanding a precision medicine approach to cardiovascular disease prevention and therapeutic interventions. We also consider the search for resilience and Mendelian disease genes and argue against the theory of a single causal gene/gene product as a mediator of the cardiovascular disease phenotype, as well as an Erlichian magic bullet to solve cardiovascular disease. Finally, we detail the importance of deep phenotyping and interactome networks and the use of this information for rational polypharmacy. These topics highlight the urgent need for precise phenotyping to advance precision medicine as a strategy to improve cardiovascular health and prevent disease.
Project description:Cellular senescence is a state of irreversible cell cycle arrest in response to an array of cellular stresses. An important role for senescence has been shown for a number of pathophysiological conditions that include cardiovascular disease, pulmonary fibrosis, and diseases of the skin. However, whether senescence contributes to the progression of age-related macular degeneration (AMD) has not been studied in detail so far and the present review describes the recent research on this topic. We present an overview of the types of senescence, pathways of senescence, senescence-associated secretory phenotype (SASP), the role of mitochondria, and their functional implications along with antisenescent therapies. As a central mechanism, senescent cells can impact the surrounding tissue microenvironment via the secretion of a pool of bioactive molecules, termed the SASP. An updated summary of a number of new members of the ever-growing SASP family is presented. Further, we introduce the significance of mechanisms by which mitochondria may participate in the development of cellular senescence. Emerging evidence shows that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment. Based on recent studies, there is reasonable evidence that senescence could be a modifiable factor, and hence, it may be possible to delay age-related diseases by modulating basic aging mechanisms using SASP inhibitors/senolytic drugs. Thus, antisenescent therapies in aging and age-related diseases appear to have a promising potential.
Project description:Parkinson's disease (PD), the main risk factor of which is age, is one of the most common neurodegenerative diseases, thus presenting a substantial burden on the health of affected individuals as well as an economic burden. Sirtuin 2 (SIRT2), a subtype in the family of sirtuins, belongs to class III histone deacetylases (HDACs). It is known that SIRT2 levels increase with aging, and a growing body of evidence has been accumulating, showing that the activity of SIRT2 mediates various processes involved in PD pathogenesis, including aggregation of α-synuclein (α-syn), microtubule function, oxidative stress, inflammation, and autophagy. There have been conflicting reports about the role of SIRT2 in PD, in that some studies indicate its potential to induce the death of dopaminergic (DA) neurons, and that inhibition of SIRT2 may, therefore, have protective effects in PD. Other studies suggest a protective role of SIRT2 in the context of neuronal damage. As current treatments for PD are directed at alleviating symptoms and are very limited, a comprehensive understanding of the enzymology of SIRT2 in PD may be essential for developing novel therapeutic agents for the treatment of this disease. This review article will provide an update on our knowledge of the structure, distribution, and biological characteristics of SIRT2, and highlight its role in the pathogenesis of PD.
Project description:Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. It is now clear that genetic susceptibility and environmental factors play a role in disease etiology and progression. Because environmental factors are involved with the majority of the cases of PD, it is important to understand the role nutrition plays in both neuroprotection and neurodegeneration. Recent epidemiological studies have revealed the promise of some nutrients in reducing the risk of PD. In contrast, other nutrients may be involved with the etiology of neurodegeneration or exacerbate disease progression. This review summarizes the studies that have addressed these issues and describes in detail the nutrients and their putative mechanisms of action in PD.
Project description:Enlargement of the vestibular aqueduct (EVA) is a common inner ear malformation found in children with sensorineural hearing loss that is frequently associated with loss-of-function or hypo-function mutations of SLC26A4. SLC26A4 codes for pendrin, which is a protein that is expressed in apical membranes of selected epithelia and functions as an anion exchanger. The comparatively high prevalence of EVA provides a strong imperative to develop rational interventions that delay, ameliorate or prevent hearing loss associated with this phenotype. The development of rational interventions requires a fundamental understanding of the role that pendrin plays in the normal development of hearing, as well as a detailed understanding of the pathobiologic mechanisms that, in the absence of fully functional pendrin, lead to an unstable hearing phenotype, with fluctuating or progressive loss of hearing. This review summarizes studies in mouse models that have focused on delineating the role of pendrin in the physiology of the inner ear and the pathobiology that leads to hearing loss.
Project description:Dysregulation of long noncoding RNA (lncRNA) expression is linked to the development of various diseases. Recently, an emerging body of evidence has indicated that lncRNAs play important roles in the pathogenesis of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative Colitis (UC). In IBD, lncRNAs have been shown to be involved in diverse processes, including the regulation of intestinal epithelial cell apoptosis, association with lipid metabolism, and cell-cell interactions, thereby enhancing inflammation and the functional regulation of regulatory T cells. In this review, we aim to summarize the current knowledge regarding the role of lncRNAs in IBD and highlight potential avenues for future investigation. We also collate potentially immune-relevant, IBD-associated lncRNAs identified through a built-by association analysis with respect to their neighboring protein-coding genes within IBD-susceptible loci. We further underscore their importance by highlighting their enrichment for various aspects of immune system regulation, including antigen processing/presentation, immune cell proliferation and differentiation, and chronic inflammatory responses. Finally, we summarize the potential of lncRNAs as diagnostic biomarkers in IBD.
Project description:Huntington's disease (HD) is a neurodegenerative disease characterized by several symptoms encompassing movement, cognition, and behavior. The mutation of the IT15 gene encoding for the huntingtin protein is the cause of HD. Mutant huntingtin interacts with and impairs the function of several transcription factors involved in neuronal survival. Although many mechanisms determining neuronal death have been described over the years, the significant role of inflammation has gained momentum in the last decade. Drugs targeting the elements that orchestrate inflammation have been considered powerful tools to treat HD. In this review, we will describe the data supporting inflammasome and NLRP3 as a target of therapeutics to fight HD, deepening the possible mechanisms of action underlying these effects.