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Regulation of Inflammation; Its Resolution and Therapeutic Targeting

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453597 Year: Pages: 105 DOI: 10.3389/978-2-88945-359-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-02-27 16:16:45
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Inflammation is a fundamental protective mechanism and at the same time the driving force of a variety of major diseases in humans. Indeed, acute self-resolving inflammation usually plays a positive role for the host, as exemplified by infectious diseases where its positive role is well established and testified by its perception as innate immunity. On the other hand, non-resolving inflammation and consequent chronicization is a key determinant of immunopathology and clinical manifestations of most major diseases in humans. As a consequence, it is increasing appreciated that the problem with inflammation is not how often it starts, but how often it fails to resolve. Appropriate resolution of inflammatory responses, which also drives activation of tissue damage repair mechanisms and return of local tissues to homeostasis, is a necessary process for ongoing health. Interestingly, cells sustaining these processes are also key to the proinflammatory responses, and the underlying “pro-resolving” molecular pathways are triggered as part of the pro-inflammatory response. This clearly indicates resolution of inflammation as an active process requiring functional repolarization of inflammatory cells that calls our attention on the underlying molecular mechanisms. The increasing number of anti-inflammatory drugs best-sellers in the pharma market is a clear indication of the relevance of having inflammation under check; nonetheless, there is still a great need for better acting pharmacological tools for the control of inflammation. Indeed, the remarkable success of biological drugs targeting proinflammatory cytokines has indicates that tools able to block proinflammatory mediators have promising applications, but at the same time has made clear that there are intrinsic limitations to this approach which frequently vanish undermine the activity of single targeting drugs, including the well-known redundancy of inflammatory mediators. Under self-limiting conditions inflammation spontaneously resolves in an active process. Some cellular and molecular mechanisms involved in inflammation resolution have been uncovered in the recent past, and include generation of specific cytokines, apoptosis of inflammatory leukocytes, lipid mediators, macrophage repolarization and others are likely to be revealed in the next future, since loss-of-function mutations of an increasing number of genes results in the development of spontaneous inflammation in experimental animals. We argue that “pushing for“ inflammation resolution by exploiting active naturally-occurring pro-resolving processes may have significant advantages over the attempt to simply “push back” inflammation by passive blockade of proinflammatory mediators. At present the research in the field of inflammation aims at identifying and validates new molecules involved in the resolution of inflammation as a basis for the development of innovative therapeutic strategies in chronic inflammatory and autoimmune diseases. This involves the discovery of new natural or synthetic “pro-resolving” molecules from plant and animals and the investigation of endogenous inflammation “pro-resolving” mechanisms, including atypical chemokine receptors, decoy receptors, and microRNA. An extensive effort is focused on the regulation by “pro-resolving” agents on two molecular systems of key relevance in inflammation: the chemokine system, which regulates recruitment, permanence and egress of leukocyte in tissues; and the Toll Like Receptor (TLR)/IL-1R system, which is central for the activation of infiltrating leukocytes.

Lyme Disease: Recent Advances and Perspectives

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195572 Year: Pages: 114 DOI: 10.3389/978-2-88919-557-2 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Internal medicine
Added to DOAB on : 2016-01-19 14:05:46
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The interplay between host and pathogen is a complex co-evolutionary battle of surveillance and evasion. The pathogen continuously develops mechanisms to subvert the immune response in order to establish infection while the immune system responds with novel mechanisms of detection. Because the majority of Lyme disease pathology is due to an over-exuberant immune response, much research in Borrelia burgdorferi pathogenesis has been devoted to understanding the mammalian host response to the bacterium. Immunological studies continue to be an active area of research employing emerging techniques, such as intra-vital imaging. These studies have furthered our understanding of inflammatory processes during long-term infection and provided some surprising insights, such as the continued presence of bacterial products after clearance. The field of Lyme disease has long debated the etiology of long-term inflammation and recent studies in the murine host have shed light on relevant cell types and inflammatory mediators that participate in the pathology of Lyme arthritis. Live imaging and bioluminescent studies have allowed for a novel view of the bacterial life cycle, including the tick mid-gut, tick-to-mammal transmission and dissemination throughout a mouse. A number of tick and bacterial proteins have been shown to participate in the completion of the enzootic cycle. Novel mechanisms of gene regulation are continuously being identified. However, B. burgdorferi lacks many traditional virulence factors, such as toxins or specialized secretion systems. Many genes in the B. burgdorferi genome have no known homolog in other bacteria. Therefore, studies focusing on host-pathogen interactions have therefore been limited by an incomplete understanding of the repertoire of bacterial virulence factors. Questions such as how the pathogen causes disease, colonizes the tick and evades host immune-surveillance have been difficult to address. Genetic studies involving single gene deletions have identified a number of important bacterial proteins, but a large-scale genomics approach to identify virulence factors has not been attempted until recently. The generation of a site-directed mutagenesis library is an important step towards a detailed analysis of the B. burgdorferi genome and pathogenome. Using this library, high-throughput genomic studies, utilizing techniques such as massively parallel sequencing have been promising and could be used to identify novel virulence determinants of disease in the mammalian host or persistence in the tick vector. Continued research on this unique pathogen and its specific interaction with host and vector may have far reaching consequences and provide insights for diverse disciplines including ecology, infectious disease, and immunology. Here, several reviews will discuss the most recent advances and future studies to be undertaken in the field of B. burgdorferi biology.

The Interplay of Microbiome and Immune Response in Health and Diseases

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ISBN: 9783039216468 9783039216475 Year: Pages: 206 DOI: 10.3390/books978-3-03921-647-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2019-12-09 11:49:16
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[Increasing evidence suggests that microbiota and especially the gut microbiota (the microbes inhabiting the gut including bacteria, archaea, viruses, and fungi) plays a key role in human physiology and pathology. Recent findings indicate how dysbiosis—an imbalance in the composition and organization of microbial populations—could severely impact the development of different medical conditions (from metabolic to mood disorders), providing new insights into the comprehension of diverse diseases, such as IBD, obesity, asthma, autism, stroke, diabetes, and cancer. Given that microbial cells in the gut outnumber host cells, microbiota influences human physiology both functionally and structurally. Microbial metabolites bridge various—even distant—areas of the organism by way of the immune and hormone system. For instance, it is now clear that the mutual interaction between the gastrointestinal tract and the brain (gut–brain axis), often involves gut microbiota, indicating that the crosstalk between the organism and its microbial residents represents a fundamental aspect of both the establishment and maintenance of healthy conditions. Moreover, it is crucial to recognize that beyond the intestinal tract, microbiota populates other host organs and tissues (e.g., skin and oral mucosa). We have edited this eBook with the aim of publishing manuscripts focusing on the impact of microbiota in the development of different diseases and their associated treatments.]

Keywords

microbiota --- rheumatoid arthritis --- anti-TNF-? --- methotrexate --- etanercept --- disease activity --- microbiome --- health --- precision medicine --- genomics --- bacteriocins --- bacteriophages --- antibiotics --- gastrointestinal diseases --- dysbiosis --- gut barrier --- gut microbiota --- virus --- vaginal microbiota --- HIV --- HPV --- HSV2 --- cytokines --- chemokines --- innate immunity --- adaptive immunity --- microbiota --- autoimmunity --- etiopathogenesis --- Candida albicans --- 2,3-dihydroxy-4-methoxyBenzaldehyde --- melanin --- colitis --- anaerobic bacteria --- aerobic bacteria --- gut microbiota --- gut-liver axis --- chronic liver diseases --- fecal transplantation --- probiotics --- gut microbiota --- immunological niche --- dysbiosis --- cancer --- immune system --- cutaneous immunity --- microbiome --- Staphylococcus spp., T cells --- Staphylococcus aureus --- Staphylococcus epidermis --- commensals --- atopic dermatitis --- intravenous immunoglobulin G --- colitis --- dextran sulfate sodium --- mice --- inflammation --- cytokines --- Candida albicans --- Escherichia coli --- Enterococcus faecalis --- gut microbiota --- chemo free treatment --- lymphoid malignancies --- 16S rRNA gene --- chondroitin sulfate disaccharide --- co-occurrence network --- global network --- microbial interactions --- microbiome --- modularity --- superoxide dismutase --- gut microbiota --- macrophages --- TLR mimicry --- immune epigenetics --- metabolism --- sterile inflammation --- microbiota --- microbiome --- immunotherapy --- adoptive cell transfer (ACT) --- CAR T-cell --- TCR --- TIL --- checkpoint inhibitors --- immuno-oncology --- cancer --- diet --- n/a

Dual Specificity Phosphatases: From Molecular Mechanisms to Biological Function

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ISBN: 9783039216888 9783039216895 Year: Pages: 240 DOI: 10.3390/books978-3-03921-689-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:16
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Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of protein tyrosine phosphatases with the ability to dephosphorylate Ser/Thr and Tyr residues from proteins, as well as from other non-proteinaceous substrates including signaling lipids. DUSPs include, among others, MAP kinase (MAPK) phosphatases (MKPs) and small-size atypical DUSPs. MKPs are enzymes specialized in regulating the activity and subcellular location of MAPKs, whereas the function of small-size atypical DUSPs seems to be more diverse. DUSPs have emerged as key players in the regulation of cell growth, differentiation, stress response, and apoptosis. DUSPs regulate essential physiological processes, including immunity, neurobiology and metabolic homeostasis, and have been implicated in tumorigenesis, pathological inflammation and metabolic disorders. Accordingly, alterations in the expression or function of MKPs and small-size atypical DUSPs have consequences essential to human disease, making these enzymes potential biological markers and therapeutic targets. This Special Issue covers recent advances in the molecular mechanisms and biological functions of MKPs and small-size atypical DUSPs, and their relevance in human disease.

Virus Bioinformatics

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ISBN: 9783039218820 9783039218837 Year: Pages: 330 DOI: 10.3390/books978-3-03921-883-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2020-04-07 23:07:08
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Virus bioinformatics is evolving and succeeding as an area of research in its own right, representing the interface of virology and computer science. Bioinformatic approaches to investigate viral infections and outbreaks have become central to virology research, and have been successfully used to detect, control, and treat infections of humans and animals. As part of the Third Annual Meeting of the European Virus Bioinformatics Center (EVBC), we have published this Special Issue on Virus Bioinformatics.

Keywords

bioinformatics --- virus --- comparative genomics --- software --- Base-By-Base --- BBB --- poxvirus --- ASFV --- MSA --- foot-and-mouth disease virus (FMDV) --- bovine soft palate --- nasopharynx --- transcriptomics --- proteomics --- bioinformatics --- virus-host interaction --- innate immune system --- interferon-stimulated genes (ISG) --- cellular immunity --- codon frequency distribution --- HPV58 --- minor capsid protein --- TLR agonist --- prophylaxis --- virus --- infection --- fluorescent reporter protein --- image quantification --- Hepatitis C virus --- Yellow Fever Virus --- polyomavirus --- Coxsackievirus B4 --- bivalve --- virome --- RNA-seq --- RNA viruses --- sncRNA --- ADAR --- RNAi --- Marek’s disease virus (MDV) --- RNA-seq --- transcriptome --- splicing --- polycistronic viral transcripts --- primary B cells --- RB1B --- CVI988/Rispens --- ICP0 --- DNA replication --- ori --- mitochondria --- Rickettsia --- gram-positive bacteria --- APMV --- Mimivirus --- giant virus --- eukaryogenesis --- flavivirus --- non-coding RNA --- secondary structure --- endogenous viral elements --- bioinformatics --- horizontal gene transfer --- virus-to-host gene transfer --- HMM --- tobacco mosaic virus --- Drosophila --- capsid protein --- deep sequencing --- virus genomics --- hepatitis C virus --- variant calling --- sequence interpretation --- drug resistance --- bioinformatics --- alignment --- assembly --- taxonomic classification --- time series --- data transformation --- DWT --- DFT --- PAA --- data compression --- compressive genomics --- RNAseq --- honey bees --- deformed wing virus --- quasispecies --- apiary pests --- recombination --- mRNA structure --- structure database --- secondary structure --- viral mRNA --- subVOG --- structurally related --- RNA structure --- structurally homogenous --- structurally related --- mRNA families --- Amebae viruses --- viral evolution --- protein domains --- mimivirus --- dsdna viruses --- translation machinery --- pandoravirus --- NCLDV --- virology --- virus bioinformatics --- software --- systems virology --- metagenomics --- virome --- viral taxonomy --- virus classification --- genome evolution --- bacteriophage --- virosphere --- chemical organization theory --- influenza A --- virus dynamics modeling --- complex networks analysis --- viral metagenome --- groundwater --- aquifer --- AquaDiva --- sequencing library preparation --- virus proteomics --- mass spectrometry --- virus diagnostics --- data analysis --- targeted proteomics --- peptide selection --- parallel reaction monitoring

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