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The Coevolution of IDO1 and AhR in the Emergence of Regulatory T Cells in Mammals

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197293 Year: Pages: 89 DOI: 10.3389/978-2-88919-729-3 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Abstract

Indoleamine 2,3-dioxygenase (IDO1) is an ancestral enzyme that, initially confined to the regulation of tryptophan availability in local tissue microenvironments, is now considered to play a wider role that extends to homeostasis and plasticity of the immune system. Thus IDO biology has implications for many aspects of immunopathology, including viral infections, neoplasia, autoimmunity, and chronic inflammation. Its immunoregulatory effects are mainly mediated by dendritic cells (DCs) and involve not only tryptophan deprivation but also production of kynurenines that act on IDO- DCs, thus rendering an otherwise stimulatory DC capable of regulatory effects, as well as on T cells. The aryl hydrocarbon receptor (AhR) is a ligand-operated transcription factor originally recognized as the effector mediating the pathologic effects of dioxins and other pollutants. However, it is now well established that AhR activation by endogenous ligands can produce immunoregulatory effects. The IDO1 mechanism appears to have been selected through phylogenesis primarily to prevent overreacting responses to TLR-recognized pathogen-associated molecular patterns, and only later did it become involved in the response to T cell receptor-recognized antigens. As a result, in mammals, IDO1 has become pivotal in fetomaternal tolerance, at a time when regulatory T cells emerged to meet the same need, namely protecting the fetus. IDO1 and regulatory T (Treg) cells may have then coevolved to broaden their function well beyond their initial task of protecting the fetus, such that, in acquired immunity, IDO1 (with its dual enzymic and signaling function) has turned into an important component of the peripheral generation and effector function of regulatory T cells. AhR, in turn, which has a role in regulatory T-cell generation, is presumed to have evolved from invertebrates, where it served a ligand-independent role in normal development processes. Evolution of the receptor in vertebrates resulted in the ability to bind structurally different ligands, including xenobiotics and microbiota-derived catabolites. Considering the inability of invertebrate AhR homologs to bind dioxins, the adaptive role of the AhR to act as a regulator of xenobiotic-metabolizing enzymes may have been a vertebrate innovation, to later acquire an additional immune regulatory role by coevolutive pressure in mammals by IDO1 and regulatory T cells. Thus an entirely new paradigm in immunology, and more specifically in immune tolerance, is the coevolution of three systems, namely, the IDO1 mechanism, AhR-driven gene transcription, and T-cell regulatory activity, that originating from the initial need of protecting the fetus in mammals, have later turned into a pivotal mechanism of peripheral tolerance in autoimmunity, transplantation, and neoplasia.

Hormones, Metabolism and the Benefits of Exercise

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Book Series: Research and Perspectives in Endocrine Interactions ISSN: 1861-2253 ISBN: 9783319727899 9783319727905 Year: Pages: 102 DOI: https://doi.org/10.1007/978-3-319-72790-5 Language: English
Publisher: Springer Nature Grant: Fondation Ipsen
Subject: Internal medicine
Added to DOAB on : 2018-06-29 10:36:57
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The world is faced with an epidemic of metabolic diseases such as obesity and type 2 diabetes. This is due to changes in dietary habits and the decrease in physical activity. Exercise is usually part of the prescription, the first line of defense, to prevent or treat metabolic disorders. However, we are still learning how and why exercise provides metabolic benefits in human health. This open access volume focuses on the cellular and molecular pathways that link exercise, muscle biology, hormones and metabolism. This will include novel “myokines” that might act as new therapeutic agents in the future.

Biomedical Insights that Inform the Diagnosis of ME/CFS

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ISBN: 9783039283903 9783039283910 Year: Pages: 202 DOI: 10.3390/books978-3-03928-391-0 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics --- Medicine (General)
Added to DOAB on : 2020-04-07 23:07:09
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic health condition that is often misunderstood or ignored by health establishments. The lack of definitive diagnostic markers to separate ME/CFS patients from the healthy population as well as from other chronic disorders is problematic for both health professionals and researchers. A consortium of Australian researchers gathered to systematically understand ME/CFS, ranging from a deep analysis of clinical and pathology data to metabolomic profiles and the investigation of mitochondrial function. From this broad collaboration, a number of compelling insights have arisen that may form the basis of specific serum, blood, and/or urinary biomarkers of ME/CFS. This Special Edition reports on a conference centred on these biomedical discoveries, with other contributions, with a translation focus for predictive markers for ME/CFS diagnosis. By supporting health professionals with developments in diagnostics for this condition, the patients and their families will hopefully benefit from an improved recognition of the biomedical underpinnings of the condition and will be better able to access the care that is urgently required. This Special Edition contains a mix of speaker submissions and other accepted manuscripts that contributed to our objective of advancing biomedical insights to enable the accurate diagnosis of ME/CFS.

Keywords

myalgic encephalomyelitis --- chronic fatigue syndrome --- diagnosis --- symptoms --- muscles --- neurology --- myalgic encephalomyelitis --- chronic fatigue syndrome --- post-exertional malaise --- assessment --- patient-driven questionnaire --- participatory research --- myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) --- energy metabolism --- potential biomarkers --- fatigue syndrome --- chronic --- exercise --- hypoacetylation --- methylhistidine --- histone deacetylation --- myalgic encephalomyelitis --- chronic fatigue syndrome --- diagnostic biomarker --- inflammation and immunity --- metabolism --- mitochondria --- circadian rhythm --- neuro-inflammation --- myalgic encephalomyelitis --- chronic fatigue syndrome --- activin --- pathology --- biomarker --- cytokine --- machine learning --- reference intervals --- myalgic encephalomyelitis --- chronic fatigue syndrome --- ME/CFS --- diagnosis --- metabolism --- mitochondria --- inflammation --- immune system --- signaling --- gut microbiota --- tryptophan metabolism --- indoleamine-2,3-dioxygenase --- bistability --- kynurenine pathway --- substrate inhibition --- myalgic encephalomyelitis --- chronic fatigue syndrome --- mathematical model --- critical point --- immunological --- chronic fatigue syndrome --- myalgic encephalomyelitis --- biomarker --- neuroimmune --- Epstein Barr virus --- hypothalamic–pituitary–adrenal axis --- CFS (Chronic Fatigue Syndrome) --- ME (Myalgic Encephalomyelitis) --- medical retirement --- prognosis --- work rehabilitation --- n/a

Biological Crystallization

Authors: --- ---
ISBN: 9783039214037 9783039214044 Year: Pages: 184 DOI: 10.3390/books978-3-03921-404-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
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For at least six hundred million years, life has been a fascinating laboratory of crystallization, referred to as biomineralization. During this huge lapse of time, many organisms from diverse phyla have developed the capability to precipitate various types of minerals, exploring distinctive pathways for building sophisticated structural architectures for different purposes. The Darwinian exploration was performed by trial and error, but the success in terms of complexity and efficiency is evident. Understanding the strategies that those organisms employ for regulating the nucleation, growth, and assembly of nanocrystals to build these sophisticated devices is an intellectual challenge and a source of inspiration in fields as diverse as materials science, nanotechnology, and biomedicine. However, “Biological Crystallization” is a broader topic that includes biomineralization, but also the laboratory crystallization of biological compounds such as macromolecules, carbohydrates, or lipids, and the synthesis and fabrication of biomimetic materials by different routes. This Special Issue collects 15 contributions ranging from biological and biomimetic crystallization of calcium carbonate, calcium phosphate, and silica-carbonate self-assembled materials to the crystallization of biological macromolecules. Special attention has been paid to the fundamental phenomena of crystallization (nucleation and growth), and the applications of the crystals in biomedicine, environment, and materials science.

Keywords

polymyxin resistance --- colistin resistance --- MCR-1 --- protein crystal nucleation --- thermodynamic and energetic approach --- protein ‘affinity’ to water --- solubility --- balance between crystal bond energy and destructive surface energies --- supersaturation dependence of the crystal nucleus size --- ependymin (EPN) --- ependymin-related protein (EPDR) --- mammalian ependymin-related protein (MERP) --- Campylobacter consisus --- Crohn’s disease --- circular dichroism --- protein crystallization --- Csep1p --- protein crystallization --- biochemical aspects of the protein crystal nucleation --- classical and two-step crystal nucleation mechanisms --- bond selection during protein crystallization --- equilibration between crystal bond and destructive energies --- protein crystal nucleation in pores --- crystallization in solution flow --- crystallization --- microseed matrix screening --- seeding --- optimization --- human carbonic anhydrase IX --- neutron protein crystallography --- microbially induced calcite precipitation (MICP) --- heavy metals --- wastewater treatment --- bioprecipitation --- calcium carbonate --- drug discovery --- education --- crystallization --- crystallography --- nucleation --- micro-crystals --- agarose --- ferritin --- lysozyme --- proteinase k --- insulin --- calcium carbonate --- {00.1} calcite --- lithium ions --- ultrasonic irradiation --- vaterite transformation --- adsorption --- calcein --- crystal violet --- dyes --- diffusion --- H3O+ --- reductants --- color change --- gradients --- biomorphs --- barium carbonate --- silica --- PCDA --- pyrrole --- droplet array --- crystal growth --- calcium carbonate --- high-throughput --- biomimetic crystallization --- biomineralization --- polyacrylic acid --- Cry protein crystals --- metallothioneins --- bioremediation --- heavy metal contamination --- nanoapatites --- graphene --- crystallization --- nanocomposites --- lysozyme --- L-tryptophan --- N-acetyl-D-glucosamine --- chitosan --- MTT assay --- GTL-16 cells --- Haloalkane dehalogenase --- halide-binding site --- random microseeding --- biomineralization --- biomimetic materials --- biomorphs --- calcium carbonate --- nanoapatites --- nucleation --- growth --- crystallization of macromolecules --- bioremediation --- materials science --- biomedicine

Transmucosal Absorption Enhancers in the Drug Delivery Field

Authors: --- ---
ISBN: 9783039218486 9783039218493 Year: Pages: 406 DOI: 10.3390/books978-3-03921-849-3 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics --- Medicine (General)
Added to DOAB on : 2020-01-30 16:39:46
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Development of strategies to assist the movement of poorly permeable molecules across biological barriers has long been the goal of drug delivery science. In the last three decades, there has been an exponential increase in advanced drug delivery systems that aim to address this issue. However, most proprietary delivery technologies that have progressed to clinical development are based on permeation enhancers (PEs) that have a history of safe use in man. This Special Issue entitled “Transmucosal Absorption Enhancers in the Drug Delivery Field” aims to present the current state-of-the-art in the application of PEs to improve drug absorption. Emphasis is placed on identification of novel permeation enhancers, mechanisms of barrier alteration, physicochemical properties of PEs that contribute to optimal enhancement action, new delivery models to assess PEs, studies assessing safety of PEs, approaches to assist translation of PEs into effective oral, nasal, ocular and vaginal dosage forms and combining PEs with other delivery strategies.

Keywords

absorption enhancers --- sugar-based surfactants --- biocompatibility studies --- transmucosal drug delivery --- intestinal permeation enhancers --- sodium cholate (NaC) --- N-dodecyl-?-D-maltoside (DDM) --- small intestine --- enterocyte --- brush border --- tryptophan --- oral delivery --- insulin --- GLP-1 --- intestinal absorption --- amino acid --- cell-penetrating peptide --- combined microsphere --- chitosan --- cyclodextrin --- nasal delivery --- nose to brain transport --- penetration enhancer --- nasal formulation --- in vivo studies --- nose to brain delivery --- antiepileptic drug --- drug delivery --- block copolymers --- thermogel system --- chitosan derivatives --- amphiphilic polymers --- polymeric micelles --- quaternization --- curcumin --- intestinal delivery --- mucoadhesiveness --- cervicovaginal tumors --- cationic functionalization --- imatinib --- nanocrystals --- in situ hydrogel --- bioenhancer --- cytochrome P450 --- drug absorption enhancer --- efflux --- metabolism --- P-glycoprotein --- pharmacokinetic interaction --- tight junction --- Aloe vera --- gel --- whole leaf --- absorption enhancement --- Caco-2 --- confocal laser scanning microscopy --- F-actin --- FITC-dextran --- tight junctions --- transepithelial electrical resistance --- permeation enhancer --- oral delivery --- formulation --- permeability --- safety --- simulated intestinal fluid --- hydrophobization --- epithelium --- compound 48/80 --- chitosan --- nanoparticles --- mast cell activator --- vaccine adjuvant --- nasal vaccination --- absorption enhancer --- antimicrobial peptide --- Caco-2 --- claudin --- cell-penetrating peptide (CPP) --- drug delivery --- intestinal epithelial cells --- KLAL --- PN159 --- tight junction modulator --- oral macromolecule delivery --- oral peptides --- sodium caprate --- salcaprozate sodium --- epithelial permeability --- epithelial transport --- nasal permeability --- nose-to-brain --- simvastatin --- nanocapsules --- mucoadhesion --- CNS disorders --- chitosan --- nasal --- pulmonary --- drug administration --- absorption enhancers --- nanoparticle --- and liposome --- absorption enhancer --- gemini surfactant --- intestinal absorption --- poorly absorbed drug --- Caco-2 cells --- PTH 1-34 --- teriparatide --- nasal delivery --- pharmacokinetics --- osteoporosis --- man --- sheep --- clinical trial --- preclinical --- Caco-2 --- intestinal absorption --- nanomedicine --- nanoparticle --- oral delivery --- transferrin --- ocular drug delivery --- cornea --- penetration enhancers --- ocular conditions --- ophthalmology --- permeation enhancers --- absorption modifying excipients --- oral delivery --- nasal delivery --- ocular delivery --- vaginal delivery --- transmucosal permeation

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