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Monitoring endogenous GPCRs: lessons for drug design

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196517 Year: Pages: 134 DOI: 10.3389/978-2-88919-651-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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G protein-coupled receptors (GPCRs) are integral membrane proteins forming the fourth largest superfamily in the human genome. Many of these receptors play key physiological roles and several pathologies have been associated with receptor functional abnormalities. GPCRs therefore represent important goals for drug design in pharmaceutical companies since they constitute the target of about one third of the drugs currently on the market. However, endogenous GPCRs are most often difficult to study because of a lack of tools to target them specifically and single out their response to physiological or drug-elicited stimulations. Hence, studies mostly focused on recombinant receptors expressed in a variety of cellular models that do not always closely reflect the receptor natural environment and often deal with levels of expression exceeding by far physiological ranges. Recent technological developments combining for example genetically modified animals and advanced imaging approaches have improved our ability to visualize endogenous GPCRs. To date, trailing receptor activation, subsequent intracellular redistribution, changes in signaling cascade up to integrated response to a drug-elicited stimulation is at hand though the impact of a physiological challenge on receptor dynamics remains a major issue. Data however suggest that the receptor may embrace a different fate depending on the type of stimulation in particular if sustained or repeated. This suggests that current drugs may only partially mimic the genuine response of the receptor and may explain, at least in part, their secondary effects. Commonalities and specificities between physiological and drug-induced activation can thus represent valuable guidelines for the design of future drugs.

Insights into Microbe-Microbe Interactions in Human Microbial Ecosystems: Strategies to be Competitive

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450527 Year: Pages: 116 DOI: 10.3389/978-2-88945-052-7 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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All parts of our body having communication with the external environment such as the skin, vagina, the respiratory tract or the gastrointestinal tract are colonized by a specific microbial community. The colon is by far the most densely populated organ in the human body. The pool of microbes inhabiting our body is known as “microbiota” and their collective genomes as “microbiome”. These microbial ecosystems regulate important functions of the host, and their functionality and the balance among the diverse microbial populations is essential for the maintenance of a “healthy status”. The impressive development in recent years of next generation sequencing (NGS) methods have made possible to determine the gut microbiome composition. This, together with the application of other high throughput omic techniques and the use of gnotobiotic animals has greatly improved our knowledge of the microbiota acting as a whole. In spite of this, most members of the human microbiota are largely unknown and remain still uncultured. The final functionality of the microbiota is depending not only on nutrient availability and environmental conditions, but also on the interrelationships that the microorganisms inhabiting the same ecological niche are able to establish with their partners, or with their potential competitors. Therefore, in such a competitive environment microorganisms have had to develop strategies allowing them to cope, adapt, or cooperate with their neighbors, which may imply notable changes at metabolic, physiological and genetic level. The main aim of this Research Topic was to contribute to better understanding complex interactions among microorganisms residing in human microbial habitats.All parts of our body having communication with the external environment such as the skin, vagina, the respiratory tract or the gastrointestinal tract are colonized by a specific microbial community. The colon is by far the most densely populated organ in the human body. The pool of microbes inhabiting our body is known as “microbiota” and their collective genomes as “microbiome”. These microbial ecosystems regulate important functions of the host, and their functionality and the balance among the diverse microbial populations is essential for the maintenance of a “healthy status”. The impressive development in recent years of next generation sequencing (NGS) methods have made possible to determine the gut microbiome composition. This, together with the application of other high throughput omic techniques and the use of gnotobiotic animals has greatly improved our knowledge of the microbiota acting as a whole. In spite of this, most members of the human microbiota are largely unknown and remain still uncultured. The final functionality of the microbiota is depending not only on nutrient availability and environmental conditions, but also on the interrelationships that the microorganisms inhabiting the same ecological niche are able to establish with their partners, or with their potential competitors. Therefore, in such a competitive environment microorganisms have had to develop strategies allowing them to cope, adapt, or cooperate with their neighbors, which may imply notable changes at metabolic, physiological and genetic level. The main aim of this Research Topic was to contribute to better understanding complex interactions among microorganisms residing in human microbial habitats.

Effects of Mycotoxins on the Intestine

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ISBN: 9783038977827 9783038977834 Year: Pages: 262 DOI: 10.3390/books978-3-03897-783-4 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Public Health
Added to DOAB on : 2019-05-09 17:16:14
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Mycotoxins are secondary metabolites produced by several fungal species. They can contaminate human food and animal feed, and have been a threat for thousands of years. The gastrointestinal tract is the first target when ingesting mycotoxin-contaminated food or feed. As unlikely as it sounds, the investigations concerning the effects of mycotoxins on the intestine are still in their early stages. This book gathers the most recent advances related to the characterization of the intestinal toxicity of mycotoxins. Substantial data assembled on the damage caused to a number of histological structures and functions of the intestine remove any remaining doubt about this organ being a primary target for the toxicity of mycotoxins. An interesting overview of the detrimental effects of mycotoxins on the gut-hosted microbiota—now regarded as a fully-fledged organ associated with the gut—is also given. Finally, outstanding contributions in this book address questions relating to the suitability of current regulations to protect against alterations of the intestine, and to the efficacy assessment of new detoxification strategies using the intestinal toxicity of mycotoxins as a relevant endpoint.

Keywords

mice --- aflatoxin B1 --- intestinal bacterial flora --- response --- Clostridium sp. WJ06 --- deoxynivalenol --- pig --- intestinal morphology --- microbial diversity --- aflatoxin M1 --- ochratoxin A --- intestinal epithelial cells --- tight junction --- permeability --- ileum --- jejunum --- deoxynivalenol --- piglet --- contaminated feed --- tight junction --- aflatoxin B1 --- small intestine --- histopathological lesions --- ultrastructural changes --- toll-like receptors --- T-2 toxin --- enteric nervous system --- pig --- vasoactive intestinal polypeptide --- mycotoxins --- zearalenone --- deoxynivalenol --- histology --- ultrastructure --- large intestine --- pig --- Claviceps --- liver --- digestive tract --- mycotoxin --- sclerotia --- ergot alkaloids --- toxicity --- deoxynivalenol --- Saccharomyces cerevisiae boulardii CNCM I-1079 --- intestine --- transcriptome --- inflammation --- oxidative stress --- lipid metabolism --- fumonisin --- microbiota --- pigs --- MiSeq 16S rDNA sequencing --- intestinal microbiota --- hydrogen-rich water --- lactulose --- Fusarium mycotoxins --- piglets --- functional oligosaccharides --- mycotoxins --- swine --- explant technique --- intestinal morphology --- goblet cells --- deoxynivalenol --- zearalenone --- pig --- colon microbiota --- Lactobacillus --- detoxification --- zearalenone --- doses --- caecal water --- genotoxicity --- pre-pubertal gilts --- atlantic salmon --- deoxynivalenol --- feed --- intestine --- PCR --- proliferating cell nuclear antigen --- suppressor of cytokine signaling --- tight junctions --- Zearalenone --- N-acetylcysteine --- SIEC02 cells --- Mitochondrial apoptosis --- n/a

The Impact of Beverages on Ingestive Behavior

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ISBN: 9783038978121 9783038978138 Year: Pages: 166 DOI: 10.3390/books978-3-03897-813-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Nutrition and Food Sciences --- Biology --- Science (General)
Added to DOAB on : 2019-05-13 09:19:27
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Nutrients is planning a Special Issue focusing on beverages and ingestive behavior. This Special Issue will focus on research related to all aspects of beverage consumption and post-ingestive consequences. There continues to be much controversy surrounding the influence of beverage choice on health outcomes. Research investigating the impact of beverage choice has on human health and post-ingestive consequences continue to grow. We know from the growing body of literature that beverage choice has a substantial impact on metabolism, food reinforcement and eating behaviors.

Biological Efficacy of Natural and Chemically Modified Products against Oral Inflammatory Lesions

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ISBN: 9783038979920 / 9783038979937 Year: Pages: 212 DOI: 10.3390/books978-3-03897-993-7 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2019-06-26 08:44:06
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Oral health is general health. If the oral cavity is kept healthy, the whole body is always healthy. Bacteria in the oral cavity do not stay in the oral cavity, but rather they travel throughout the body and can induce various diseases. Periodontal pathogens are involved in tooth loss. The number of remaining teeth decreases with age. People with more residual teeth can bite food well and live longer with lower incidence of dementia. There are many viruses in the oral cavity that also cause various diseases. Bacteria and viruses induce and aggravate inflammation, and therefore should be removed from the oral cavity. In the natural world, there are are many as yet undiscovered antiviral, antibacterial and anti-inflammatory substances. These natural substances, as well as chemically modified derivatives, help our oral health and lead us to more fulfilling, high quality lives. This Special Issue, entitled “Biological Efficacy of Natural and Chemically Modified Products against Oral Inflammatory Lesions”, was written by specialists from a diverse variety of fields. It serves to provide readers with up-to-date information on incidence rates in each age group, etiology and treatment of stomatitis, and to investigate the application of such treatments as oral care and cosmetic materials.

Keywords

metabolomics --- oral cell --- benzaldehyde --- eugenol --- inflammation --- cytotoxicity --- stomatitis --- recurrent aphthous stomatitis --- oral lichen planus --- CCN2 --- glucocorticoids --- alkaloids --- anti-human immunodeficiency virus (HIV) --- antiviral --- natural product --- human virus --- inflammatory disease --- stomatitis --- periodontitis --- anti-osteoclast activity --- cepharanthin --- herbal medicine --- natural product --- arachidonic acid cascade --- allergic rhinitis --- mice --- quercetin --- thioredoxin --- nasal epithelial cell --- production --- increase --- in vitro --- in vivo --- nutritionally variant streptococci --- antimicrobial susceptibilities --- oral microbiota --- infective endocarditis --- kampo formula --- traditional Japanese herbal medicine --- stomatitis --- mucositis --- Hangeshashinto --- polyphenol --- chromone --- lignin-carbohydrate complex --- alkaline extract --- Kampo medicine --- glucosyltransferase --- angiotensin II blocker --- QSAR analysis --- oral diseases --- dental application --- Chinese herbal remedies --- stomatitis --- periodontitis --- Kampo --- traditional medicine --- Jixueteng --- Juzentaihoto --- technical terms --- gargle --- tongue diagnosis --- mastic --- pathogenic factors --- quantitative structure-activity relationship --- machine learning --- random forest --- natural products --- tumour-specificity --- Kampo medicine --- constituent plant extract --- stomatitis --- oral inflammation --- quantitative structure-activity relationship (QSAR) analysis --- metabolomics

Research of Pathogenesis and Novel Therapeutics in Arthritis

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ISBN: 9783038970651 / 9783038970668 Year: Pages: 366 DOI: 10.3390/books978-3-03897-066-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2019-06-26 08:44:06
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Arthritis has a high prevalence globally and includes over 100 different types, the most common of which are rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and inflammatory arthritis. The exact etiology of arthritis remains unclear and no cure exists. Anti-inflammatory drugs are commonly used in the treatment of arthritis but are associated with significant side effects. Novel modes of therapy and additional prognostic biomarkers are urgently needed for arthritis patients. This book summarizes and discusses the global picture of the current understanding of arthritis.

Keywords

biosimilars --- Th9 lymphocytes --- rheumatoid arthritis --- infliximab --- rheumatoid arthritis --- bone erosion --- osteoblasts --- next-generation sequencing --- bioinformatics --- microRNA --- messenger RNA --- osteoarthritis --- cell signaling --- IL1? --- WNT --- antagonists --- computational modeling --- nitric oxide --- clodronate --- gene expression --- osteoarthritis --- progenitor cells --- SOX9 --- spondyloarthropathies --- inflammation --- mesenchymal stem cells --- visfatin --- IL-6 --- TNF-? --- osteoarthritis --- miR-199a-5p --- Epstein-Barr virus --- glycoprotein 42 --- rheumatoid arthritis --- shared epitope --- triptolide --- rheumatoid arthritis --- basic research --- clinical translation --- osteoarthritis (OA) --- articular cartilage --- molecular pathology --- therapeutics --- rheumatoid arthritis --- antibodies --- collagen --- glycosylation --- disease pathways --- therapy --- experimental arthritis --- TNF? --- etanercept --- infliximab --- adalimumab --- certolizumab pegol --- golimumab --- rheumatoid arthritis --- therapeutic antibody --- structure --- fraxinellone --- collagen-induced arthritis --- rheumatoid arthritis --- inflammatory arthritis --- osteoclastogenesis --- sclareol --- rheumatoid arthritis --- synovial cell --- collagen --- mice --- cytokines --- Th17 --- MAPK --- arthritis --- osteoarthritis --- rheumatoid arthritis --- small-molecule inhibitor --- chondrocytes --- tumor necrosis factor-alpha --- inflammation --- rheumatoid arthritis --- osteoarthritis --- angiogenesis --- cytokines --- chemokines --- early osteoarthritis --- articular cartilage --- proliferation --- fibroblast growth factor 2 --- mitogen activated protein kinase --- transforming growth factor ? --- SMA- and MAD-related protein --- interleukin --- nuclear factor kappa B --- miRNA --- adjuvant arthritis --- arthritis --- biomarkers --- celastrol --- inflammation --- microRNA --- miRNA --- rat --- rheumatoid arthritis --- Traditional Chinese medicine --- tripterine --- triterpenoid --- spinal fusion --- biological --- osteoblast --- osteoclast --- bisphosphonate --- parathyroid hormone --- bone morphogenetic protein --- receptor activator of nuclear factor ?B --- stem cell --- drug delivery system --- anticitrullinated peptide antibodies --- antirheumatic drug --- autoimmune --- disease-modifying --- immunology --- pathology --- rheumatoid factor --- rheumatoid arthritis --- osteoarthritis --- adipokines --- obesity --- rheumatoid arthritis --- osteoarthritis --- anti-arthritis --- biomarkers

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