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Diacylglycerol Kinase Signalling

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453351 Year: Pages: 96 DOI: 10.3389/978-2-88945-335-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2018-02-27 16:16:45
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Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DG), catalyzing its conversion into phosphatidic acid (PA). This reaction attenuates membrane DG levels, limiting the localization/activation of signaling proteins that bind this lipid. Initially recognized as modulators of classical and novel PKC family members, the function of the DGK has further expanded with the identification of novel DG effectors including Ras Guanyl nucleotide-releasing proteins (RasGRP) and chimaerin Rac GTPases. The product of the DGK reaction, PA, is also a signaling lipid that mediates activation of multiple proteins including the mammalian target of rapamycin (mTOR). The DGK pathway thus modulates two lipids with important signaling properties that are also key intermediates in lipid metabolism and membrane trafficking. The DGK family in eukaryotes comprises 10 different members grouped into five different subfamilies characterized by the presence of particular regulatory motifs. These regions allow the different DGK isoforms to establish specific complexes and/or to be recruited to specific subcellular compartments. The subtle regulation of DG and PA catalyzed byspecific DGKs is sensed by a restricted set of molecules, providing the means for spatio-temporal regulation of signals in highly specialized cell systems.In the recent years, multiple studies have unveiled the functions of specific isoforms, their mechanisms of regulation and their participation in different pathways leading to and from DG and PA. Animal models have greatly helped to understand the specialized contribution of DGK mediated signals, particularly in the immune and central nervous systems. Mice deficient for individual DGK isoforms show defects in T and B cell functions, dendritic spine maintenance, osteoclast and mechanical-induced skeletal muscle formation. Studies in flies and worms link DGK mediated DAG metabolism with mTOR- mediated regulation of lifespan and stress responses. In plants DGK mediated PA formation contributes to plant responses to environmental signals.Aberrant DGK function has been recently associated with pathological states, an expected consequence of the essential role of these enzymes in the regulation of multiple tissue and systemic functions. DGK mutations/deletions have been related to human diseases including diabetes, atypical hemolytic-uremic syndrome, Parkinson disease and bipolar disorders. On the contrary DGK upregulation emerges as a non-oncogenic addition of certain tumors and represents one of the main mechanism by which cancer evades the immune attack. As a result, the DGK field emerges an exciting new area of research with important therapeutic potential.

On the Origin and Function of Human NK-like CD8+ T Cells: Charting New Territories

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453962 Year: Pages: 121 DOI: 10.3389/978-2-88945-396-2 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2018-11-16 17:17:57
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Human CD8+ T cells expressing NK receptors and receptors found on innate immune cells, and designated as NK-like or innate CD8+ T cells, have been long considered as terminally differentiated lymphocytes responsible for tissue inflammation and destruction. However, a growing body of knowledge is unveiling that NK-like CD8+ T cells have many, sometimes contrasting, functions. The limited knowledge of the biology of this type of CD8+ T cells and the role they play within peripheral tissues and organs under homeostatic conditions has hampered our understanding of disease and therefore the possible development of disease diagnostic tools and effective immunotherapies. In this Research Topic are presented a variety of topics and views, some of them overlooked for many years, on human NK-like CD8+ T cells, which may open new and novel avenues of research to further our understanding of these polyfunctional T cells.

A living history of immunology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196982 Year: Pages: 62 DOI: 10.3389/978-2-88919-698-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-08-16 10:34:25
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In the highly competitive world of biomedical science, often the rush to publish and to be recognized as "first" with a new discovery, concept or method, is lost in the hurly-burly of the moment, as "the maddening crowd" moves on to the next "new thing". One of the great things about immunology today is that it has only become mature as a science within the last half-century, and especially within the past 35 years as a consequence of the revolution of molecular immunology, which has taken place only since 1980. Consequently, most of those who have contributed to our new understanding of how the immune system functions are still alive and well, and still contributing. Thus, "A Living History of Immunology" collates many stories from the investigators who actually performed the experiments that have established the frontiers of immunology. Accordingly, this volume combats "revisionist science", by those who want to alter history by telling the stories a different way than actually happened. In this regard, one of the good things about science vs. other disciplines is that we have the written record of what was done, when it was done and by whom. Even so, we do not have the complete story or narrative of how and why experiments were done, and what made the differences that led to success. This volume captures and chronicles some of these stories from the past fifty years in immunology.

Immune Checkpoint Molecules and Cancer Immunotherapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889457328 Year: Pages: 197 DOI: 10.3389/978-2-88945-732-8 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2019-01-23 14:53:43
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For the faultless function of the immune system, tight regulation of immune cell activation, immuno-suppression and the strength and efficiency of the immune response is essential. Immune checkpoint (ICP) molecules can amplify or dampen signals that lead to the modulation of specific immune activities. Under physiological conditions, immune checkpoints are essential to prevent autoimmune manifestations and to preserve self-tolerance. They help modulate immune responses by either promoting or inhibiting T-cell activation. However, in the context of cancer, malignant cells can dysregulate the expression of immune checkpoint proteins on immune cells in order to suppress anti-tumor immune responses and to gain immune resistance. Moreover, tumor cells themselves can also express some checkpoints proteins, thereby enabling these cells to externally orchestrate immune regulatory mechanisms. Several recent studies have confirmed that the expression of immune checkpoints could be an important prognostic parameter for cancer development and for patient outcome. Therefore, cancer immunotherapy based on the modulation of immune checkpoint molecules alone, or in combination with conventional tumor therapy (chemo- or/and radiotherapy), is now in focus as a means of developing new therapeutic strategies for different types of cancer. The two well-known molecules – CTLA4 and PD-1 - serve as important examples of such checkpoint proteins of important therapeutic potential. Thus far, inhibitors of CTLA4 and PD-1 have been approved to treat only a limited number of malignancies (e.g. malignant Melanoma, Non-Small Cell Lung Cancer). Many others are currently under investigation and the list of immune checkpoint molecules for potential therapeutic targeting is still growing. However, the clinical response to inhibitors of checkpoint molecules is not sufficient in all cases. Therefore, further studies are needed to improve our knowledge of such immunomodulatory proteins and their associated signaling pathways. Several key signaling pathways which are involved in the regulation of expression of checkpoint molecules in immune cells and in cancer cells have already been identified including MAPK, PI3K, NF-kB, JAKs and STATs. These (and future discovered) signaling pathways could give rise to the development of new strategies for modulating the expression of ICPs and thereby, improving anti-cancer immune responses. The main aim of the Research Topic is to collect novel findings from scientists involved in basic research on immune checkpoints as well as in translational studies investigating the use of checkpoint inhibtors in immunotherapy in experimental settings. We welcome the submission of Review, Mini-Review and Original Research articles that cover the following topics: 1. Molecular mechanisms underlying regulation of ICP expression in immune and/or cancer cells.2. Characterization of signaling pathways downstream ICP molecules.3. Cellular responses to ICP blockade.4. Identification of new compounds interfering with ICP expression and/or signaling.5. ICP-mediated interactions between cancer cells and immune cells. 6. Functional links between ICP and cytokines/chemokines.7. Molecular mechanisms of ICP inhibition in the context of experimental cancer immunotherapy.

Marine Glycosides

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ISBN: 9783038979029 9783038979036 Year: Pages: 264 DOI: 10.3390/books978-3-03897-903-6 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2019-05-09 17:16:14
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In recent years, there has been a steady increase in the publication of papers on the chemistry, biology, and potential clinical uses of marine glycosides. Indeed, more than half of the papers published in this field are less than a decade old. Glycosides have been isolated from species as diverse as algae, fungi, anthozoans, and echinoderms. Even fish of the genus Pardachirus produce glycosides, which they use as shark repellents.The major interest in these compounds as potential drugs stems from their broad spectrum of biological effects. They have been shown to have antimicrobial, antifungal, anti-inflammatory, immune modulatory, and anticancer effects. The anticancer effects of marine glycosides include cell cycle suppression, the induction of apoptosis, and the inhibition of migration, invasion, and metastasis, as well as antiangiogenesis. Marine glycosides influence membrane permeability and have been shown to influence membrane transport at the molecular level through effects on transport carriers and pumps, as well as effects on ligand-gated and voltage-gated channels. Various marine glycosides have been shown to activate sphingomyelinase and ceramide synthesis, to inhibit topoisomerase activity, receptor tyrosine kinase activity, and multidrug resistance protein activity, and to antagonize eicosanoid receptors.This Special Issue covers the entire scope of marine organism-derived glycosides that are of potential value as pharmaceutical agents or leads. These include, but are not limited to, tetracyclic triterpene glycosides, other triterpene glycosides, steroid glycosides, and glycosides of non-isoprenoid aglycones.

Biological Potential and Medical Use of Secondary Metabolites

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ISBN: 9783039211876 / 9783039211883 Year: Pages: 284 DOI: 10.3390/books978-3-03921-188-3 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-08-28 11:21:27
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Many macro and micro species, from terrestrial and aquatic environments, produce structurally unique compounds and, in many countries, still are the primary sources of medicines. In fact, secondary metabolites are an important source of chemotherapeutic agents but are also lead compounds for synthetic modification and the optimization of biological activity. Therefore, the exploitation of secondary metabolites, or their inspired synthetic compounds, offers excellent opportunities for the pharmaceutical industry. This Medicines Special Issue focuses on the great potential of secondary metabolites for therapeutic application. The Special Issue contains 16 articles reporting relevant experimental results, and an overview of bioactive secondary metabolites, their biological effects, and new methodologies that improve and accelerate the process of obtained lead compounds with regard to new drug development. We would like to thank all 83 authors, from all over the world, for their valuable contributions to this Special Issue.

Keywords

Juniperus --- secondary metabolites --- diterpenes --- flavonoids --- lignans --- cytotoxic --- antitumor --- antibacterial --- amentoflavone --- deoxypodophyllotoxin --- frankincense --- Boswellia --- cembranoids --- cneorubenoids --- boswellic acids --- molecular docking --- Scabiosa --- flavonoids --- iridoids --- pentacyclic triterpenoids --- antioxidant --- anti-inflammatory --- antibacterial --- anticancer --- Cordyceps militaris --- xanthine oxidase --- antioxidant --- antibacterial --- cordycepin --- GC-MS --- Artemisia species --- Artemisia vachanica --- artemisinin --- HPLC-PAD --- Tajikistan --- Malus x domestica --- Tuscany --- ancient varieties --- nutraceutics --- antioxidants --- polyphenols --- sugars --- pectin --- defensins --- secondary metabolites --- plant defense --- antimicrobial and anticancer activity --- medicine --- innate immunity --- cannabis --- cannabinoids --- therapeutics --- toxicology --- analytical determination --- legalization --- natural products --- biosynthetic gene clusters --- secondary metabolites --- antiSMASH --- Mitragyna speciosa --- kratom --- secondary metabolites --- therapeutic uses --- toxicology --- analysis --- Maytenus chiapensis --- Celastraceae --- quinonemethide triterpenoids --- pristimerin --- tingenone --- HPLC-PDA --- Ocimum sanctum --- Lamiaceae --- (-)-rabdosiin --- cytotoxic activity --- triterpenoids --- phenolic derivatives --- nanoemulsion --- essential oils --- vector control --- infectious diseases --- TCM --- phytochemistry --- LC-MS/MS --- antioxidant activity --- ABTS --- DPPH --- FRAP --- ascorbic acid --- EGCG --- total phenolics --- antimicrobial activity --- sargaquinoic acid --- sarganaphthoquinoic acid --- antiplasmodial --- malaria --- PPAR-? --- sargahydroquinoic acid --- sarganaphthoquinoic acid --- sargachromenoic acid --- inflammation --- bowel diseases --- secondary metabolites --- biological activities --- medicinal applications --- plants --- seaweeds

Bioactive Compounds from Marine-Derived Aspergillus, Penicillium, Talaromyces and Trichoderma Species

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ISBN: 9783038979807 / 9783038979814 Year: Pages: 134 DOI: 10.3390/books978-3-03897-981-4 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Microbiology
Added to DOAB on : 2019-06-26 08:44:06
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The importance of bioactive natural compounds in pharmacology and other biotechnological fields has stimulated the scientific community to explore new environmental contexts and their associated microbial diversity. As the largest frontier in biological discovery, the sea represents a significant source of organisms producing novel secondary metabolites with interesting bioactivities. Of the available biological material, fungi have received increasing consideration, both due to their pervasive occurrence in varying habitats as well as their aptitude to develop symbiotic associations with higher organisms in numerous contexts. In many cases, fungal strains have been reported as the real producers of drugs originally extracted from marine plants and animals. Due to the constantly increasing number of marine-derived fungi yielding valuable bioactive products, it is now appropriate to present these findings to a recipient audience in a more organized form. This Special Issue of Marine Drugs, entitled “Bioactive Compounds from Marine-Derived Aspergillus, Penicillium, Talaromyces, and Trichoderma Species"" is specifically focused on a few genera of ascomycetous fungi which are widespread regarding marine contexts and are particularly inclined to establishing symbiotic relationships. For this project, we welcome submissions of full research papers, short notes, and review articles reporting the discovery and characterization of products showing antibiotic, antitumor, antiviral, insecticidal, antimalarial, antifouling, antioxidant, plant growth-promoting and/or resistance-inducing, as well as other less-exploited activities.

Chemical Biology of Sterols, Triterpenoids and Other Natural Products: A Themed Issue in Honor of Professor W. David Nes on the Occasion of His 65th Birthday

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ISBN: 9783038974161 / 9783038974178 Year: Pages: 256 DOI: 10.3390/books978-3-03897-417-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2019-06-26 08:44:06
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Sterols and other isoprenoids are of great interest for their molecular structure and function in cell architecture and evolution, as well as for their importance in medicine and agriculture. Molecules’ 2019 Festschrift Special Issue in honor of the 65th birthday of Prof. W. David Nes, an internationally recognized chemical biologist and recipient of the George Schroepher medal for sterol research, focuses on recent developments in the chemistry, biosynthesis, and function of these polycyclic natural products. This volume of Molecules contains 16 leading-edge review articles and original research contributions from an international cast of scientists. This volume is grouped into three sections: (i) isoprenoid metabolome and diversity, (ii) clinical evaluation of sterol and triterpene structures and biosynthesis, and (iii) methods and synthesis of steroids and other compounds. The volume will be a valuable reference tool for those who study medicinal chemistry, protein chemistry, and biochemistry of isoprenoid lipids.

Keywords

Zingiber officinale --- gingerols --- cytotoxic activity --- oleanolic acid --- high-fat high-carbohydrate diet --- pre-diabetes --- glucose homeostasis --- insulin resistance --- atherosclerosis --- ROS --- HUVECs --- LOX-1 --- alkaloid --- granatane --- N-methylcadaverine --- N-methylpiperidine. reductive deamination --- Mucorales --- Rhizopus arrhizus --- sterol pattern --- antifungal effectivity --- gas chromatography-mass spectrometry (GC-MS) --- posaconazole --- sterol biosynthesis --- sterol 14?-demethylase --- sterol C24-methyltransferase --- mechanism-based inactivators --- antifungals --- azoles --- antiparasitic drugs --- human African trypanosomiasis --- Chagas disease --- synthesis --- squalene cyclase --- cycloartenol synthase --- triterpene --- fern --- Polystichum --- terpene --- isoprenoid --- divalent metal co-factor ligation --- antioxidant --- cholesterol --- degeneration --- oxysterol --- retina --- Smith-Lemli-Opitz syndrome --- algal sterols --- ergosterol biosynthesis --- infectious disease --- lipidomics --- oxyphytosterol --- pharmacognosy --- phytosterol --- sterolomics --- lupeol --- keratinocytes --- fibroblasts --- wound healing --- cell migration --- UV-radiation --- ZnO --- toxicity --- sterol content --- cholesterol --- leishmania --- solanaceae --- withanolides --- aurelianolides --- phytosterols --- mesocarp --- oilseed --- maturity --- pod-blast --- ?-tocopherol --- oil bodies --- campesterol --- stigmasterol --- ?-sitosterol --- sterol --- C4-demethylation complex (C4DMC) --- 4-methylsterol --- hormone --- steroid --- development --- genetic disease --- bile alcohol --- cholestanoic acid --- oxysterol --- sterolomics --- enzyme-assisted derivatization --- electrospray ionization-mass spectrometry --- Girard reagent --- n/a

Isolation and Structure Elucidation of Bioactive Compounds (Dedicated to the memory of the late Professor Charles D. Hufford)

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ISBN: 9783038977803 9783038977810 Year: Pages: 276 DOI: 10.3390/books978-3-03897-781-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-04-25 16:37:17
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Abstract

We are very pleased to introduce the Book Version of our Special Issue in Molecules dedicated to the memory of the late Professor Dr. Charles D. Hufford. The issue has been a huge success, with 22 full-length peer-reviewed papers and a tribute by Professor Alice M.Clark. Authors, reviewers, and collaborators from many countries across the worldhave contributed to this endeavour, and we are truly grateful to all. This Special Issue isrepresentative of the broad impact that “Charlie” had on the field of bioactive naturalproducts. This Special Issue comprises papers from Professor Hufford’s former students,colleagues, and collaborators throughout the world who have utilized a wide array ofstate-of-the-art techniques to examine diverse natural sources to isolate and identify avariety of natural products with a wide spectrum of biological activities, including somenew microbial transformations and insights into bioactive molecules. Many new bioactive compounds are described and reported here for the first time. Bioactivities reportedinclude cytotoxicity, antimicrobial activity, anti-inflammatory activity, antileishmanialactivity, antitrypanosomal activity, antimalarial activity, analgesic activity, and beneficialliver activities, just to name a few. This Special Issue will undoubtedly have a lasting impact on the field of bioactive natural products, as exemplified by the career of Dr. Hufford.Lastly, without the timely and outstanding contributions from all of you, this Special Issue would not have been possible. We thank you all very much for your contributions and your time devoted to this Special Issue in memory of a special person. Finally, we express ourgratitude and thanks to the journal Molecules and their excellent team of expert reviewers for giving us the support and opportunity to make this Special Issue a huge success!

Keywords

fusidic acid --- Cunninghamella echinulata --- C-26-oxidation --- C-27-oxidation --- Morus alba L. --- aldose reductase inhibitor --- neuroprotective agent --- natural products --- Mitracarpus scaber Zucc. --- pentalogin --- anti-inflammatory --- MS/MS --- Il-8 --- Crinum amabile --- augustine N-oxide --- buphanisine N-oxide --- biological activities --- Cryptococcus neoformans --- cryptococcosis --- HepG2 --- Prosopis glandulosa --- prosopilosidine --- amphotericin B --- fluconazole --- resveratrol --- dietary supplement --- gastro-resistant --- microparticles --- obesity --- HPLC --- Jatropha pelargoniifolia --- alkaloids --- flavonoids --- coumarinolignans --- diterpenes --- anti-inflammatory --- analgesic --- antipyretic --- Cochlospermum vitifolium --- Cochlospermaceae --- flavonoids --- lignans --- aromatic compounds --- carotenoids --- sterols --- liver activity --- Arthrinium sp. --- chromone --- polyketide --- antioxidant activity --- Rubiaceae --- jenipapo --- HPLC-ESI-IT-MS/MS --- flavonoids glycosides --- Baccharis --- antimalarial activity --- antitrypanosomal activity --- insecticidal activity --- GC/MS --- DNA barcoding --- microscopy --- antibacterial --- channel catfish --- columnaris disease --- Flavobacterium columnare --- stilbenes --- muscadine --- pyranoanthocyanin --- anti-leishmanial activity --- Leishmania donovani --- maleimides --- cytotoxicity --- SAR --- phlorogluciniol --- acylphloroglucinol --- anti-inflammatory --- iNOS --- NF-?B --- endophytic fungi --- sesterterpene --- cytotoxic activity --- pancreatic cancer --- Stevia rebaudiana --- diterpene glycosides --- rebaudioside A isomers --- 13(S)-hydroxyatisenoic acid derivative --- iso-stevioside X-ray structure --- Litsea cubeba --- cytotoxicity --- isolation and elucidation --- lignans --- antimicrobial resistance --- multi-drug resistant (MDR) --- methicillin resistant Staphylococcus aureus (MRSA) --- Zingiber monatnum --- terpenes --- (E)-8(17),12-labdadiene-15,16-dial --- zerumbol --- microbial transformation --- hop prenylflavanone --- isoxanthohumol --- cardiomyogenesis --- factor VII --- factor X --- inflammation --- thrombosis --- vasculogenesis --- herbal medicine --- n/a --- Nemania --- Xylariaceae --- Torreya taxifolia --- plant pathogenic and endophytic fungi --- cytochalasins --- malaria --- cytotoxicity --- phytotoxicity --- acacetin 7-methyl ether --- acacetin --- monoamine oxidase-A --- monoamine oxidase-B --- molecular docking --- molecular dynamics --- neurological disorder --- Turnera diffusa

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