1,721,043 research outputs found

    5,6-Dihydroxyindole-2-carboxylic acid, a diffusible melanin precursor, is a potent stimulator of lipopolysaccharide-induced production of nitric oxide by J774 macrophages

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    Pre-incubation of J774 murine macrophages with 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a diffusible intermediate in the biosynthesis of eumelanins, leads to a marked increase in the levels of nitric oxide (NO) produced by lipopolysaccharide (LPS)-induced NO-synthase (iNOS). The effect varies with DHICA concn., being max. at a concn. of 1 × 10-6M, and is suppressed by the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). No stimulation is obsd. when macrophages are exposed to DHICA after activation with LPS, indicating that the indole does not affect the catalytic activity of iNOS. These results point to a hitherto unrecognized role of DHICA as a chem. messenger mediating interaction between active melanocytes and macrophages in epidermal inflammatory and immune responses

    From IL-15 to IL-33: the never-ending list of new players in inflammation. Is it time to forget the humble aspirin and move ahead?

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    The study of the inflammatory response has seen a tremendous expansion over the last 30 years. Advancements in technology and better knowledge of the ethiopathogenesis of several inflammatory conditions have facilitated this process allowing researchers to almost reach the core of problem. Thus, we now know that inflammation can be manifested in many different ways depending on the context that has elicited it. Viral and infectious, allergic and autoimmune, carcinogenic and resolutive are just a few examples of how inflammation can disguise itself. However, and most intriguingly, it appears that the more we try to discover "an ideal target" and delineate borders for a specific class of inflammatory conditions the more we find similarities, overlaps or often links that we did not predict. These somehow disappointing findings have pushed researchers towards a frantic search for new and more "reliable" targets. As result, we have recently seen a surge of many novel mediators of inflammation. If we just limit our focus to inflammatory cytokines, the main topic of this commentary, the list seems never-ending: IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-27 and IL-33. Are these cytokines destined to supersede prostaglandins and other autacoids for their key role in inflammation? Are we going to see a cheap and effective alternative to aspirin on the supermarket shelves in the next few years? Here we summarize the most recent findings on the biological effects of these new inflammatory cytokines and discuss how these discoveries might influence our current view on therapeutic approaches to treat inflammatio

    Porrigenins A and B, novel cytotoxic and antiproliferative sapogenins isolated from Allium porrum

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    Four new sapogenins, porrigenins A (2a) and B (3a), identified as (25R)-5 alpha-spirostan-2 beta,3 beta,6 beta-triol and (25R)-2-oxo-5 alpha-spirostan-3 beta,6 beta-diol, respectively, and neoporrigenins A (2b) and B (3b) were also isolated from Allium porrum. In addition, the known agigenin (1a) and its 25S epimer, neoagigenin (1b), were also identified. Their structure elucidation was provided by comprehensive spectroscopic analyses. Compounds 1a, 2a, and 3a exhibited cytotoxicity and high antiproliferative activity on four different tumor cell lines in vitro

    Structure and absolute stereochemistry of the new cyclolinteinol and cyclolinteinol acetate, macrophage activation modulators

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    wo novel sesterterpenes, cyclolinteinol (5) and cyclolinteinol acetate (6), have been isolated from the Caribbean sponge Cacospongia cf. linteiformis. Their structures and absolute stereochemistry were determined using spectroscopic and chemical methods. The new compounds (5, 6) and the related compounds 1-3, previously isolated from the sponge, strongly inhibited NO production by LPS-stimulated murine macrophages J774

    Quisquis Amat Valeat! (Whoever Loves, May He be Well) Why Love and Passion Are Important for the Well-Being of the Immune System

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    “Quisquis amat valeat; pereat qui non-scit amare; bis tanti pereat, quisquis amare vetat”—(Whoever loves, may he be well; may he perish who does not know how to love; may he perish twice as much whoever forbids loving). This graffiti was found in the old city of Pompei. The author is unknown. Possibly a poet but quite possibly an ordinary citizen who in the spur of their passion wanted to share with everyone a pearl of wisdom. Amare in Latin is “to love” and, as in English, it is not just about sex or romance, but also about passion for a cause or an ideal. The Latins knew that to be in love, to have a passion, is to be healthy in the body and as well as in the mind. In this article, I hypothesize that the lack of passion and love in life is one of the main causes of modern diseases and specifically immune/inflammatory diseases. I will explore in layman terms the limitations of specifically focusing on controlling bodily functions without considering the social and emotional dimensions of one's life. Lastly, I will highlight the importance of cooperative research, engagement with the public and education as the way forward for a more effective and democratic model for new socially inclusive therapies

    The immunomodulatory effects of social isolation in mice are linked to temperature control

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    Living in isolation is considered an emerging societal problem that negatively affects the physical wellbeing of its sufferers in ways that we are just starting to appreciate. This study investigates the immunomodulatory effects of social isolation in mice, utilising a two-week program of sole cage occupancy followed by the testing of immune-inflammatory resilience to bacterial sepsis. Our results revealed that mice housed in social isolation showed an increased ability to clear bacterial infection compared to control socially housed animals. These effects were associated with specific changes in whole blood gene expression profile and an increased production of classical pro-inflammatory cytokines. Interestingly, equipping socially isolated mice with artificial nests as a substitute for their natural huddling behaviour reversed the increased resistance to bacterial sepsis. Together these results suggest that the control of body temperature through social housing and huddling behaviour are important factors in the regulation of the host immune response to infection in mice and might provide another example of the many ways by which living conditions influence immunity.Crown Copyright © 2022 Published by Elsevier Inc. The attached document (embargoed until 26/02/2023) is an author produced version of a paper published in BRAIN, BEHAVIOR, AND IMMUNITY uploaded in accordance with the publisher’s self-archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it

    Peripheral control of psychiatric disorders: Focus on OCD. Are we there yet?

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    “We are all in this together” – we often hear this phrase when we want to flag up a problem that is not for a single individual but concerns us all. A similar reflection has been recently made in the field of mental disorders where brain-centric scientists have started to zoom out their brain-focused graphical representations of the mechanisms regulating psychiatric diseases to include other organs or mediators that did not belong historically to the world of neuroscience. The brain itself – that has long been seen as a master in command secluded in its fortress (the blood brain barrier), has now become a collection of Airbnb(s) where all sorts of cells come in and out and sometimes even rearrange the furniture! Under this new framework of reference, mental disorders have become multisystem pathologies where different biological systems – not just the CNS –contribute ‘all together’ to the development and severity of the disease. In this narrative review article, we will focus on one of the most popular biological systems that has been shown to influence the functioning of the CNS: the immune system. We will specifically highlight the two main features of the immune system and the CNS that we think are important in the context of mental disorders: plasticity and memory

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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