Precision Nutrition in Chronic Inflammation

The molecular foundation of chronic in fl ammatory diseases (CIDs) can differ markedly between individuals. As our understanding of the biochemical mechanisms underlying individual disease manifestations and progressions expands, new strategies to adjust treatments to the patient ’ s characteristics will continue to profoundly transform clinical practice. Nutrition has long been recognized as an important determinant of in fl ammatory disease phenotypes and treatment response. Yet empirical work demonstrating the therapeutic effectiveness of patient-tailored nutrition remains scarce. This is mainly due to the challenges presented by long-term effects of nutrition, variations in inter-individual gastrointestinal microbiota, the multiplicity of human metabolic pathways potentially affected by food ingredients, nutrition behavior, and the complexity of food composition. Historically, these challenges have been addressed in both human studies and experimental model laboratory studies primarily by using individual nutrition data collection in tandem with large- scale biomolecular data acquisition (e.g. genomics, metabolomics, etc.). This review highlights recent fi ndings in the fi eld of precision nutrition and their potential implications for the development of personalized treatment strategies for CIDs. It emphasizes the importance of computational approaches to integrate nutritional information into multi- omics data analysis and to predict which molecular mechanisms may explain how nutrients intersect with disease pathways. We conclude that recent fi ndings point towards the unexhausted potential of nutrition as part of personalized medicine in chronic in fl ammation

dolls/puppets in threat scenarios

Puppen in Bedrohungsszenarien – so lautet der Themenschwerpunkt der ersten Ausgabe der interdisziplinären online-Zeitschrift "denkste: puppe / just a bit of: doll" zu Mensch-Puppen-Diskursen (Akronym: de:do). Die Bezeichnung ‚Puppe’ steht dabei für anthropomorphe ,Wesen’ und Artefakte in all ihren unterschiedlichen Erscheinungsformen und der Begriff der Bedrohung wird hier weit gefasst. Ausgangspunkt der Entscheidung für diesen Fokus war die Annahme, dass Puppen und puppenaffinen Artefakten sowohl in Zeiten existenzieller Bedrohung als auch in Phasen innerpsychischer Beunruhigung und Irritation eine besondere Bedeutung zukommt. Die hier einbezogenen Beiträge stammen aus unterschiedlichen Fachdisziplinen und eröffnen in der bewusst nicht disziplinär ausgerichteten Zusammenstellung reizvolle multiperspektivische Mensch-Puppen-Diskurse. Dabei sind nicht nur die hier angesprochenen Themenbezüge, sondern auch die jeweiligen methodischen Zugänge ausgesprochen heterogen. So werden Puppen-Narrative aufgegriffen, die beispielsweise innerhalb der Literaturwissenschaft an die lange Tradition von Puppen-Erzählungen anknüpfen, aber auch solche, die aktuell in den Diskursen über Zukunftsszenarien und neue Technologien mittels verschiedener medialer Formate und/oder künstlerischer Aktionen für Diskussionsstoff sorgen. Ein erster thematischer Fokus liegt auf der Bedeutung von Puppen im Zuge der Erfahrung von Bedrohung und Verlusten im Kontext von Krieg, Flucht und Verfolgung in politisch unsicheren Zeiten. Hier werden aus verschiedenen fachdisziplinären Perspektiven unterschiedliche Facetten von Bedrohungsszenarien angesprochen. So geht es aus theaterwissenschaftlicher Sicht um zwei Inszenierungen aus dem Bereich des Objekt- und Materialtheaters, in denen bedrohliche Kriegsdarstellungen mittels Plastikpuppen bzw. amorphen Materials aufbereitet werden. Aus psychologischer Perspektive kommen Rollen und Funktionen von Puppen als Übergangsobjekte im Kontext von Umbrüchen, Krieg und Gewalt zur Sprache. In zwei literaturwissenschaftlichen Beiträgen wird jeweils ein Roman aus der Kinder- und Jugendliteratur analysiert, in denen in einem Fall eine Puppe zur psychischen Stabilisierung der literarischen Protagonistin beiträgt und im anderen Fall das Schicksal der Puppe die Geschichte von Abschied und letztendlicher Vernichtung ihrer Besitzerin erzählt und symbolisiert. Und schließlich geht es um den Stellenwert von Puppen und Teddys in verschiedenen Kinderzeitschriften, die – in den politisch unsicheren Zeiten zwischen und nach den beiden Weltkriegen – Identifikationsfiguren und Interaktionspartner für Kinder sein können. Ein zweiter Fokus thematisiert Puppen und ihre Narrative im Kontext verschiedener aversiver Erfahrungen sowie in Zeiten psychischer Irritation. So geht es zum einen um die literaturwissenschaftliche Sicht auf die Bedeutung und Wirkung von Puppen in zwei ‚klassischen’ Puppenerzählungen: „"Nussknacker und Mausekönig" von E.T.A. Hoffmann und "Romeo und Julia auf dem Dorfe" von Gottfried Keller. Zum anderen werden in verschiedenen Beiträgen Entgrenzungs-, Transformations- und Identitätsfragen in Mensch-Puppen-Bezügen aus medien- und kunstwissenschaftlicher sowie kinderliterarischer Perspektive angesprochen, in denen Puppen in Gestalt von Androiden, Kunstwesen oder anthropomorphen Figuren agieren und dabei selber Irritationen auslösen oder Versuche darstellen, Antworten auf beunruhigende Fragen zu finden. Über den Themenschwerpunkt hinaus finden sich zudem eine Reihe weiterer Beitragsformen zu verschiedenen puppenbezogenen Themen und Praxen, die noch einmal das breite Spektrum unterschiedlicher Puppen-Narrative und Zugangsformen dokumentieren: So beschäftigt sich ein freier Beitrag mit dem Puppenspiel als strukturiertes Therapieangebot für Kinder, bei den Miszellen findet sich eine Skizze zu Marlene Dietrich und ihren Puppen sowie ein kurzer Essay zu einer biographischen Erinnerung, ein Interview mit der Begründerin des Berliner Puppentheaters bubales veranschaulicht Möglichkeiten der dramatischen und poetischen Umsetzung von Puppen-Themen, im Diskussionsforum wird ein kritischer Blick auf "Barbie als Diskursmaschine" geworfen und eine Rezension zum Ausstellungskatalog "From Her Wooden Sleep von Ydessa Hendels" lotet Chancen und Grenzen der künstlerischen Arbeit mit Puppen-Artefakten aus.Dolls / Puppets in Threat Scenarios – this is the topic focus of the first issue of the interdisciplinary online magazine "denkste: puppe / just a bit of: doll" on human-doll discourses (acronym: de: do). The term ’doll’ stands for anthropomorphic ’beings’ and artifacts of all kinds and the concept of threat is broadly defined. This focus was stimulated by the assumption that dolls and doll-related artifacts are of particular importance in times of existential threat as well as in phases of inner psychic anxiety and irritation. Yet, the basically ambiguous character of the doll does not necessarily determine a clear effect, so that its usability always involves a certain blurriness and ambivalence. In threatening and adverse situations dolls can act as companions and significant (transitional) objects, thus allowing psychic stabilization, security, and attachment as well as enabling (inner) autonomy, agency, and developmental processes. But dolls can also be a crucial component of threat scenarios themselves and act frightening in this function. All this applies not only to material and real existing dolls and puppets, but also to dolls as literary and / or media figures as well as to doll narratives of any kind. The articles included here come from different disciplines and open up an appealing and deliberately non-disciplinary oriented human-doll discourse from multiple perspectives. Accordingly, the relevant themes as well as the respective methodological approaches are highly heterogeneous. Thus, some contributions follow the long tradition of doll narratives in literature while others discuss currrent topics and discourses on future scenarios and new technologies by means of various doll-related media formats and / or art performances. A first thematic focus is on the significance of dolls in experiencing threats and losses in the context of war, flight and persecution in times of political uncertainty. Here, different facets of threat scenarios are addressed from different disciplinary perspectives. From the field of object and material theater two productions are introduced in which menacing war scenes are processed by means of plastic dolls or amorphous material. From a psychological perspective, dolls are discussed in their roles and functions as transitional objects within the context of upheaval, war and violence. Furthermore, two literary contributions analyze novels from children’s and youth literature. One story deals with a doll which contributes to the psychological stabilization of the literary protagonist. The other story tells of a girl and her doll which symbolizes the final farewell and eventual annihilation of the (Jewish) girl. Finally, the role of dolls and teddy bears in various children’s magazines is exemplified, which serve as identification figures and interaction partners for children in the politically unstable times between and after the two World Wars. A second focus deals with dolls and their narratives in the context of various aversive experiences as well as in times of psychological irritation. Two contributions analyze the meaning and effect of dolls in two ’classical’ doll narratives from a literary perspective: "Nussknacker und Mausekönig" by E.T.A. Hoffmann and "Romeo und Julia auf dem Dorfe" by Gottfried Keller. Further contributions address questions of ego dissolution, transformation and identity processes in human-doll relations from various perspectives such as media, art and children’s literature. Here, dolls appear as androids, artistic or anthropomorphic figures which cause irritation themselves or attempt to find answers to disturbing human-doll questions. In addition to the main topic, there are also a number of other sections and types of contributions on various doll-related topics and practices which once again document the wide range of doll narratives and possible forms of access: For example, a free contribution deals with doll play as a structured therapy for children, the miscellaneous section includes a portrait of Marlene Dietrich and her dolls as well as a short essay on a biographical reminiscence, an interview with the founder of the Berlin Puppet Theater bubales illustrates the possibilities of dramatic and poetic realization of puppet and doll narratives, a critical view on "Barbie as a discourse machine" is presented in the discussion forum and a review of the exhibition catalog "From Her Wooden Sleep by Ydessa Hendels" explores opportunities and limits of artistic work with doll artifacts

dolls/puppets as miniatures - more than small

Weitere Hrsg.: Jana Mikota, Philipp SchmerheimDer Themenschwerpunkt der zweiten Ausgabe von de:do lautet: Puppen als Miniaturen – mehr als klein. Puppen und ihre Kontexte beanspruchen hier, ’mehr’ als nur verkleinerte Varianten oder Repliken menschlicher Lebenswelten zu sein. Nicht von ungefähr gelten sie als ein ’Fundort der Größe’ (Bachelard). Als ’kleine Formate’ generieren sie Bilder und Narrative der eigenen Art, die in Funktion und Wirkung offen sind: so bewegen sie sich zwischen Abbildung, Verdichtung und Transformation von Realität, sind Ausdruck von Sehnsüchten und/oder Kontrollbedürfnissen ihrer ErschafferInnen, lösen Bezauberung, Verwunderung oder Befremden aus und ermöglichen ganzheitliche Weltzugänge und Erkenntnis über innere Zusammenhänge. Einmal mehr erweisen sich Puppen als Miniaturen und im Kontext miniaturisierter Welten als hybride Objekte, aufgeladen mit vielerlei Symbolik und Bedeutungsüberschuss. Die Zusammenschau der höchst unterschiedlichen Beiträge im vorliegenden Heft vermittelt eine Ahnung von möglichen Spannungsverhältnissen – zwischen ’klein’ und ’groß’, ’Sichtbarem’ und ’Verstecktem’, ’Realität’ und ’Fiktion’, ’Mimesis’ und ’Poetik’. Das heterogene Themenspektrum unterstreicht die subtile Bedeutung der Puppe als einem besonderen Markenzeichen der ’kleinen Form’ in vielerlei Disziplinen. Die Beiträge stammen aus so unterschiedlichen Fächern bzw. interdisziplinär offenen Fachkulturen wie Archäologie, Anthropologie, Volkskunde, Kinder- und Jugendliteratur, Kunstgeschichte, Spielzeugkunde, Animationsfilm, Bildende Kunst, Mode-Design, Forensik. Ein Interview mit einer jungen Künstlerin, Miszellen und Rezensionen ergänzen die Themenvielfalt.The focus topic of the second edition of the journal denkste: puppe / just a bit of: doll (de:do), a multidisciplinary, peer reviewed online journal for human-doll discourses is: dolls/puppets as miniatures - more than small. Dolls/puppets and their contexts claim to be ’more’ than just miniaturized variants or replicas of human worlds. Thus, it is not by chance that they are regarded as a ’place to find greatness’ (Bachelard). As ’small formats’, they generate images and narratives of their own kind which are open in function and effect: they oscillate between representation, condensation and transformation of reality, expressing longings and/or control needs of their creators and triggering enchantment, amazement or alienation while enabling a holistic access to the world and insight into inner contexts. Arguing in this line, dolls/puppets prove to be miniatures and – in the context of miniaturized worlds –hybrid objects, charged with all sorts of symbolism and excess of meaning. The synopsis of the highly diverse contributions in this issue gives us an idea of possible tensions – between ’small’ and ’large’, ’visible’ and ’hidden’, ’reality’ and ’fiction’, ’mimesis’ and ’poetics’. The heterogeneous range of topics underlines the subtle significance of the doll/puppet as a special trademark of the ’small form’ in many disciplines. The contributions come from subjects as diverse as diverse as archeology, anthropology, folklore, children’s and youth literature, art history, toy studies, animated film, fine arts, fashion design, forensics. An interview with a young artist, miscellaneous aspects as well as reviews complete the variety of topics

Die Rolle der Nikotinursäure in metabolischer Entzündung und Typ 2 Diabetes

There is high knowledge of tryptophan - and niacin metabolism in metabolic inflammation and type 2 diabetes (T2D). However, effects of these metabolites need further investigation. Tryptophan is known to be an important biomarker to identify human subjects at high risk for T2D since an up-regulation is already detected in patients with prediabetes. On the other hand, the anti-inflammatory vitamin nicotinic acid (NA) is down-regulated in metabolic inflammation. Nicotinuric acid (NUA), the major catabolic product of NA, showed pro-inflammatory capacity by promoting polarization of M0-macrophages in M1-macrophages. Nevertheless, there is only little knowledge about its properties and molecular mechanisms. The aim of this project is to specify the effects of NUA in metabolic inflammation and T2D

Dipeptidylpeptidase (DPP)-4 inhibitor therapy increases circulating levels of anti-inflammatory soluble frizzle receptor protein (sFRP)-5 which is decreased in severe COVID-19 disease

Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed to identify potential mechanisms for the observed DPP4i effect in COVID-19. Comparing T2D subjects with and without DPP4i treatment, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide secreted by adipose tissue macrophages acting pro-inflammatory in various diseases. We therefore examined sFRP5 levels in patients hospitalised for severe COVID-19 and found significant lower levels compared to healthy controls. Since sFRP5 might consequently be a molecular link for the beneficial effects of DPP4i in COVID-19, we further aimed to identify the exact source of sFRP5 in adipose tissue on cellular level. We therefore isolated pre-adipocytes, mature adipocytes and macrophages from adipose tissue biopsies and performed western-blotting. Results showed a sFRP5 expression specifically in mature adipocytes of subcutaneous and omental adipose tissue. In summary, our data suggest that DPP4i increase serum levels of anti-inflammatory sFRP5 which might be beneficial in COVID-19, reflecting a state of sFRP5 deficiency

Endo-PDI is required for TNFα-induced angiogenesis

Protein disulfide isomerase (PDI) and its homologs are oxidoreductases facilitating protein folding in the ER. Endo-PDI (also termed ERp46) is highly expressed in endothelial cells. It belongs to the PDI family but its physiological function is largely unknown. We studied the role of Endo-PDI in endothelial angiogenic responses. Stimulation of human umbilical vein endothelial cells (with TNFα (10 ng/ml) increased ERK1/2 phosphorylation. This effect was largely attenuated by Endo-PDI siRNA, whereas JNK and p38 MAP kinase phosphorylation was Endo-PDI independent. Similarly, TNFα-stimulated NF-κB signaling determined by IκBα degradation as well as TNFα-induced ICAM expression was unaffected by Endo-PDI siRNA. The action of Endo-PDI was not mediated by extracellular thiol exchange or cell surface PDI as demonstrated by nonpermeative inhibitors and PDI-neutralizing antibody. Moreover, exogenously added PDI failed to restore ERK1/2 activation after Endo-PDI knockdown. This suggests that Endo-PDI acts intracellularly potentially by maintaining the Ras/Raf/MEK/ERK pathway. Indeed, knockdown of Endo-PDI attenuated Ras activation measured by G-LISA and Raf phosphorylation. ERK activation influences gene expression by the transcriptional factor AP-1, which controls MMP-9 and cathepsin B, two proteases required for angiogenesis. TNFα-stimulated MMP-9 and cathepsin B induction was reduced by silencing of Endo-PDI. Accordingly, inhibition of cathepsin B or Endo-PDI siRNA blocked the TNFα-stimulated angiogenic response in the spheroid outgrowth assays. Moreover ex vivo tube formation and in vivo Matrigel angiogenesis in response to TNFα were attenuated by Endo-PDI siRNA. In conclusion, our study establishes Endo-PDI as a novel, important mediator of AP-1-driven gene expression and endothelial angiogenic function

The histone demethylase PHF8 is essential for endothelial cell migration

Epigenetic marks critically control gene expression and thus the cellular activity state. The functions of many epigenetic modifiers in the vascular system have not yet been studied. We screened for histone modifiers in endothelial cells and observed a fairly high expression of the histone plant homeodomain finger protein 8 (PHF8). Given its high expression, we hypothesize that this histone demethylase is important for endothelial cell function. Overexpression of PHF8 catalyzed the removal of methyl-groups from histone 3 lysine 9 (H3K9) and H4K20, whereas knockdown of the enzyme increased H3K9 methylation. Knockdown of PHF8 by RNAi also attenuated endothelial proliferation and survival. As a functional readout endothelial migration and tube formation was studied. PHF8 siRNA attenuated the capacity for migration and developing of capillary-like structures. Given the impact of PHF8 on cell cycle genes, endothelial E2F transcription factors were screened, which led to the identification of the gene repressor E2F4 to be controlled by PHF8. Importantly, PHF8 maintains E2F4 but not E2F1 expression in endothelial cells. Consistently, chromatin immunoprecipitation revealed that PHF8 reduces the H3K9me2 level at the E2F4 transcriptional start site, demonstrating a direct function of PHF8 in endothelial E2F4 gene regulation. Conclusion: PHF8 by controlling E2F4 expression maintains endothelial function