This is the institutional Repository of the Helmholtz Centre for Infection Research in Braunschweig/Germany (HZI), the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken/Germany, the TWINCORE Zentrum für Exprerimentelle und Klinische Infektionsforschung, Hannover/Germany,Helmholtz-Institut für RNA-basierte Infektionsforschung (HIRI), Braunschweig Integrated Centre for Systems biology (BRICS), Centre for Structural Systems Biology (CSSB) the Study Centre Hannover, Hannover/Germany and the Centre for Individualised Infection Medicine (CiiM).

 

  • Probiomimetics-Novel Lactobacillus-Mimicking Microparticles Show Anti-Inflammatory and Barrier-Protecting Effects in Gastrointestinal Models.

    Kuhn, Thomas; Koch, Marcus; Fuhrmann, Gregor; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Wiley, 2020-09-03)
    There is a lack of efficient therapies to treat increasingly prevalent autoimmune diseases, such as inflammatory bowel disease and celiac disease. Membrane vesicles (MVs) isolated from probiotic bacteria have shown tremendous potential for treating intestinal inflammatory diseases. However, possible dilution effects and rapid elimination in the gastrointestinal tract may impair their application. A cell‐free and anti‐inflammatory therapeutic system—probiomimetics—based on MVs of probiotic bacteria (Lactobacillus casei and Lactobacillus plantarum) coupled to the surface of microparticles is developed. The MVs are isolated and characterized for size and protein content. MV morphology is determined using cryoelectron microscopy and is reported for the first time in this study. MVs are nontoxic against macrophage‐like dTHP‐1 and enterocyte‐like Caco‐2 cell lines. Subsequently, the MVs are coupled onto the surface of microparticles according to facile aldehyde‐group functionalization to obtain probiomimetics. A significant reduction in proinflammatory TNF‐α level (by 86%) is observed with probiomimetics but not with native MVs. Moreover, it is demonstrated that probiomimetics have the ability to ameliorate inflammation‐induced loss of intestinal barrier function, indicating their potential for further development into an anti‐inflammatory formulation. These engineered simple probiomimetics that elicit striking anti‐inflammatory effects are a key step toward therapeutic MV translation.
  • Natural Products Impacting DNA Methyltransferases and Histone Deacetylases.

    Akone, Sergi Herve; Ntie-Kang, Fidele; Stuhldreier, Fabian; Ewonkem, Monique Bassomo; Noah, Alexandre Mboene; Mouelle, Simon Eitel Misse; Müller, Rolf; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Frontiers, 2020-08-13)
    Epigenetics refers to heritable changes in gene expression and chromatin structure without change in a DNA sequence. Several epigenetic modifications and respective regulators have been reported. These include DNA methylation, chromatin remodeling, histone post-translational modifications, and non-coding RNAs. Emerging evidence has revealed that epigenetic dysregulations are involved in a wide range of diseases including cancers. Therefore, the reversible nature of epigenetic modifications concerning activation or inhibition of enzymes involved could be promising targets and useful tools for the elucidation of cellular and biological phenomena. In this review, emphasis is laid on natural products that inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) making them promising candidates for the development of lead structures for anticancer-drugs targeting epigenetic modifications. However, most of the natural products targeting HDAC and/or DNMT lack isoform selectivity, which is important for determining their potential use as therapeutic agents. Nevertheless, the structures presented in this review offer the well-founded basis that screening and chemical modifications of natural products will in future provide not only leads to the identification of more specific inhibitors with fewer side effects, but also important features for the elucidation of HDAC and DNMT function with respect to cancer treatment.
  • Faecal Microbiota of Dogs Offered a Vegetarian Diet with or without the Supplementation of Feather Meal and either Cornmeal, Rye or Fermented Rye: A Preliminary Study.

    Hankel, Julia; Abd El-Wahab, Amr; Grone, Richard; Keller, Birgit; Galvez, Eric; Strowig, Till; Visscher, Christian; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-09-06)
    Anthropomorphism of dogs has affected feeding and the choice of components present in diets for dogs. Conflicting trends are present: raw or vegetarian appear more prevalent. Animal-derived proteins seem to have unfavourable impacts on intestinal microflora by decreasing the presence of Bacteroidetes. This preliminary study evaluates whether effects of diets with animal proteins on intestinal microbiota can be compensated by the addition of certain carbohydrates to dog diet. Eight female beagles were included in a cross-over study and fed a vegetarian diet or the same diet supplemented with feather meal (2.7%) and either 20% of cornmeal, fermented or non-fermented rye (moisture content of the diets about 42%). A 16S rRNA gene amplification was performed within the hypervariable region V4 on faecal samples and sequenced with the Illumina MiSeq platform. The Firmicutes/Bacteroidetes ratio tended to shift to the advantage of Firmicutes when feather meal and cornmeal were added (Firmicutes/Bacteroidetes ratio of 5.12 compared to 2.47 when offered the vegetarian diet) and tended to switch back to the advantage of Bacteroidetes if rye: fermented (2.17) or not (1.03) was added. The addition of rye might have the potential to compensate possible unfavourable effects of diets with animal proteins on intestinal microbiota of dogs.
  • CSF neurogranin as a neuronal damage marker in CJD: a comparative study with AD.

    Blennow, Kaj; Diaz-Lucena, Daniela; Zetterberg, Henrik; Villar-Pique, Anna; Karch, Andre; Vidal, Enric; Hermann, Peter; Schmitz, Matthias; Ferrer Abizanda, Isidro; Zerr, Inga; et al. (BMJ Publishing Group, 2019-05-16)
    Objective: To investigate whether cerebrospinal fluid (CSF) neurogranin concentrations are altered in sporadic Creutzfeldt-Jakob disease (CJD), comparatively with Alzheimer's disease (AD), and associated with neuronal degeneration in brain tissue. Methods: CSF neurogranin, total tau, neurofilament light (NFL) and 14-3-3 protein were measured in neurological controls (NCs, n=64), AD (n=46) and CJD (n=81). The accuracy of neurogranin discriminating the three diagnostic groups was evaluated. Correlations between neurogranin and neurodegeneration biomarkers, demographic, genetic and clinical data were assessed. Additionally, neurogranin expression in postmortem brain tissue was studied. Results: Compared with NC, CSF neurogranin concentrations were increased in CJD (4.75 times of NC; p<0.001, area under curve (AUC), 0.96 (95% CI 0.93 to 0.99) and AD (1.94 times of NC; p<0.01, AUC 0.73, 95% CI 0.62 to 0.82), and were able to differentiate CJD from AD (p<0.001, AUC 0.85, 95% CI 0.78 to 0.92). CSF tau was increased in CJD (41 times of NC) and in AD (3.1 times of NC), both at p<0.001. In CJD, neurogranin positively correlated with tau (r=0.55, p<0.001) and was higher in 14-3-3-positivity (p<0.05), but showed no association with NFL (r=0.08, p=0.46). CJD-MM1/MV1 cases displayed higher neurogranin levels than VV2 cases. Neurogranin was increased at early CJD disease stages and was a good prognostic marker of survival time in CJD. In brain tissue, neurogranin was detected in the cytoplasm, membrane and postsynaptic density fractions of neurons, with reduced levels in AD, and more significantly in CJD, where they correlated with synaptic and axonal markers. Conclusions: Neurogranin is a new biomarker of prion pathogenesis with diagnostic and prognostic abilities, which reflects the degree of neuronal damage in brain tissue in a CJD subtype manner. Keywords: alzheimer’s disease; cerebrospinal fluid; creutzfeldt-jakob disease; neurodegenerative dementias; neurofilament light; neurogranin; tau.
  • Three Planctomycetes isolated from biotic surfaces in the Mediterranean Sea and the Pacific Ocean constitute the novel species Symmachiella dynata gen. nov., sp. nov. and Symmachiella macrocystis sp. nov.

    Salbreiter, Markus; Waqqas, Muhammad; Jogler, Mareike; Kallscheuer, Nicolai; Wiegand, Sandra; Peeters, Stijn H; Heuer, Anja; Jetten, Mike S M; Boedeker, Christian; Rast, Patrick; et al. (Springer, 2020-08-24)
    Planctomycetes is a phylum of environmentally important bacteria, which also receive significant attention due to their fascinating cell biology. Access to axenic Planctomycete cultures is crucial to study cell biological features within this phylum in further detail. In this study, we characterise three novel strains, Mal52T, Pan258 and CA54T, which were isolated close to the coasts of the islands Mallorca (Spain) and Panarea (Italy), and from Monterey Bay, CA, USA. The three isolates show optimal growth at temperatures between 22 and 24 °C and at pH 7.5, divide by polar budding, lack pigmentation and form strong aggregates in liquid culture. Analysis of five phylogenetic markers suggests that the strains constitute two novel species within a novel genus in the family Planctomycetaceae. The strains Mal52T (DSM 101177T = VKM B-3432T) and Pan258 were assigned to the species Symmachiella dynata gen nov., sp. nov., while strain CA54T (DSM 104301T = VKM B-3450T) forms a separate species of the same genus, for which we propose the name Symmachiella macrocystis sp. nov.

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