Genome-wide comparison between IL-17 and combined TNF-alpha/IL-17 induced genes in primary murine hepatocytes

<p>Abstract</p> <p>Background</p> <p>Cytokines such as TNF-alpha and IL-1beta are known for their contribution to inflammatory processes in liver. In contrast, the cytokine IL-17 has not yet been assigned a role in liver diseases. IL-17 can cooperate with TNF-alpha to induce a synergistic response on several target genes in different cell lines, but no data exist for primary hepatocytes. To enhance our knowledge on the impact of IL-17 alone and combined with TNF-alpha in primary murine hepatocytes a comprehensive microarray study was designed. IL-1beta was included as this cytokine is suggested to act in a similar manner as the combination of TNF-alpha and IL-17, especially with respect to its role in mRNA stabilization.</p> <p>Results</p> <p>The present microarray analysis demonstrates that primary murine hepatocytes responded to IL-17 stimulation by upregulation of chemokines and genes, which are functionally responsible to increase and sustain inflammation. Cxcl2, Nfkbiz and Zc3h12a were strongly induced, whereas the majority of the genes were only very moderately up-regulated. Promoter analysis revealed involvement of NF-kappaB in the activation of many genes. Combined stimulation of TNF-alpha/IL-17 resulted in enhanced induction of gene expression, but significantly synergistic effects could be applied only to a few genes, such as Nfkbiz, Cxcl2, Zc3h12 and Steap4. Comparison of the gene expression profile obtained after stimulation of TNF-alpha/IL-17 versus IL-1beta proposed an "IL-1beta-like effect" of the latter cytokine combination. Moreover, evidence was provided that modulation of mRNA stability may be a major mechanism by which IL-17 regulates gene expression in primary hepatocytes. This assumption was exemplarily proven for Nfkbiz mRNA for the first time in hepatocytes. Our studies also suggest that RNA stability can partially be correlated to the existence of AU rich elements, but further mechanisms like the RNase activity of the up-regulated Zc3h12a have to be considered.</p> <p>Conclusions</p> <p>Our microarray analysis gives new insights in IL-17 induced gene expression in primary hepatocytes highlighting the crosstalk with the NF-kappaB signaling pathway. Gene expression profile suggests IL-17 alone and in concert with TNF-alpha a role in sustaining liver inflammatory processes. IL-17 might exceed this function by RNA stabilization.</p

Residential green environments are associated with human milk oligosaccharide diversity and composition

Publisher Copyright: © 2023, The Author(s).Increased exposure to greener environments has been suggested to lead to health benefits in children, but the associated mechanisms in early life, particularly via biological mediators such as altered maternal milk composition, remain largely unexplored. We investigated the associations between properties of the mother’s residential green environment, measured as (1) greenness (Normalized Difference Vegetation index, NDVI), (2) Vegetation Cover Diversity (VCDI) and (3) Naturalness Index (NI), and human milk oligosaccharides (HMOs), known for their immune- and microbiota-related health effects on the infant (N = 795 mothers). We show that HMO diversity increases and concentrations of several individual HMOs and HMO groups change with increased VCDI and NI in residential green environments. This suggests that variation in residential green environments may influence the infant via maternal milk through modified HMO composition. The results emphasize the mediating role of breastfeeding between the residential green environments and health in early life.Peer reviewe

Integrating genomics and metabolomics for scalable non-ribosomal peptide discovery.

Non-Ribosomal Peptides (NRPs) represent a biomedically important class of natural products that include a multitude of antibiotics and other clinically used drugs. NRPs are not directly encoded in the genome but are instead produced by metabolic pathways encoded by biosynthetic gene clusters (BGCs). Since the existing genome mining tools predict many putative NRPs synthesized by a given BGC, it remains unclear which of these putative NRPs are correct and how to identify post-assembly modifications of amino acids in these NRPs in a blind mode, without knowing which modifications exist in the sample. To address this challenge, here we report NRPminer, a modification-tolerant tool for NRP discovery from large (meta)genomic and mass spectrometry datasets. We show that NRPminer is able to identify many NRPs from different environments, including four previously unreported NRP families from soil-associated microbes and NRPs from human microbiota. Furthermore, in this work we demonstrate the anti-parasitic activities and the structure of two of these NRP families using direct bioactivity screening and nuclear magnetic resonance spectrometry, illustrating the power of NRPminer for discovering bioactive NRPs

project report Promise2007

Das Projekt Promise2007 befasste sich mit der Erstellung und Auswertung einer Statistik zur Mitgliedersituation im Berufsverband Medizinischer Informatiker e.V.. Mit dem Ziel mehr über die Mitglieder und ihre derzeitige Situation zu erfahren wurde das Projekt an der Fachhochschule Hannover initiiert. Statistisch erfasst wurden Fragen zum Beschäftigungsverhältnis, zu Aus- und Weiterbildung, der beruflichen Situation und persönliche Angaben. Die Ergebnisse wurden ausgewertet und daraus wichtige Erkenntnisse für den BVMI e.V. abgeleitet, welche auf die weitere Verbandsarbeit Einfluss nehmen

Optical Imaging

Optical Coherence Tomography (OCT)We describe the fundamental concept of optical coherence tomography (OCT) and discuss the two main working principles time domain OCT and frequency domain OCT. Then, we review extended functionalities including spectrally and polarization-resolved OCT as well as Doppler-OCT and show concepts for contrast enhancement. Based on these fundamentals, we demonstrate the potential of OCT for small animal imaging on the basis of exemplary studies on retinal imaging and lung imaging.Optoacoustic ImagingThis chapter deals with the fascinating topic of optoacoustic imaging, a recent powerful addition to the arsenal of in vivo functional and molecular small animal imaging. Due to its hybrid nature, involving optical excitation and ultrasonic detection, optoacoustics overcomes the imaging depth limitations of optical microscopy related to light scattering in living tissues while further benefiting from the compelling advantages of optical contrast. To this end, optoacoustic imaging has been shown capable of delivering multiple types of imaging contrast (structural, functional, kinetic, molecular) within a single imaging modality. It can further deliver images with high spatiotemporal resolution that rivals performance of other well-established whole-body imaging modalities. As such, optoacoustics can play a vital role in biomedical research, from early disease detection and monitoring of dynamic phenomena noninvasively to accelerating drug discovery.Optical ProbesThis chapter is devoted to the properties and application of fluorescence dyes as probes for optical imaging. A variety of agents have been described to date, including nontargeting dyes, vascular agents, targeted conjugates, activatable dyes, and sensing probes. The major classes encompass polymethine dyes and xanthenes dyes, both of which are commercially available in broad variations. Addressing the purpose of optical animal imaging, the most relevant parameters to apply such probes are discussed, thereby supporting the reader in choosing reasonable imaging probes and in preparing bioconjugates for his studies

Clinical features and outcome of dogs and cats with bidirectional and continuous right-to-left shunting patent ductus arteriosus

Background Studies describing the clinical progression of animals with reverse patent ductus arteriosus (PDA) are lacking. Objectives To describe the signalment, presenting signs, echocardiographic features, and survival in a group of dogs and cats with bidirectional and continuous right-to-left PDA. Animals Forty-six client-owned animals included, comprising 43 dogs and 3 cats with bidirectional or continuous right-to-left PDA. Methods Retrospective multicenter study. Medical records and echocardiographic findings reviewed from animals diagnosed with bidirectional or continuous right-to-left PDA. Impact of ductal morphology, spectral Doppler flow profile, PCV, sildenafil treatment at presentation, sildenafil dose, severity of pulmonary hypertension, general anesthesia with or without surgery and the presence of right-sided congestive heart failure (R-CHF) on crude mortality rate were evaluated via Mantel-Cox log rank comparison of Kaplan-Meier survival curves. Univariable and multivariable Cox proportional hazards analysis was performed, and hazard ratio (HR) (95% confidence intervals [CI]) was presented. Results Hindlimb collapse was the most common presenting sign in dogs (n = 16). Clinical signs in cats were variable. Median survival time was 626 days in dogs (range 1-3628 days). Dogs with R-CHF had a shorter median survival time (58 days vs 1839 days, P = .03). Dogs treated with sildenafil at initial presentation survived longer (1839 days vs 302 days, P = .03), which was the only independent predictor of survival (HR 0.35, CI 0.15-0.86, P = 0.021). Conclusions and Clinical Importance Dogs and cats with reverse PDA have a variable clinical presentation and prognosis. Survival time was longer in animals prescribed sildenafil at diagnosis. Dogs with R-CHF at presentation have a worse overall outcome

Simultaneous Multi-Harmonic Imaging of Nanoparticles in Tissues for Increased Selectivity

We investigate the use of Bismuth Ferrite (BFO) nanoparticles for tumor tissue labelling in combination with infrared multi-photon excitation at 1250 nm. We report the efficient and simultaneous generation of second and third harmonic by the nanoparticles. On this basis, we set up a novel imaging protocol based on the co-localization of the two harmonic signals and demonstrate its benefits in terms of increased selectivity against endogenous background sources in tissue samples. Finally, we discuss the use of BFO nanoparticles as mapping reference structures for correlative light-electron microscopy.Comment: 19 pages, 6 figure

Associations between human milk oligosaccharides and growth in infancy and early childhood

Background: Breastfeeding modulates infant growth and protects against the development of obesity. However, whether or not maternal variation in human milk components, such as human milk oligosaccharides (HMOs), is associated with programming of child growth remains unknown.Objective: Our objective was to determine the association between maternal HMO composition and child growth during the first 5 y of life. In addition, the association between maternal prepregnancy BMI and HMO composition was assessed.Methods: Human milk samples from 802 mothers were obtained from a prospective population-based birth cohort study, Steps to healthy development of Children (STEPS), conducted in Turku, Finland. HMO composition in these milk samples was analyzed by HPLC. Child growth data from 3 mo to 5 y were collected from municipal well-baby clinics and linked to maternal HMO composition data to test for associations.Results: Maternal HMO composition 3 mo after delivery was associated with height and weight during the first 5 y of life in children of secretor mothers. Specifically, HMO diversity and the concentration of lacto-N-neo-tetraose (LNnT) were inversely associated and that of 2'-fucosyllactose (2'FL) was directly associated with child height and weight z scores in a model adjusted for maternal prepregnancy BMI, mode of delivery, birthweight z score, sex, and time. Maternal prepregnancy BMI was associated with HMO composition.Conclusions: The association between maternal HMO composition and childhood growth may imply a causal relation, which warrants additional testing in preclinical and clinical studies, especially since 2'FL and LNnT are among the HMOs now being added to infant formula. Furthermore, altered HMO composition may mediate the impact of maternal prepregnancy BMI on childhood obesity, which warrants further investigation to establish the cause-and-effect relation.</p

Cardiac iron concentration in relation to systemic iron status and disease severity in non-ischaemic heart failure with reduced ejection fraction

Aims: Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non-advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non-advanced HFrEF and explored CI association with systemic iron status and disease severity. Methods and results: We enrolled 80 consecutive patients with non-ischaemic HFrEF with New York Heart Association class II or III symptoms and a median (interquartile range) LV ejection fraction of 25 (18–33)%. CI was 304 (262–373) μg/g dry tissue. CI was not related to immunohistological findings or the presence of cardiotropic viral genomes in EMBs and was not related to biomarkers of systemic iron status or anaemia. Patients with CI in the lowest quartile (CIQ1) had lower body mass indices and more often presented with heart failure histories longer than 6 months than patients in the upper three quartiles (CIQ2–4). CIQ1 patients had higher serum N-terminal pro-B-type natriuretic peptide levels than CIQ2–4 patients [3566 (1513–6412) vs. 1542 (526–2811) ng/L; P = 0.005]. CIQ1 patients also had greater LV end-diastolic (P = 0.001) and end-systolic diameter indices (P = 0.003) and higher LV end-diastolic pressures (P = 0.046) than CIQ2–4 patients. Conclusion: Low CI is associated with greater disease severity in patients with non-advanced non-ischaemic HFrEF. CI is unrelated to systemic iron homeostasis. The prognostic and therapeutic implications of CI measurements in EMBs should be further explored