Effekte von Pro-, Prä- und Synbiotika in Bezug auf chronisch entzündliche und funktionelle Darmerkrankungen

Weder die Pathogenese der CED noch jene der funktionellen Darmer-krankungen ist heute vollständig aufgeklärt. Die Bedeutung der intestinalen Mikrobiota als Triggerfaktor mit antigenem bzw. antiinflammatorischem Potential wird in beiden Fällen diskutiert. Die Modulation der intestinalen Mikrobiota und der Darmbarriere bildet den Ansatz für die Wissenschaft der Pro-, Prä- und Synbiotika in beiden Bereichen. Im Interesse der Studien aus den Jahren 2007 bis 2010 stand in Bezug auf CED neben den Wirkungen der Probiotika an sich die Aufklärung von Wirk-mechanismen auf das Entzündungsgeschehen, wobei durchaus positive Effekte beobachtet werden konnten. In Bezug auf MC wurden für einige Stämme antiinflammatorische Effekte aufgezeigt, wenngleich Studien zur Aufrechterhaltung der Remission bei MC nur wenig erfolgreiche Resultate erbrachten. Zur Aufrechterhaltung der Remission bei CU liegen hingegen Studien zu positi-ven Effekten von E. coli Nissle 1917 vor. Um Aussagen zum Einsatz anderer Probiotika und bei aktiver CU treffen zu können, sind weitere Untersuchungen notwendig. Wenngleich sich die Datenlage zum Einsatz von Prä- und Syn-biotika bei CED noch in Grenzen hält, weisen erste Untersuchungsergebnisse doch auf positive Effekte und Erfolg versprechende Therapieansätze hin. Die Resultate zu den Effekten von Pro-, Prä- und Synbiotika bei funktionellen Darmerkrankungen sind widersprüchlich und aufgrund fehlender spezieller struktureller und biochemischer Marker, der Subjektivität der Symptom-empfindung, der Heranziehung unterschiedlicher Selektionskriterien zur Auswahl der Studienpopulation und des fehlenden Goldstandards zur Evaluierung der Effekte ungleich schwerer zu beurteilen. Dennoch existieren auch hier Hinweise auf Symptomlinderung durch einige Stämme und Substanzen.Whether the pathogenesis of inflammatory bowel diseases or functional bowel diseases are completely understood today. The explanation of the intestinal microbiota as a trigger factor with antigenic or anti-inflammatory potential is discussed in both cases. Therefore the control of the intestinal microbiota and the intestinal barrier form the background for the science of probiotics, prebiotics and synbiotics in both fields. The relevant surveys from 2007-2010 relating to inflammatory bowel disorders looked at the impact of probiotics itself, and also at the explanation of the impact mechanisms on inflammatory events. Their positive effects could be observed. Also related to Crohn`s disease, anti-inflammatory effects were shown for several strains, although surveys on maintenance of remission in patients with Crohn`s disease provided few effective results. In contrast, positive effects of maintenance of remission in patients with ulcerative colitis were shown for E. coli Nissle 1917. Further research is needed to give evidence for the effects on other strains, and also for their effectiveness on active ulcerative colitis. Even though the data for the use of pre- and synbiotics against inflammatory bowel diseases is limited, first results are encouraging. The results of the effects of pro-, pre- and synbiotics against functional bowel disorders are conflicting and much harder to assess. Missing special structural and biochemical markers, the subjectivity of symptom perception, the usage of different selection criteria for the formation of study populations, and the missing gold standard for the evaluation of the effects are all factors. Nevertheless, there is evidence for the positive effects of several strains and agents too

Ohmic heating - a novel approach for gluten-free bread baking

Gluten-free (GF) batters usually present several technological challenges that limit the performance during conventional baking and the resulting product quality. Due to the volumetric heating principle and faster heating rates, ohmic heating (OH) may be advantageous compared with conventional baking. Therefore, the potential of using ohmic heating as a novel approach for gluten-free bread baking was explored. In detail, the effect of different OH process parameters (power input, holding time) on the chemical and functional properties (specific volume, crumb firmness and relative elasticity, pore properties, color, starch gelatinization) and digestibility of breads was investigated. Results showed that GF breads could benefit from the uniform rapid heating during processing, as these breads showed superior functional properties (specific volume, 2.86-3.44 cm3/g; relative elasticity, 45.05-56.83%; porosity, 35.17-40.92%) compared with conventional oven-baked GF bread (specific volume, 2.60 cm3/g; relative elasticity, 44.23%; porosity, 37.63%). In order to maximize bread expansion and the OH performance, it was found that the OH process could be improved by applying the electrical energy in three descending power steps: first step with high power input (in this study, 2–6 kW for 15 s), followed by 1 kW for 10 s, and 0.3 kW for 1–30 min. In total, ohmic baking only needed a few minutes to obtain a fully expanded GF bread. The determination of pasting properties and starch digestibility demonstrated that these breads were comparable or even superior to GF breads baked in a conventional baking oven

Hypoxia regulates RhoA and Wnt/β-catenin signaling in a context-dependent way to control re-differentiation of chondrocytes

Cartilage tissue is avascular and hypoxic which regulates chondrocyte phenotype via stabilization of HIFs. Here, we investigated the role of hypoxia and HIFs in regulation of Rho and canonical Wnt signaling in chondrocytes. Our data demonstrates that hypoxia controls the expression of RhoA in chondrocytes in a context-dependent manner on the culturing conditions. Within a 3D microenvironment, hypoxia suppresses RhoA on which hypoxia-driven expression of chondrogenic markers depends. Conversely, hypoxia leads to upregulation of RhoA in chondrocytes on 2D with a failure in re-expression of chondrogenic markers. Similarly to RhoA, hypoxic regulation of Wnt/β-catenin signaling depends on the microenvironment. Hypoxia downregulates β-catenin within 3D hydrogels whereas it causes a potent increase on 2D. Hypoxia-induced suppression of canonical Wnt signaling in 3D contributes to the promotion of chondrogenic phenotype as induction of Wnt signaling abrogates the hypoxic re-differentiation of chondrocytes. Inhibiting Wnt/β-catenin signaling via stabilization of Axin2 leads to a synergistic enhancement of hypoxia-induced expression of chondrogenic markers. The effects of hypoxia on Rho and Wnt/β-catenin signaling are HIF-dependent as stabilizing HIFs under normoxia revealed similar effects on chondrocytes. The study reveals important insights on hypoxic signaling of chondrocytes and how hypoxia regulates cellular mechanisms depending on the cellular microenvironment

Evaluation of autoantibodies as predictors of treatment response and immune‐related adverse events during the treatment with immune checkpoint inhibitors: a prospective longitudinal pan‐cancer study

BACKGROUND: The presence of autoantibodies in the serum of cancer patients has been associated with immune‐checkpoint inhibitor (ICI) therapy response and immune‐related adverse events (irAEs). A prospective evaluation of different autoantibodies in different cancer entities is missing. MATERIALS AND METHODS: In this prospective cohort study, we included a pan‐cancer cohort of patients undergoing ICI treatment and measured a comprehensive panel of autoantibodies at treatment start and at the time point of first response evaluation. The presence and induction of autoantibodies (ANA, ENA, myositis, hepatopathy, rheumatoid arthritis) in different cancer entities were assessed and the association between autoantibodies and disease control rate (DCR), objective response rate (ORR), and progression‐free survival (PFS), as well as the development of grade 3 or higher irAEs were evaluated by logistic regression models, cox proportional hazard models, and Kaplan–Meier estimators. RESULTS: Of 44 patients with various cancer entities, neither the presence of any positive autoantibody measurement nor the presence of positive antinuclear antibodies (ANA) [≥1:80] at baseline was associated with the examined clinical endpoints (DCR, ORR, PFS) in univariable and multivariable analyses. After 8–12 weeks of ICI treatment, DCR, ORR, and PFS did not significantly differ between patients with and without any positive autoantibody measurement or positive ANA titers. The frequency of irAEs did not differ depending on autoantibody status of the patients. CONCLUSION: Autoantibodies at treatment initiation or induction after 8–12 weeks of ICI treatment are not associated with treatment efficacy as indicated by DCR, ORR, and PFS or higher grade irAEs

Patterns of peripheral blood B-cell subtypes are associated with treatment response in patients treated with immune checkpoint inhibitors: a prospective longitudinal pan-cancer study

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. METHODS: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. RESULTS: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21(-) B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p=0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p=0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p=0.039). CONCLUSION: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types

Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study.

Pan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-RBD Ig electrochemiluminescence immunoassay (ECLIA) regarding analytical, diagnostic, operational and clinical characteristics. Our work takes the form of a population-based study in the principality of Liechtenstein, including 125 cases with clinically well-described and laboratory confirmed SARS-CoV-2 infection and 1159 individuals without evidence of coronavirus disease 2019 (COVID-19). SARS-CoV-2 cases were tested for antibodies in sera taken with a median of 48 days (interquartile range, IQR, 43-52) and 139 days (IQR, 129-144) after symptom onset. Sera were also tested with other assays targeting antibodies against non-RBD-S1 and -S1/S2 epitopes. Sensitivity was 97.6% (95% confidence interval, CI, 93.2-99.1), whereas specificity was 99.8% (95% CI, 99.4-99.9). Antibody levels linearly decreased from hospitalized patients to symptomatic outpatients and SARS-CoV-2 infection without symptoms (p < 0.001). Among cases with SARS-CoV-2 infection, smokers had lower antibody levels than non-smokers (p = 0.04), and patients with fever had higher antibody levels than patients without fever (p = 0.001). Pan-SARS-CoV-2 S1-RBD Ig in SARS-CoV-2 infection cases significantly increased from first to second follow-up (p < 0.001). A substantial proportion of individuals without evidence of past SARS-CoV-2 infection displayed non-S1-RBD antibody reactivities (248/1159, i.e., 21.4%, 95% CI, 19.1-23.4). In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity with potential clinical cross-reactivity to SARS-CoV-2