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- Jaeger, Julius W., et al.
(författare)
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Microbiota modulation by dietary oat beta-glucan prevents steatotic liver disease progression
- 2024
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Ingår i: JHEP Reports. - 2589-5559. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Changes in gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) are important drivers of disease progression towards fibrosis. Therefore, reversing microbial alterations could ameliorate MASLD progression. Oat beta-glucan, a non-digestible polysaccharide, has shown promising therapeutic effects on hyperlipidemia associated with MASLD, but its impact on gut microbiota and most importantly MASLD-related fibrosis remains unknown. Methods: We performed detailed metabolic phenotyping, including assessments of body composition, glucose tolerance, and lipid metabolism, as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-induced model of MASLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiota were modulated using broad-spectrum antibiotic treatment. Results: Oat beta-glucan supplementation did not affect WSD-induced body weight gain or glucose intolerance and the metabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened MASLD-related inflammation, which was associated with significantly reduced monocyte-derived macrophage infiltration and fibroinflammatory gene expression, as well as strongly reduced fibrosis development. Mechanistically, this protective effect was not mediated by changes in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon broad-spectrum antibiotic treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in an expansion of protective taxa, including Ruminococcus, and Lactobacillus followed by reduced translocation of Toll-like receptor ligands. Conclusions: Our findings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation and fibrosis development in diet-induced MASLD. These results, along with its favorable dietary profile, suggest that it may be a cost-effective and well-tolerated approach to preventing MASLD progression and should be assessed in clinical studies. Impact and Implications: Herein, we investigated the effect of oat beta-glucan on the gut-liver axis and fibrosis development in a mouse model of metabolic dysfunction-associated steatotic liver disease (MASLD). Beta-glucan significantly reduced inflammation and fibrosis in the liver, which was associated with favorable shifts in gut microbiota that protected against bacterial translocation and activation of fibroinflammatory pathways. Together, oat beta-glucan may be a cost-effective and well-tolerated approach to prevent MASLD progression and should be assessed in clinical studies.
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| 2. |
- Sandler Topelius, Niklas, et al.
(författare)
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Automated Non-Sterile Pharmacy Compounding : A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets
- 2024
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.
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