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- Brevini, T, et al.
(författare)
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FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
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Tidskriftsartikel (refereegranskat)abstract
- Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
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- Heslop, James A., et al.
(författare)
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Concise Review : Workshop Review: Understanding and Assessing the Risks of Stem Cell-Based Therapies
- 2015
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Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:4, s. 389-400
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Forskningsöversikt (refereegranskat)abstract
- The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.
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- Sajnic, A., et al.
(författare)
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Steps in the development of an international curriculum for respiratory nurses (ICRN) : A Delphi Process plan to standardise levels of respiratory nursing education
- 2022
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Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 60:Suppl 66
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The sizable population of people with respiratory conditions places a significant demand on healthcare services and a need for specialized nursing care.Aim: The ERS Nursing Group recognized the need for harmonized curricula for respiratory nurses. The following steps incorporate the knowledge and experience of academic and clinical experts.Methodology: Steps in the Delphi Process for ICRN (Cantrill, et al. Int. J Pharm. Prac, 1996):1) 2020 - Choose Facilitator; ERS chair & 2 researchers (Sajnic A, Narsavage G, Kelly C),2) 2020 - Identify Experts; ICRN Advisory Group, in 2021, a group was added to support patient involvement,3) 2021 - Define the Problem; ICRN Global Needs Survey (Narsavage et al.) confirmed the need for ICRN and assessed the status of respiratory nursing in 25 countries worldwide,4) Review the literature; scoping review in process (2022) for a starting point for survey questions,5) Round One Questions; country-based focus groups and literature summarized by the advisory group will form survey for global group. Common items will constitute a Round Two survey,6) Round Two Questions; a survey will identify ICRN items and summarize common areas,7) Round Three Questions; what the experts are all agreed upon will be answered,8) Act on Findings; a consensus document for the core curriculum will be published.Conclusion: Worldwide recognition of respiratory nursing as a speciality with a harmonized ICRN based on the Delphi process can be effective in improving the quality of care and patients' outcomes in active partnerships with other healthcare professionals
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- Travaglini, Gabriele, et al.
(författare)
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The SAGEX review on scattering amplitudes
- 2022
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Ingår i: Journal of Physics A. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 55:44
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Forskningsöversikt (refereegranskat)abstract
- This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.
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