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- Abbasi-Dokht, T, et al.
(författare)
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Multistrain Probiotics Supplement Alleviates Asthma Symptoms via Increasing Treg Cells Population: A Randomized, Double-Blind, Placebo-Controlled Trial
- 2023
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 184:3, s. 291-301
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The favorable effects of probiotics have been demonstrated in allergic disorders. However, the underlying immunological mechanisms are poorly understood. In the present study, we investigated the improvement of clinical symptoms and immunological balance after receiving probiotics in patients with asthma. <b><i>Methods:</i></b> The present study was a randomized, double-blind, placebo-controlled trial in which 40 patients with asthma were enrolled. They were treated with probiotics or placebo: 1 capsule/day for 8 weeks. Pulmonary function test, percentage of CD4<sup>+</sup> CD25<sup>+</sup> FoxP3<sup>+</sup> Tregs, and gene expression of T-bet, GATA-3, RORγt, and Foxp3 in PBMCs were assessed at baseline and after treatment. <b><i>Results:</i></b> Our results showed a significant increase in the expression of FoxP3 and CD4<sup>+</sup> CD25<sup>+</sup> FoxP3<sup>+</sup> Tregs population, while RORγt and GATA3 expression were reduced. In addition, pulmonary function tests showed a significant improvement in forced expiratory volume and forced vital capacity after receiving probiotics. <b><i>Discussion/Conclusion:</i></b> Our findings demonstrate that 8-week treatment with probiotic supplementation can control T-helper 2-predominant and Th17 pro-inflammatory responses and improve forced vital and forced expiratory volume in asthmatic patients. It seems probiotics can be used besides common treatments for patients with asthma.
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- Ben-Akiva, Elana, et al.
(författare)
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Biodegradable lipophilic polymeric mRNA nanoparticles for ligand-free targeting of splenic dendritic cells for cancer vaccination
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:26
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticle (NP) -based mRNA cancer vaccines hold great promise to realize person-alized cancer treatments. To advance this technology requires delivery formulations for efficient intracellular delivery to antigen-presenting cells. We developed a class of bioreducible lipophilic poly(beta- amino ester) nanocarriers with quadpolymer architec-ture. The platform is agnostic to the mRNA sequence, with one -step self-assembly allow-ing for delivery of multiple antigen-encoding mRNAs as well as codelivery of nucleic acid-based adjuvants. We examined structure-function relationships for NP-mediated mRNA delivery to dendritic cells (DCs) and identified that a lipid subunit of the pol-ymer structure was critical. Following intravenous administration, the engineered NP design facilitated targeted delivery to the spleen and preferential transfection of DCs without the need for surface functionalization with targeting ligands. Treatment with engineered NPs codelivering antigen-encoding mRNA and toll -like receptor agonist adjuvants led to robust antigen-specific CD8+ T cell responses, resulting in efficient antitumor therapy in in vivo models of murine melanoma and colon adenocarcinoma.
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- Karlsson, Johan, 1979-, et al.
(författare)
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Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy
- 2021
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Ingår i: Advanced Functional Materials. - : John Wiley & Sons. - 1616-301X .- 1616-3028. ; 31:17
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Tidskriftsartikel (refereegranskat)abstract
- Clinical translation of polymer-based nanocarriers for systemic delivery of RNA has been limited due to poor colloidal stability in the blood stream and intracellular delivery of the RNA to the cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking of bioreducible nanoparticles for improved stability extracellularly and rapid release of RNA intracellularly. In this design, the polymeric nanocarriers contain ester bonds for hydrolytic degradation and disulfide bonds for environmentally triggered small interfering RNA (siRNA) release in the cytosol. These photocrosslinked bioreducible nanoparticles (XbNPs) have a shielded surface charge, reduced adsorption of serum proteins, and enable superior siRNA-mediated knockdown in both glioma and melanoma cells in high-serum conditions compared to non-crosslinked formulations. Mechanistically, XbNPs promote cellular uptake and the presence of secondary and tertiary amines enables efficient endosomal escape. Following systemic administration, XbNPs facilitate targeting of cancer cells and tissue-mediated siRNA delivery beyond the liver, unlike conventional nanoparticle-based delivery. These attributes of XbNPs facilitate robust siRNA-mediated knockdown in vivo in melanoma tumors colonized in the lungs following systemic administration. Thus, biodegradable polymeric nanoparticles, via photocrosslinking, demonstrate extended colloidal stability and efficient delivery of RNA therapeutics under physiological conditions, and thereby potentially advance systemic delivery technologies for nucleic acid-based therapeutics.
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