Watanabe, Ayaka Tanaka, Hiroki Sakurai, Yu Tange, Kota Nakai, Yuta Ohkawara, Tatsuya Takeda, Hiroshi Harashima, Hideyoshi Akita, Hidetaka
Hokkaido Univ Fac Pharmaceut Sci Lab Mol Design Pharmaceut Kita Ku Kita12 Nishi6 Sapporo Hokkaido 0600812 JapanHokkaido Univ Fac Pharmaceut Sci Lab Innovat Nanomed Kita Ku Kita12 Nishi6 Sapporo Hokkaido 0600812 JapanNOF Corp Kawasaki Ku 3-3 Chidori Cho Kawasaki Kanagawa 2100865 JapanHokkaido Univ Fac Pharmaceut Sci Lab Pathophysiol & Therapeut Kita Ku Kita12 Nishi6 Sapporo Hokkaido 0600812 JapanChiba Univ Grad Sch Pharmaceut Sci Chuo Ku 1-8-1 Inohana Chiba Chiba 2608675 Japan
摘要:
Taking advantage of the enhanced permeation and retention (EPR) effect is a promising approach for delivering macromolecules or nanoparticles to tumors. Recent studies revealed that this strategy is also applicable for targeting other pathological lesions (i.e. inflammatory disease). In the present study, we report the optimal size of a nanoparticle for allowing the higher accumulation of a particle in an inflammatory lesion using a dextran sulfate sodium (DSS)-induced colitis model. As a nanoparticle platform, we utilized a SS-cleavable and pH-activated lipid-like material (ssPalm), that can be used to produce particles in a variety of sizes ranging from 50 nm to 180 nm while using the same lipid composition. In healthy mice, particle accumulation remained low regardless of size. In contrast, the accumulation in inflammatory colon tissue was enhanced depending on the progress of the inflammation. In this situation, the apparent uptake clearance accumulation of a mid-sized particle (113 nm on average) was higher than that for smaller and larger (54 nm and 183 nm in average, respectively) ones. Therefore, controlling particle size is an important parameter for the extensive targeting of inflammatory lesion. (C) 2016 Elsevier B.V. All rights reserved.
摘要:
Background and Aims Probiotic properties of Enterococcus strains have been reported previously. In this study, we investigated the effects of Enterococcus (E.) durans TN-3 on the development of dextran sulfate sodium (DSS) colitis. Methods BALB/c mice were fed with 4.0% DSS in normal chow. Administration of TN-3 (10mg/day) was initiated 7days before the start of DSS feeding. Mucosal cytokine expression was analyzed by real time-PCR and immunohistochemistry. The lymphocyte subpopulation were analyzed by flow cytometry. The gut microbiota profile was analyzed by a terminal-restriction fragment length polymorphism method (T-RFLP). Results The disease activity index and histological colitis score were significantly lower in the DSS plus TN-3 group than in the DSS group. The mucosal mRNA expression of proinflammatory cytokines (IL-1 beta, IL-6, IL-17A and IFN-gamma) decreased significantly in the DSS plus TN-3 group as compared to the DSS group. The proportion of regulatory T cells (Treg cells) in the mucosa increased significantly in the DSS plus TN-3 group as compared to the DSS group. Both fecal butyrate levels and the diversity of fecal microbial community were significantly higher in the TN-3 plus DSS group than in the DSS group. Conclusions E. durans TN-3 exerted an inhibitory effect on the development of DSS colitis. This action might be mediated by the induction of Treg cells and the restoration of the diversity of the gut microbiota.
Ghisi, Margherita Kats, Lev Masson, Frederick Li, Jason Kratina, Tobias Vidacs, Eva Gilan, Omer Doyle, Maria A. Newbold, Andrea Bolden, Jessica E. Fairfax, Kirsten A. de Graaf, Carolyn A. Firth, Matthew Zuber, Johannes Dickins, Ross A. Corcoran, Lynn M. Dawson, Mark A. Belz, Gabrielle T. Johnstone, Ricky W.
Peter MacCallum Canc Ctr Canc Therapeut Program St Andrews Pl East Melbourne Vic 3002 AustraliaMonash Univ Australian Ctr Blood Dis Melbourne Vic 3004 AustraliaUniv Melbourne Sir Peter MacCallum Dept Oncol Parkville Vic 3010 AustraliaOlivia Newton John Canc Res Inst Canc Inflammat Lab Heidelberg Vic 3084 AustraliaLa Trobe Univ Sch Canc Med Heidelberg Vic 3084 AustraliaWalter & Eliza Hall Inst Med Res Mol Immunol Div Parkville Vic 3052 AustraliaUniv Melbourne Dept Med Biol Parkville Vic 3010 AustraliaPeter MacCallum Canc Ctr Bioinformat Core St Andrews Pl East Melbourne Vic 3002 AustraliaPeter MacCallum Canc Ctr Res Comp Facil St Andrews Pl East Melbourne Vic 3002 AustraliaWalter & Eliza Hall Inst Med Res Mol Med Div 1G Royal Parade Parkville Vic 3052 AustraliaVienna Bioctr VBC Res Inst Mol Pathol IMP Dr Bohr Gasse 7 A-1030 Vienna Austria
摘要:
E proteins and their antagonists, the Id proteins, are transcriptional regulators important for normal hematopoiesis. We found that Id2 acts as a key regulator of leukemia stem cell (LSC) potential in MLL-rearranged acute myeloid leukemia (AML). Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth. Importantly, MLL-AF9 itself controls the E-protein pathway by suppressing Id2 while directly activating E2-2 expression, and E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells. Remarkably, Id2 tumor-suppressive function is conserved in t(8;21) AML. Low expression of Id2 and its associated gene signature are associated with poor prognosis in MLL-rearranged and t(8;21) AML patients, identifying the Id2/E-protein axis as a promising new therapeutic target in AML.
摘要:
3D concrete printing as an additive manufacturing method can bring a revolution to the construction industry by increasing sustainability, efficiency, and safety. Concrete printing is a complex process influenced by numerous parameters from different disciplines and stages of design and construction. Among them, process parameters have a great role in defining the final product quality, and there are least known about their interrelations and effect on process and product quality criteria. A printed layer dimensional performance is chosen to be studied in order to increase stability, precision and compliant with requirements, in addition, to proposing a methodology to investigate the effect of process parameters on final product quality of concrete printing process. The design of Experiment methodology is employed to derive empirical models and be used as the core of developed Decision Support Systems. dimensional Decision Support System (dDSS) is developed to assists decision makers' decision regarding process parameters to reach defined dimensional performance, and improve concrete printing g process and product. Decisions in both managerial and technical level can benefit from dDSS, increase the traceability of concrete printing process by technical decision makers and also managers.