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401.
Natalia N. Nalivaeva Lilia Fisk Rosa M. Canet. Aviles Svetlana A. Plesneva Igor A. Zhuravin Anthony J. Turner 《International journal of peptide research and therapeutics》2003,10(5-6):455-462
Summary In the present study we have investigated the effect of prenatal hypoxia on expression of amyloid precursor protein (APP)
and some metallopeptidases, which regulate β-amyloid peptide (Aβ) levels (neprilysin (NEP) and endothelin-converting enzyme
(ECE-1)) in the cortex of rats during different periods of postnatal development. We have found that the level of APP in the
sensorimotor cortex (SMC) of rats, analysed by Western blotting, increases from days 1 to 5 of postnatal development and then
steadily decreases with age, with the most dramatic decline in the period from day 180 to 600. In the cortex of rats subjected
to prenatal hypoxia on day 13.5 of embryogenesis, the postnatal levels of APP were higher than in the control. Secretion of
the soluble form of APP (sAPP) by α-secretase was found to be the most active on day 30 of postnatal development and there
was a significant decrease in the production of sAPP after prenatal hypoxia. NEP was found to be expressed in the cortex of
rats only at the early stages of postnatal development and it was barely detectable in adult rats. The decline of NEP levels
during ageing might contribute to accumulation of Aβ in later life in humans. Prenatal hypoxia resulted in a significant decrease
of NEP expression on day 10, but its level was recovered when animals were preconditioned to mild hypoxia. A similar phenomenon
was observed when the expression of ECE-1 was analysed. Overall, prenatal hypoxia leads to significant changes in the levels
of APP and expression of metallopeptidases involved in amyloid metabolism during all postnatal life and preconditioning to
hypoxia appeared to be neuroprotective. 相似文献
402.
Cellular hypoxic preconditioning is being employed to obtain complex, yet physiological, secretomes rich is angiogenic factors. We previously proposed exposing peripheral blood cells (PBCs) to hypoxic stress stimulation, and demonstrated that controlled release of PBC-derived factor mixtures induces directional microvessel growth in vitro. Hypoxia therefore provides a useful tool for enhancing the angiogenic potential of blood plasma, by generating compositions based on PBCs' natural responses to a wound-like microenvironment. Here, we discuss various methods for preparing and delivering Hypoxia Preconditioned Plasma (HPP), i.e., plasma derived after extracorporeal conditioning of anticoagulated blood under physiological temperature and hypoxia. Special emphasis is given to those approaches that will likely facilitate the clinical translation of HPP-based therapies. We finally draw a comparison between HPP and other, currently available blood-based products, and present the case that its arrival paves the way for developing next-generation autologous therapies toward angiogenesis-supported tissue repair and regeneration. 相似文献
403.
404.
Marta H. G. Costa Margarida S. Costa Beatriz Painho Carolina D. Sousa Inês Carrondo Enrique Oltra Beatriz Pelacho Felipe Prosper Inês A. Isidro Paula Alves Margarida Serra 《Biotechnology and bioengineering》2023,120(9):2725-2741
Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) act as signaling mediators of cellular responses. However, despite representing a promising alternative to cell-based therapies, clinical translation of EVs is currently limited by their lack of scalability and standardized bioprocessing. Herein, we integrated scalable downstream processing protocols with standardized expansion of large numbers of viable cells in stirred-tank bioreactors to improve EV production. Higher EV yields were linked to EV isolation by tangential flow filtration followed by size exclusion chromatography, rendering 5 times higher number of EVs comparatively to density gradient ultracentrifugation protocols. Additionally, when compared to static culture, EV manufacture in bioreactors resulted in 2.2 higher yields. Highlighting the role of operating under optimal cell culture conditions to maximize the number of EVs secreted per cell, MSCs cultured at lower glucose concentration favored EV secretion. While offline measurements of metabolites concentration can be performed, in this work, Raman spectroscopy was also applied to continuously track glucose levels in stirred-tank bioreactors, contributing to streamline the selection of optimal EV collection timepoints. Importantly, MSC-derived EVs retained their quality attributes and were able to stimulate angiogenesis in vitro, therefore highlighting their promising therapeutic potential. 相似文献
405.