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141.
Expansion strategies for human mesenchymal stromal cells culture under xeno‐free conditions 下载免费PDF全文
Patrícia Aparecida Tozetti Samia Rigotto Caruso Amanda Mizukami Taisa Risque Fernandes Fernanda Borges da Silva Fabiola Traina Dimas Tadeu Covas Maristela Delgado Orellana Kamilla Swiech 《Biotechnology progress》2017,33(5):1358-1367
Choosing the culture system and culture medium used to produce cells are key steps toward a safe, scalable, and cost‐effective expansion bioprocess for cell therapy purposes. The use of AB human serum (AB HS) as an alternative xeno‐free supplement for mesenchymal stromal cells (MSC) cultivation has increasingly gained relevance due to safety and efficiency aspects. Here we have evaluated different scalable culture systems to produce a meaningful number of umbilical cord matrix‐derived MSC (UCM MSC) using AB HS for culture medium supplementation during expansion and cryopreservation to enable a xeno‐free bioprocess. UCM MSC were cultured in a scalable planar (compact 10‐layer flasks and roller bottles) and 3‐D microcarrier‐based culture systems (spinner flasks and stirred tank bioreactor). Ten layer flasks and roller bottles enabled the production of 2.6 ± 0.6 × 104 and 1.4 ± 0.3 × 104 cells/cm2. UCM MSC‐based microcarrier expansion in the stirred conditions has enabled the production of higher cell densities (5.5–23.0 × 104 cells/cm2) when compared to planar systems. Nevertheless, due to the moderate harvesting efficiency attained, (80% for spinner flasks and 46.6% for bioreactor) the total cell number recovered was lower than expected. Cells maintained the functional properties after expansion in all the culture systems evaluated. The cryopreservation of cells (using AB HS) was also successfully carried out. Establishing scalable xeno‐free expansion processes represents an important step toward a GMP compliant large‐scale production platform for MSC‐based clinical applications. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1358–1367, 2017 相似文献
142.
In the present paper we studied the involvement of the phosphatidylinositol-specific PLC (PI-PLC)/protein kinase C (PKC) pathway in (Na+ + K+)ATPase stimulation by heme in Leishmania amazonensis promastigotes. Heme stimulated the PKC-like activity with a concentration of 50 nM. Interestingly, the maximal stimulation of the PKC-like activity promoted by phorbol ester was of the same magnitude promoted by heme. However, the stimulatory effect of heme is completely abolished by ET-18-OCH3 and U73122, specific inhibitors of PI-PLC. (Na+ + K+)ATPase activity is increased in the presence of increased concentrations of heme, being maximally affected at 50 nM. This effect was completely reversed by 10 nM calphostin C, an inhibitor of PKC. Thus, the effect of 50 nM heme on (Na+ + K+)ATPase activity is completely abolished by ET-18-OCH3 and U73122. Taken together, these results demonstrate that the heme receptor mediates the stimulatory effect of heme on the (Na+ + K+)ATPase activity through a PI-PLC/PKC signaling pathway. 相似文献
143.
Miguel A. Rodriguez-Milla Julio Salinas 《植物生理学报》2009,(3):526-534
During the last years, our understanding of the mechanisms that control plant response to salt stress has been steadily progressing. Pharmacological studies have allowed the suggestion that the cytoskeleton may be involved in regulating such a response. Nevertheless, genetic evidence establishing that the cytoskeleton has a role in plant tolerance to salt stress has not been reported yet. Here, we have characterized Arabidopsis T-DNA mutants for genes encoding proteins orthologous to prefoldin (PFD) subunits 3 and 5 from yeast and mammals. In these organisms, PFD subunits, also known as Genes Involved in Microtubule biogenesis (GIM), form a heterohexameric PFD complex implicated in tubulin and actin folding. We show that, indeed, PFD3 and PFD5 can substitute for the loss of their yeast orthologs, as they are able to complement yeast gim2Δ and gim5Δ mutants, respectively. Our results indicate that pfd3 and pfd5 mutants have reduced levels of α- and β-tubulin compared to the wild-type plants when growing under both control and salt-stress conditions. In addition, pfd3 and pfd5 mutants display alterations in their developmental patterns and microtubule organization, and, more importantly, are hypersensitive to high concentrations of NaCl but not of LiCl or mannitol. These results demonstrate that the cytoskeleton plays an essential role in plant tolerance to salt stress. 相似文献
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María Fernanda Tapia-Armijos Jürgen Homeier Carlos Iván Espinosa Christoph Leuschner Marcelino de la Cruz 《PloS one》2015,10(9)
Deforestation and fragmentation are major components of global change; both are contributing to the rapid loss of tropical forest area with important implications for ecosystem functioning and biodiversity conservation. The forests of South Ecuador are a biological ‘hotspot’ due to their high diversity and endemism levels. We examined the deforestation and fragmentation patterns in this area of high conservation value using aerial photographs and Aster satellite scenes. The registered annual deforestation rates of 0.75% (1976–1989) and 2.86% (1989–2008) for two consecutive survey periods, the decreasing mean patch size and the increasing isolation of the forest fragments show that the area is under severe threat. Approximately 46% of South Ecuador’s original forest cover had been converted by 2008 into pastures and other anthropogenic land cover types. We found that deforestation is more intense at lower elevations (premontane evergreen forest and shrubland) and that the deforestation front currently moves in upslope direction. Improved awareness of the spatial extent, dynamics and patterns of deforestation and forest fragmentation is urgently needed in biologically diverse areas like South Ecuador. 相似文献
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Patricia Tempski Itamar S. Santos Fernanda B. Mayer Sylvia C. Enns Bruno Perotta Helena B. M. S. Paro Silmar Gannam Munique Peleias Vera Lucia Garcia Sergio Baldassin Katia B. Guimaraes Nilson R. Silva Emirene M. T. Navarro da Cruz Luis F. Tofoli Paulo S. P. Silveira Milton A. Martins 《PloS one》2015,10(6)
Context
Resilience is a capacity to face and overcome adversities, with personal transformation and growth. In medical education, it is critical to understand the determinants of a positive, developmental reaction in the face of stressful, emotionally demanding situations. We studied the association among resilience, quality of life (QoL) and educational environment perceptions in medical students.Methods
We evaluated data from a random sample of 1,350 medical students from 22 Brazilian medical schools. Information from participants included the Wagnild and Young’s resilience scale (RS-14), the Dundee Ready Educational Environment Measure (DREEM), the World Health Organization Quality of Life questionnaire – short form (WHOQOL-BREF), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI).Results
Full multiple linear regression models were adjusted for sex, age, year of medical course, presence of a BDI score ≥ 14 and STAI state or anxiety scores ≥ 50. Compared to those with very high resilience levels, individuals with very low resilience had worse QoL, measured by overall (β=-0.89; 95% confidence interval =-1.21 to -0.56) and medical-school related (β=-0.85; 95%CI=-1.25 to -0.45) QoL scores, environment (β=-6.48; 95%CI=-10.01 to -2.95), psychological (β=-22.89; 95%CI=-25.70 to -20.07), social relationships (β=-14.28; 95%CI=-19.07 to -9.49), and physical health (β=-10.74; 95%CI=-14.07 to -7.42) WHOQOL-BREF domain scores. They also had a worse educational environment perception, measured by global DREEM score (β=-31.42; 95%CI=-37.86 to -24.98), learning (β=-7.32; 95%CI=-9.23 to -5.41), teachers (β=-5.37; 95%CI=-7.16 to -3.58), academic self-perception (β=-7.33; 95%CI=-8.53 to -6.12), atmosphere (β=-8.29; 95%CI=-10.13 to -6.44) and social self-perception (β=-3.12; 95%CI=-4.11 to -2.12) DREEM domain scores. We also observed a dose-response pattern across resilience level groups for most measurements.Conclusions
Medical students with higher resilience levels had a better quality of life and a better perception of educational environment. Developing resilience may become an important strategy to minimize emotional distress and enhance medical training. 相似文献149.
Sally Hamour Poh-Yi Gan Ruth Pepper Fernanda Florez Barros Hsu-Han Wang Kim O’Sullivan Yoichiro Iwakura Terence Cook Charles Pusey Stephen Holdsworth Alan Salama 《PloS one》2015,10(8)
IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of glomerulonephritis and IL-17 deficient mice are protected from nephrotoxic nephritis. However, a regulatory role for IL-17 has recently emerged. We describe a novel protective function for IL-17 in the kidney. Bone marrow chimeras were created using wild-type and IL-17 deficient mice and nephrotoxic nephritis was induced. IL-17 deficient hosts transplanted with wild-type bone marrow had worse disease by all indices compared to wild-type to wild-type bone marrow transplants (serum urea p<0.05; glomerular thrombosis p<0.05; tubular damage p<0.01), suggesting that in wild-type mice, IL-17 production by renal cells resistant to radiation is protective. IL-17 deficient mice transplanted with wild-type bone marrow also had a comparatively altered renal phenotype, with significant differences in renal cytokines (IL-10 p<0.01; IL-1β p<0.001; IL-23 p<0.01), and macrophage phenotype (expression of mannose receptor p<0.05; inducible nitric oxide synthase p<0.001). Finally we show that renal mast cells are resistant to radiation and produce IL-17, suggesting they are potential local mediators of disease protection. This is a novel role for intrinsic cells in the kidney that are radio-resistant and produce IL-17 to mediate protection in nephrotoxic nephritis. This has clinical significance as IL-17 blockade is being trialled as a therapeutic strategy in some autoimmune diseases. 相似文献
150.
M. Fernanda Lima-Costa James Macinko Juliana Vaz de Melo Mambrini Cibele C. Cesar Sérgio V. Peixoto Wagner C. S. Magalh?es Bernardo L. Horta Mauricio Barreto Erico Castro-Costa Josélia O. A. Firmo Fernando A. Proietti Thiago Peixoto Leal Maira R. Rodrigues Alexandre Pereira Eduardo Tarazona-Santos 《PloS one》2015,10(12)