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101.
102.
Daniela De Vita Fabiana Pandolfi Luigi Ornano Marta Feroci Isabella Chiarotto Ilaria Sileno 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):106-113
AbstractA series of N,N-dimethylcarbamates containing a N,N-dibenzylamino moiety was synthesized and tested to evaluate their ability to inhibit Acetylcholinesterase (AChE). The most active compounds 4 and 8, showed 85 and 69% of inhibition at 50?μM, respectively. Furthermore, some basic SAR rules were outlined: an alkyl linker of six methylene units is the best spacer between the carbamoyl and dibenzylamino moieties; electron-withdrawal substituents on aromatics rings of the dibenzylamino group reduce the inhibitory power. Compound 4 produces a slow onset inhibition of AChE and this is not due to the carbamoylation of the enzyme, as demonstrated by the time-dependent inhibition assay of AChE with compound 4 and by MALDI-TOF MS analysis of trypsinized AChE inhibited by compound 4. Instead, compound 4 could act as a slow-binding inhibitor of AChE, probably because of its high conformational freedom due to the linear alkyl chain. 相似文献
103.
Natália Schneider Fabiany da Costa Gon?alves Fernanda Otesbelgue Pinto Patrícia Luciana da Costa Lopez Anelise Bergmann Araújo Bianca Pfaffenseller Eduardo Pandolfi Passos Elizabeth Obino Cirne-Lima Luíse Meurer Marcelo Lazzaron Lamers Ana Helena Paz 《PloS one》2015,10(3)
Glucocorticoids and immunosuppressive drugs are commonly used to treat inflammatory disorders, such as inflammatory bowel disease (IBD), and despite a few improvements, the remission of IBD is still difficult to maintain. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have emerged as regulators of the immune response, and their viability and activation of their migratory properties are essential for successful cell therapy. However, little is known about the effects of immunosuppressant drugs used in IBD treatment on MSC behavior. The aim of this study was to evaluate MSC viability, nuclear morphometry, cell polarity, F-actin and focal adhesion kinase (FAK) distribution, and cell migratory properties in the presence of the immunosuppressive drugs azathioprine (AZA) and dexamethasone (DEX). After an initial characterization, MSCs were treated with DEX (10 μM) or AZA (1 μM) for 24 hrs or 7 days. Neither drug had an effect on cell viability or nuclear morphometry. However, AZA treatment induced a more elongated cell shape, while DEX was associated with a more rounded cell shape (P < 0.05) with a higher presence of ventral actin stress fibers (P < 0.05) and a decrease in protrusion stability. After 7 days of treatment, AZA improved the cell spatial trajectory (ST) and increased the migration speed (24.35%, P < 0.05, n = 4), while DEX impaired ST and migration speed after 24 hrs and 7 days of treatment (-28.69% and -25.37%, respectively; P < 0.05, n = 4). In conclusion, our data suggest that these immunosuppressive drugs each affect MSC morphology and migratory capacity differently, possibly impacting the success of cell therapy. 相似文献
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106.
Katie L. Cramer Mary K. Donovan Jeremy B. C. Jackson Benjamin J. Greenstein Chelsea A. Korpanty Geoffrey M. Cook John M. Pandolfi 《Ecology and evolution》2021,11(15):10098
The mass die‐off of Caribbean corals has transformed many of this region’s reefs to macroalgal‐dominated habitats since systematic monitoring began in the 1970s. Although attributed to a combination of local and global human stressors, the lack of long‐term data on Caribbean reef coral communities has prevented a clear understanding of the causes and consequences of coral declines. We integrated paleoecological, historical, and modern survey data to track the occurrence of major coral species and life‐history groups throughout the Caribbean from the prehuman period to the present. The regional loss of Acropora corals beginning by the 1960s from local human disturbances resulted in increases in the occurrence of formerly subdominant stress‐tolerant and weedy scleractinian corals and the competitive hydrozoan Millepora beginning in the 1970s and 1980s. These transformations have resulted in the homogenization of coral communities within individual countries. However, increases in stress‐tolerant and weedy corals have slowed or reversed since the 1980s and 1990s in tandem with intensified coral bleaching and disease. These patterns reveal the long history of increasingly stressful environmental conditions on Caribbean reefs that began with widespread local human disturbances and have recently culminated in the combined effects of local and global change. 相似文献
107.
Snell LM McPherson AJ Lin GH Sakaguchi S Pandolfi PP Riccardi C Watts TH 《Journal of immunology (Baltimore, Md. : 1950)》2010,185(12):7223-7234
The regulation of T cell expansion by TNFR family members plays an important role in determining the magnitude of the immune response to pathogens. As several members of the TNFR family, including glucocorticoid-induced TNFR-related protein (GITR), are found on both regulatory and effector T cells, there is much interest in understanding how their effects on these opposing arms of the immune system affect disease outcome. Whereas much work has focused on the role of GITR on regulatory T cells, little is known about its intrinsic role on effector T cells in an infectious disease context. In this study, we demonstrate that GITR signaling on CD8 T cells leads to TNFR-associated factor (TRAF) 2/5-dependent, TRAF1-independent NF-κB induction, resulting in increased Bcl-x(L). In vivo, GITR on CD8 T cells has a profound effect on CD8 T cell expansion, via effects on T cell survival. Moreover, GITR is required on CD8 T cells for enhancement of influenza-specific CD8 T cell expansion upon administration of agonistic anti-GITR Ab, DTA-1. Remarkably, CD8 T cell-intrinsic GITR is essential for mouse survival during severe, but dispensable during mild respiratory influenza infection. These studies highlight the importance of GITR as a CD8 T cell costimulator during acute viral infection, and argue that despite the similarity among several TNFR family members in inducing T lymphocyte survival, they clearly have nonredundant functions in protection from severe infection. 相似文献
108.
Elisa Ciraolo Fulvio Morello Robin M. Hobbs Frieder Wolf Romina Marone Manuela Iezzi Xiaoyun Lu Giulio Mengozzi Fiorella Altruda Giovanni Sorba Kaomei Guan Pier Paolo Pandolfi Matthias P. Wymann Emilio Hirsch 《Molecular biology of the cell》2010,21(5):704-711
Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110β is crucially needed in c-Kit–mediated spermatogonial expansion, as c-Kit–positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110β inhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers. 相似文献
109.
De Keersmaecker K Real PJ Gatta GD Palomero T Sulis ML Tosello V Van Vlierberghe P Barnes K Castillo M Sole X Hadler M Lenz J Aplan PD Kelliher M Kee BL Pandolfi PP Kappes D Gounari F Petrie H Van der Meulen J Speleman F Paietta E Racevskis J Wiernik PH Rowe JM Soulier J Avran D Cavé H Dastugue N Raimondi S Meijerink JP Cordon-Cardo C Califano A Ferrando AA 《Nature medicine》2010,16(11):1321-1327
110.
Di Pietro R Mariggiò MA Guarnieri S Sancilio S Giardinelli A Di Silvestre S Consoli A Zauli G Pandolfi A 《Journal of cellular biochemistry》2006,97(4):782-794
We have recently demonstrated that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) increases endothelial nitric oxide synthase (eNOS) phosphorylation, NOS activity, and nitric oxide (NO) synthesis in cultured human umbilical vein endothelial cells (HUVEC), without inducing apoptotic cell death. Although an important factor that regulates eNOS activity is its localization within the cells, little is known about the role of TRAIL in the regulation of eNOS trafficking among cellular compartments and the cytoskeleton involvement in this machinery. Then, we did both quantitative and semi-quantitative evaluations with biochemical assays and immune fluorescence microscopy in the presence of specific inhibitors of NOS activity as well as of cytoskeletal microtubule structures. In our cellular model, TRAIL treatment not only increased NO levels but also caused a time-dependent NO migration of fluorescent spots from the plasma membrane to the inner part of the cells. In unstimulated cells, most of the eNOS was localized at the cell membranes. However, within 10 min following addition of TRAIL, nearly all the cells showed an increased cytoplasm localization of eNOS which appeared co-localized with the Golgi apparatus at a higher extent than in unstimulated cells. These effects were associated to an increased formation of trans-cytoplasm stress fibers with no significant changes of the microtubule network. Conversely, microtubule disruption and Golgi scattering induced with Nocodazole treatment inhibited TRAIL-increased NOS activity, indicating that, on cultured HUVEC, TRAIL ability to affect NO production by regulating eNOS sub-cellular distribution is mediated by cytoskeleton and Golgi complex modifications. 相似文献