Institution
Gdańsk Medical University
Education•Gdańsk, Poland•
About: Gdańsk Medical University is a education organization based out in Gdańsk, Poland. It is known for research contribution in the topics: Population & Cancer. The organization has 4893 authors who have published 11216 publications receiving 260523 citations.
Topics: Population, Cancer, Transplantation, Blood pressure, Breast cancer
Papers published on a yearly basis
Papers
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TL;DR: Results demonstrate leishmanolysin as a virulence factor preventing AMP‐mediated apoptotic killing of Leishmania and demonstrates the potential that AMP evasion plays during host infection by this parasite.
Abstract: Summary Human infection by the vector-borne protozoan Leishmania is responsible for substantial worldwide morbidity and mortality. The surface-metalloprotease (leishmanolysin) of Leishmania is a virulence factor which contributes to a variety of functions including evasion of complement-mediated parasite-killing and host intramacrophage survival. We tested the hypoth- esis that leishmanolysin serves to protect parasites from the cytolytic effects of various antimicrobial peptides (AMPs) which are important components of the innate immune system. We found that members of the a- and q-defensins, magainins and cathelicidins had substantially higher leishmanicidal activity against leishmanolysin-knock out mutants of L. major. Using the magainin analogue, pexiganan, as a model peptide we show that AMP evasion is due to rapid and extensive peptide degradation by wild-type parasites. Pexiganan-treatment of knock out mutants induced disruption of surface-membrane permeabil- ity and expression of features of apoptosis including smaller cell size, loss of mitochondrial membrane potential, exposure of surface phosphatidyl serine as well as induction of caspase 3/7 activity. These results demonstrate leishmanolysin as a virulence factor preventing AMP-mediated apoptotic killing. This study serves as a platform for the dissection of the AMP-mediated death pathways of Leishmania and demonstrates the potential that AMP evasion plays during host infection by this parasite.
109 citations
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TL;DR: RNA‐sequencing‐based transcriptome analysis indicated that inhibition of miRNA‐429 in HUVECs up‐regulated 209 mRNAs, a number of which regulate angiogenesis, and this regulatory network helps explain the Hif‐1 transition to HIF‐2 during chronic hypoxia in endothelial cells.
Abstract: Hypoxia-inducible factors (HIFs) 1 and 2 are dimeric α/β transcription factors that regulate cellular responses to low oxygen. HIF-1 is induced first, whereas HIF-2 is associated with chronic hypoxia. To determine how HIF1A mRNA, the inducible subunit of HIF-1, is regulated during hypoxia, we followed HIF1A mRNA levels in primary HUVECs over 24 hours using quantitative PCR. HIF1A and VEGF A (VEGFA) mRNA, a transcriptional target of HIF-1, increased ∼ 2.5- and 8-fold at 2-4 hours, respectively. To determine how the mRNAs were regulated, we identified a microRNA (miRNA), miR-429, that destabilized HIF1A message and decreased VEGFA mRNA by inhibiting HIF1A. Target protector analysis, which interferes with miRNA-mRNA complex formation, confirmed that miR-429 targeted HIF1A message. Desferoxamine treatment, which inhibits the hydroxylases that promote HIF-1α protein degradation, stabilized HIF-1 activity during normoxic conditions and elevated miR-429 levels, demonstrating that HIF-1 promotes miR-429 expression. RNA-sequencing-based transcriptome analysis indicated that inhibition of miRNA-429 in HUVECs up-regulated 209 mRNAs, a number of which regulate angiogenesis. The results demonstrate that HIF-1 is in a negative regulatory loop with miR-429, that miR-429 attenuates HIF-1 activity by decreasing HIF1A message during the early stages of hypoxia before HIF-2 is activated, and this regulatory network helps explain the HIF-1 transition to HIF-2 during chronic hypoxia in endothelial cells.
108 citations
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TL;DR: The nanotoxicity of amorphous 10SiO₂-NP on submucosal cells is associated with inflammation, the release of ROS leading to apoptosis, and decreased cell survival.
Abstract: There is growing evidence that amorphous silica nanoparticles (SiO₂-NP) can cause an inflammatory response in the lung. We studied in vitro the effects of exposing human lung submucosal cells to SiO₂-NP of various sizes (10, 150, and 500 nm) for 2-24 h. Cell survival, reactive oxygen species (ROS), malondialdehyde (MDA) levels, cytokine production, inflammatory gene expression, and genotoxicity were measured after exposure of Calu-3 cells to 10SiO₂-NP in the presence or absence of the flavanoid fisetin and an antioxidant enzyme catalase. The exposure of Calu-3 cells to 10SiO₂-NP resulted in (1) increased cytotoxicity and cell death in a time- and concentration-dependent manner, with a lethal concentration (LC₅₀) of 9.7 μg/mL after 24 h; (2) enhanced gene expression of interleukin (IL)-6, IL-8, and matrix metalloproteinase-9; (3) a significant correlation between increases in MDA and cytotoxicity at 18 h; (4) ROS production; (5) IL-6 and IL-8 release; and (6) up-regulation of the pro-apoptotic genes, p53 and caspase-3. Cell death and inflammatory reactions were attenuated by fisetin and catalase. We observed that 150- and 500SiO₂-NP exerted no toxic effects on Calu-3 cells. In conclusion, the nanotoxicity of amorphous 10SiO₂-NP on submucosal cells is associated with inflammation, the release of ROS leading to apoptosis, and decreased cell survival. The nanotoxic effects of 10SiO₂-NP can be decreased by fisetin and catalase treatment, implicating oxidative stress in this injury.
108 citations
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Université de Montréal1, Max Planck Society2, University of Barcelona3, University of Greifswald4, Swiss Institute of Bioinformatics5, Gdańsk Medical University6, University College London7, University of Vienna8, Okinawa Institute of Science and Technology9, Hiroshima University10, University of Tsukuba11, Queen Mary University of London12, École Normale Supérieure13, University of Mainz14, Science for Life Laboratory15, Emory University16, University of Paris17
TL;DR: A large and informative dataset is assembled to address the difficulty resolving the problem of whether the phylogenetic signal supporting the correct solution is weak and affected by inadequate modeling, creating a misleading non-phylogenetic signal, and concludes that the Xenacoelomorpha are simplified relatives of the Ambulacraria.
108 citations
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TL;DR: In patients with ECOG PS 2, nivolumab had similar tolerability, but outcomes were worse, as expected in this difficult-to-treat, poor prognosis population, with OS outcomes consistent with phase 3 data.
108 citations
Authors
Showing all 4927 results
Name | H-index | Papers | Citations |
---|---|---|---|
Magdi H. Yacoub | 109 | 1267 | 52431 |
Virend K. Somers | 106 | 615 | 54203 |
Felix Mitelman | 95 | 578 | 35416 |
Andrzej Slominski | 91 | 469 | 27900 |
Nils Mandahl | 86 | 427 | 25006 |
Fredrik Mertens | 84 | 406 | 28705 |
Enriqueta Felip | 83 | 622 | 53364 |
Pieter E. Postmus | 81 | 384 | 24039 |
Wilhelm Kriz | 73 | 222 | 19335 |
Godefridus J. Peters | 73 | 523 | 28315 |
Jacek Jassem | 73 | 602 | 35976 |
Piotr Rutkowski | 72 | 563 | 42218 |
Thomas Frodl | 70 | 258 | 16469 |
Eric J. Velazquez | 70 | 396 | 27539 |
Argye E. Hillis | 68 | 398 | 22230 |