Search results for "LK"
showing 10 items of 8438 documents
Direct estrogen receptor (ER) / HER family crosstalk mediating sensitivity to lumretuzumab and pertuzumab in ER+ breast cancer.
2017
Bidirectional cross talk between members of the human epidermal growth factor family of receptors (HER) and the estrogen receptor (ER) is believed to underlie resistance mechanisms that develop in response to treatment with anti-HER agents and endocrine therapy. We investigated the interaction between HER2, HER3 and the ER in vitro using human embryonic kidney cells transfected with human HER2, HER3, and ERα. We also investigated the additive efficacy of combination regimens consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine (fulvestrant) therapy in vivo. Our data show that both HER2 and HER3 can directly complex with the ER and can mediate phosphorylation of the …
Alkaline phosphatase dual-binding sites for collagen dictate cell migration and microvessel assembly in vitro
2020
Interactions between cell types, growth factors, and extracellular matrix components involved in angiogenesis are crucial for new vessel formation leading to tissue regeneration. This study investigated whether cocultures of fibroblasts and endothelial cells (ECs; from macro- or microvasculature) play a role in the formation of microvessel-like structures by ECs, as well as modulate fibroblast differentiation and growth factors production (vascular endothelial cell growth factor, basic fibroblast growth factor, active transforming growth factor-beta 1, and interleukin-8), which are important for vessel sprouting and maturation. Data obtained revealed that in vitro coculture systems of fibro…
Mast cells crosstalk with B cells in the gut and sustain IgA response in the inflamed intestine.
2021
B lymphocytes are among the cell types whose effector functions are modulated by mast cells (MCs). The B/MC crosstalk emerged in several pathological settings, notably the colon of inflammatory bowel disease (IBD) patients is a privileged site in which MCs and IgA+ cells physically interact. Herein, by inducing conditional depletion of MCs in red MC and basophil (RMB) mice, we show that MCs control B cell distribution in the gut and IgA serum levels. Moreover, in dextran sulfate sodium (DSS)-treated RMB mice, the presence of MCs is fundamental for the enlargement of the IgA+ population in the bowel and the increase of systemic IgA production. Since both conventional B-2 and peritoneal-deriv…
Mast cells within cellular networks
2018
Mast cells are highly versatile in terms of their mode of activation by a host of stimuli and their ability to flexibly release a plethora of biologically highly active mediators. Within the immune system, mast cells can best be designated as an active nexus interlinking innate and adaptive immunity. Here we try to draw an arc from initiation of acute inflammatory reactions to microbial pathogens to development of adaptive immunity and allergies. This multifaceted nature of mast cells is made possible by interaction with multiple cell types of immunologic and nonimmunologic origin. Examples for the former include neutrophils, eosinophils, T cells, and professional antigen-presenting cells. …
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem ce…
2016
AbstractHutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process an…
Effect of lemon leaves on energy and C–N balances, methane emission, and milk performance in Murciano-Granadina dairy goats
2018
[EN] The objective of this experiment was to find out the effect of lemon leaves on energy and C-N balances, methane emission, and milk performance in dairy goats. Lemon leaves were used to replace alfalfa as forage in a diet for Murciano-Granadina goats. Ten Murciano-Granadina dairy goats (44.1 +/- 4.47 kg of BW) in late lactation (185 +/- 7.2 d) were selected in a crossover design experiment, where each goat received 2 treatments in 2 periods. One group was fed a mixed ration with 450 g of pelleted alfalfa per kilogram of DM (ALF diet) and, the other group replaced alfalfa with 450 g of pelleted lemon leaves per kilogram DM (LEM diet). The concentrate was pelleted, being the same for the …
Hyperosmolarity and Benzalkonium Chloride Differently Stimulate Inflammatory Markers in Conjunctiva-Derived Epithelial Cells in vitro
2017
Tear hyperosmolarity is known to cause ocular surface inflammation in dry eye syndrome. Benzalkonium chloride (BAK), an eyedrop preservative, is known to induce dry eye in long-term-treated patients. Analyzing the modulation of the proinflammatory potential of hyperosmolarity in the presence of BAK on the conjunctiva could give new insights into the effect of this preservative on the disease. In a hyperosmolar model on a conjunctiva-derived cell line, and in the presence of BAK, we evaluated key inflammatory markers [CCL2, IL-8, IL-6, macrophage migration inhibitory factor (MIF) and intercellular adhesion molecule (ICAM)-1] as well as the osmoprotectant element nuclear factor of activated T…
Alkyne-Functionalized Coumarin Compound for Analytic and Preparative 4-Thiouridine Labeling
2017
Bioconjugation of RNA is a dynamic field recently reinvigorated by a surge in research on post-transcriptional modification. This work focuses on the bioconjugation of 4-thiouridine, a nucleoside that occurs as a post-transcriptional modification in bacterial RNA and is used as a metabolic label and for cross-linking purposes in eukaryotic RNA. A newly designed coumarin compound named 4-bromomethyl-7-propargyloxycoumarin (PBC) is introduced, which exhibits remarkable selectivity for 4-thiouridine. Bearing a terminal alkyne group, it is conductive to secondary bioconjugation via “click chemistry”, thereby offering a wide range of preparative and analytical options. We applied PBC to quantita…
Production of High Amounts of Hepatotoxin Nodularin and New Protease Inhibitors Pseudospumigins by the Brazilian Benthic Nostoc sp. CENA543
2017
Nostoc is a cyanobacterial genus, common in soils and a prolific producer of natural products. This research project aimed to explore and characterize Brazilian cyanobacteria for new bioactive compounds. Here we report the production of hepatotoxins and new protease inhibitors from benthic Nostoc sp. CENA543 isolated from a small, shallow, saline-alkaline lake in the Nhecolandia, Pantanal wetland area in Brazil. Nostoc sp. CENA543 produces exceptionally high amounts of nodularin-R. This is the first free-living Nostoc that produces nodularin at comparable levels as the toxic, bloom-forming, Nodularia spumigena. We also characterized pseudospumigins A-F, which are a novel family of linear te…
Mitophagy in human astrocytes treated with the antiretroviral drug Efavirenz: Lack of evidence or evidence of the lack
2019
Efavirenz (EFV), a first generation non-nucleoside analogue reverse transcriptase inhibitor widely employed in combination antiretroviral therapy regimens over the last 20 years, has been associated with a wide range of neuropsychiatric effects and has also been linked with HIV-associated neurocognitive disorder (HAND). EFV has been reported to alter mitochondrial dysfunction and bioenergetics in different cell types, including astrocytes. Here, we analyzed whether this mitochondrial effect is associated with alterations in autophagy and, more specifically, mitophagy. U251-MG cells were exposed to EFV (10 and 25 μM; 24 h) and the effect was compared with that of CCCP - an uncoupler of the m…