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Results: After incubation in medium from hypoxic cytotrophoblasts, arterial segments were more responsive to phenylephrine and to potassium-induced constriction but were less responsive to methacholine, and the vasomotor activity was increased compared with that found in vessels incubated in control medium.
Cell medium from hypoxic cells has reduced capacity to neutralize neutrophil elastase.
As a biological counterpart of these findings, conditioned medium from hypoxic CAFs promoted tube formation in HUVECs in a HIF-1α/GPER dependent manner.
In contrast to the other basal-like cell lines, conditioned medium released by MDA-MB-468 did not induce neutrophil migratory activity, and medium from hypoxic MCF-7 cells only weakly stimulated neutrophil migratory activity.
We also found that conditioned medium from hypoxic purified bridge cells attracted ECs in a cabozantinib-dependent manner, whereas SC migration was independent of VEGF signaling but still responded to other factors secreted by the bridge cells or serum.
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Conditioned medium (CM) from hypoxic cells induced migration in normoxic cells.
To test the protective effect of paracrine factors secreted by MSCs against hypoxia-induced cell death, conditioned medium from MSC hypoxic cultures was added to cardiomyocytes.
Conditioned medium from aglycemic, hypoxic and OGDR challenged brain endothelial cells (self conditioned medium from metabolically stressed brain endothelial cells) significantly induced in vitro brain endothelial capillary tube formation on matrigel compared to normal conditioned medium from brain endothelial cells.
The addition of 10 ng/mL VEGF to the hypoxic medium from GPER-silenced CAFs restored the ability to form tubule structures in HUVECs.
The aforementioned findings were quantified and recapitulated in Additional file 3. Next, we determined that the up-regulation of VEGF protein levels in hypoxic medium from CAFs is no longer evident, knocking down HIF-1α and GPER expression (Additional file 4).
These data collectively suggested that the genetic manipulation of ERBB4 induced beneficial secretome in conditioned medium, through which cardiomyocytes were protected from hypoxic stress.
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