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FOXO3 (or FOXO3a) is a member of the forkhead box class O (FOXO) transcription factors which have been shown to play critical roles in modulating a number of cellular processes, such as metabolism, differentiation, and transformation in animal cells [1] [7].
Inhibition of TOR signaling leads to extended longevity in both invertebrate and invertebrate species by modulating a number of downstream molecular pathways [ 1, 2].
It appears to act by modulating a number of cellular adhesion molecules, for example β1-integrin, and thus regulates the interactions between these molecules and other cellular and extracellular matrix proteins involved in the process of adhesion [ 26- 28].
It appears that coagulants, serine proteases, and matrix metalloproteases (MMPs) facilitate tumor cell metastasis by modulating a number of host vascular cell responses as well as by acting directly on tumor cells themselves.
MicroRNA (miRNA), a class of newly emerging small noncoding RNAs, has been demonstrated to serve as a vital player in modulating a number of biological activities ranging from embryogenesis to programmed cell death as well as the maintenance of HSCs.
The activation of these two signalling pathways rewires malignant cells to acquire an anabolic phenotype to promote anabolism by multiple actions which include direct phosphorylation and regulation of metabolic enzymes, activating and inactivating transcription factors that regulate metabolism as well as modulating a number of regulatory kinases [ 2].
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Epidermal growth factor (EGF) is a peptide known to modulate a number of cellular responses including embryogenesis, cell proliferation, and cell survival.
Antioxidants are known to exert beneficial effects in ameliorating the injurious effects of hyperglycaemia in different in vitro and in vivo models [2] and the intake of natural antioxidants, like polyphenols, is able to modulate a number of chronic inflammatory diseases including type 2 diabetes [3].
Besides its ability to inhibit the core apoptotic machinery, Bcl-xL has been shown to modulate a number of other aspects of cellular physiology.
Increased expression of Bcl-xL in cancer has been shown to confer resistance to a broad range of apoptotic stimuli and to modulate a number of other aspects of cellular physiology, including energy metabolism, cell cycle, autophagy, mitochondrial fission/fusion and cellular adhesion.
The dose of PBT2 was chosen based upon our own historical data, where we have shown that this level of exposure to the compound effectively modulates a number of biochemical and behavioural parameters in various transgenic mouse models of AD, but does not alter bulk brain metal levels [10].
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