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Moreover, different metabolic modifications are induced, such as reductions in unsaturated fatty acid contents and increases in the permeability of cell membranes, which collectively reduce plant performance (Bracale and Coraggio 2003; Tong et al. 2005; Miura and Furumoto 2013).
While prolonged stress exposure led to sodium accumulation in leaves, the concentration of soluble sodium did not increase during the early experimental timepoints (Figure S1), indicating that the immediate metabolic modifications are not caused by ion toxicity.
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Metabolic modifications were observed in the different groups when comparing the metabolic profile at time 0 and at the end of the experiment.
Since the emergence of "metabolic engineering", the potentials in producing unnatural specialty chemicals through genetic and metabolic modifications have been extensively explored, especially for the discovery of petroleum-replacing biofuels (Keasling [2012]).
Regarding the improvement of the in vivo metabolic stability, many chemical modifications are described and proved to be useful.
Besides, alteration of the cellular adaptation to hypoxia is also fundamental in cancer treatment because angiogenesis or other metabolic modifications will be stimulated to maintain tumor cell survival [ 37].
Aside from these metabolic modifications, there is evidence that the activation of AMPK by metformin may help to regulate the cell cycle via interactions with classical oncogenes and tumour suppressors.
As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.
Further modifications are almost inevitable.
Modifications aren't cheap, though.
To improve the metabolic stability, several linker modifications were attempted as replacement of amide linker along with different phenyl or other heteroaryls between C8 position of xanthine head group and terminal phenyl ring.
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