Unambiguous synthetic routes to sphingofungins B and F and to
their stereoisomers have been
developed based on the tin(II)-catalyzed asymmetric aldol reaction
(Chiral Lewis Acid-Controlled Synthesis
(CLAC Synthesis)). Efficient enantioselective synthesis using a
catalytic amount of a chiral source as well as
the effectiveness of this strategy for the synthesis of the
sphingofungin family have been successfully
demonstrated. Using the stereoisomers of sphingofungin B
synthesized, the relevance of its stereochemistry
to its SPT inhibitory activity has been revealed.
Spaceflight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artificial earth-gravity (artificial 1 g; AG) and microgravity (μg; MG), to investigate whether artificial 1 g exposure prevents muscle atrophy at the molecular level. Our main findings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fiber type composition but also in the alteration of gene expression profiles. In particular, transcriptome analysis suggested that AG condition could prevent the alterations of some atrophy-related genes. We further screened novel candidate genes to reveal the muscle atrophy mechanism from these gene expression profiles. We suggest the potential role of Cacng1 in the atrophy of myotubes using in vitro and in vivo gene transductions. This critical project may accelerate the elucidation of muscle atrophy mechanisms.
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