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S6K1 Plays a Critical Role in Early Adipocyte Differentiation
Carnevalli, Larissa S.,Masuda, Kouhei,Frigerio, Francesca,Le Bacquer, Olivier,Um, Sung Hee,Gandin, Valentina,Topisirovic, Ivan,Sonenberg, Nahum,Thomas, George,Kozma, Sara C. Elsevier 2010 Developmental cell Vol.18 No.5
<P><B>Summary</B></P><P>Earlier, we reported that <I>S6K1</I><SUP>−/−</SUP> mice have reduced body fat mass, have elevated rates of lipolysis, have severely decreased adipocyte size, and are resistant to high fat diet (HFD)-induced obesity. Here we report that adipocytes of <I>S6K1</I><SUP>−/−</SUP> mice on a HFD have the capacity to increase in size to a degree comparable to that of wild-type (WT) mice, but not in number, indicating an unexpected lesion in adipogenesis. Tracing this lesion revealed that S6K1 is dispensable for terminal adipocyte differentiation, but is involved in the commitment of embryonic stem cells to early adipocyte progenitors. We further show that absence of S6K1 attenuates the upregulation of transcription factors critical for commitment to adipogenesis. These results led to the conclusion that a lack of S6K1 impairs the generation of de novo adipocytes when mice are challenged with a HFD, consistent with a reduction in early adipocyte progenitors.</P> <P><B>Graphical Abstract</B></P><P><ce:figure></ce:figure></P>
New tricyclic systems as photosensitizers towards triple negative breast cancer cells
Marilia Barreca,Angela Maria Ingarra,Maria Valeria Raimondi,Virginia Spanò,Antonio Palumbo Piccionello,Michele De Franco,Luca Menilli,Valentina Gandin,Giorgia Miolo,Paola Barraja,Alessandra Montalbano 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.11
Nineteen pyrrolo[1,2- h ][1,7]naphthyridinonesand pyrido[2,3- c ]pyrrolo[1,2- a ]azepinones were synthesizedas new tricyclic systems in which the pyridine ringis annelated to the 6,7-dihydroindolizin-8(5 H )-one and5,6,7,8-tetrahydro-9 H -pyrrole[1,2- a ]azepine-9-one moietiesto obtain potential photosensitizing agents. They were testedfor their photoantiproliferative activity on a triple-negativebreast cancer cell line, MDA-MB-231, in the dark and underUVA light (2.0 J/cm 2 ). We demonstrated that their toxicity,only when exposed to light, was primarily due to the generationof reactive oxygen species while their photodegradationproducts were not responsible for their activity. The mostactive compounds exhibited photocytotoxicity with IC 50 valuesat low micromolar level inducing a decrease in the intracellularcontent of thiol, thus triggering cancer cell deaththrough apoptosis. All the pyridone derivatives revealed tobe pure photosensitizers with preferential photocytotoxicactivity towards cancerous over healthy cells. Altogether,the results obtained confi rm pyrrolo[1,2- h ][1,7]naphthyridinonesand pyrido[2,3- c ]pyrrolo[1,2- a ]azepinones as promisingphotosensitisers against triple-negative breast cancer.