The Effective Activation of Apoptosis by AO-95 from the Aerial Part of Alpiniae officinarum in A549 Cell Line

The study was designed to examine the apoptosis inducing activity of the AO-95 from the aerial part ofAlpiniae officinarum. The AO-95 treatment to three human lung cancer cell lines （A549, NCI-H460 and NCI-H23） resulted in a dose-dependent inhibition of cell growth. The authors selected A549 cell line as a test model system. The AO-95 induced apoptosis ofA549 obviously, as shown by the results of cell cycle distribution analysis and cell apoptosis assay. Treatment of A549 with AO-95 markedly decreased the mitochondrial transmembrane potential （△ψm） suggesting AO-95-induced apoptosis may involve a mitochondrial-related pathway. Two compounds were isolated from AO-95 and their structures were identified as 3-phenylpropanal and 4-phenylbutan-2-one. Meanwhile, ten different components accounting for 98.38% of the total A0-95 composition were identified by gas chromatography-mass spectrometry. The major components were 3-phenylpropanal （33.09%） and 4-phenylbutan-2-one （51.16%）. And these two compounds showed notable cytotoxic activity with IC50 values of 14.90-78.46 μg/mL. In summary, the AO-95, dominated by phenylpropanoid constituents, shows effective apoptosis inducing activity by mitochondrial-related pathway and may be developed as an agent against human lung cancer.

PHF6 functions as a tumor suppressor by recruiting methyltransferase SUV39H1 to nucleolar region and offers a novel therapeutic target for PHF6-muntant leukemia

Mutations in the plant homeodomain-like finger protein 6(PHF6)gene are strongly associated with acute myeloid(AML)and T-cell acute lymphoblastic leukemia(T-ALL).In this study,we demonstrated that PHF6 can bind to H3K9me3 and H3K27me1 on the nucleolar chromatin and recruit histone methyltransferase SUV39H1 to the rDNA locus.The deletion of PHF6 caused a decrease in the recruitment of SUV39H1 to rDNA gene loci,resulting in a reduction in the level of H3K9me3 and the promotion of rDNA transcription.The knockdown of either SUV39H1 or PHF6 significantly attenuated the effects of increase in H3K9me3 and suppressed the transcription of rDNA induced by the overexpression of the other interacting partner,thereby establishing an interdependent relationship between PHF6 and SUV39H1 in their control of rRNA transcription.The PHF6 clinical mutants significantly impaired the ability to bind and recruit SUV39H1 to the rDNA loci,resulting in an increase in rDNA transcription activity,the proliferation of in vitro leukemia cells,and the growth of in vivo mouse xenografts.Importantly,significantly elevated levels of pre-rRNA were observed in clinical AML patients who possessed a mutated version of PHF6.The specific rDNA transcription inhibitor CX5461 significantly reduced the resistance of U937 AML cells deficient in PHF6 to cytarabine,the drug that is most commonly used to treat AML.Collectively,we revealed a novel molecular mechanism by which PHF6 recruits methyltransferase SUV39H1 to the nucleolar region in leukemia and provided a potential therapeutic target for PHF6-mutant leukemia.

Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells

Background:Tooth is vital not only for a good smile,but also good health.Yet,we lose tooth regularly due to accidents or diseases.An ideal solution to this problem is to regenerate tooth with patients’own cells.Here we describe the generation of tooth-like structures from integration-free human urine induced pluripotent stem cells(ifhU-iPSCs).Results:We first differentiated ifhU-iPSCs to epithelial sheets,which were then recombined with E14.5 mouse dental mesenchymes.Tooth-like structures were recovered from these recombinants in 3 weeks with success rate up to 30%for 8 different iPSC lines,comparable to H1 hESC.We further detected that ifhU-iPSC derived epithelial sheets differentiated into enamel-secreting ameloblasts in the tooth-like structures,possessing physical properties such as elastic modulus and hardness found in the regular human tooth.Conclusion:Our results demonstrate that ifhU-iPSCs can be used to regenerate patient specific dental tissues or even tooth for further drug screening or regenerative therapies.