Three new pyrrole alkaloids from the endophytic fungus Albifimbria viridis

Three new pyrrole alkaloids albifipyrrols A-C(1-3),were isolated from the endophytic fungus Albifimbria viridis col-lected from the Chinese medicinal plant.Their structures were elucidated by extensive NMR and HRESIMS spectro-metric analyses.All compounds were evaluated for immunosuppressive activity.Fortunately,compound 2 exhibits certain inhibition specifically against the LPS-induced proliferation of B lymphocyte cells with IC50 value 16.16μM.

A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma

Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

RNA-binding motif protein RBM47 promotes tumorigenesis in nasopharyngeal carcinoma through multiple pathways

RNA binding motif proteins(RBMs)have been widely implicated in the tumorigenesis of multiple human cancers but scarcely studied in nasopharyngeal carcinoma(NPC).Here,we compare the m RNA levels of 29 RBMs between 87 NPC and 10 control samples.We find that RBM47 is frequently upregulated in NPC specimens,and its high expression is associated with the poor prognosis of patients with NPC.Biological experiments show that RBM47 plays an oncogenic role in NPC cells.Mechanically,RBM47 binds to the promoter and regulates the transcription of BCAT1,and its overexpression partially rescues the inhibitory effects of RBM47-knockdown on NPC cells.Moreover,transcriptome analysis reveals that RBM47 regulates alternative splicing of pre-m RNA,including those cancer-related,to a large extent in NPC cells.Furthermore,RBM47 binds to hnRNPM and cooperatively regulates multiple splicing events in NPC cells.In addition,we find that knockdown of hnRNPM inhibits proliferation and migration of NPC cells.Our study,taken together,shows that RBM47 promotes the progression of NPC through multiple pathways,acting as a transcriptional factor and a modulator of alternative splicing in cooperation with hnRNPM.Our study also highlights that RBM47 and hnRNPM could be prognostic factors and potential therapeutic targets for NPC.