microRNA-378b regulates ethanol-induced hepatic steatosis by targeting CaMKK2 to mediate lipid metabolism.

Alcoholic liver disease (ALD) has seriously harmed the health of people worldwide, but its underlying mechanisms remain unclear. This study aims to clarify the biological function of microRNA-378b (miR-378b) in ethanol (EtOH)-induced hepatic lipid accumulation. Here, we report miR-378b is over-expressed in EtOH-induced cells and EtOH-fed mice and finally accelerates lipid accumulation. MiR-378b directly targets Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a kinase of AMP-activated protein kinase (AMPK), and mediates the protein level of CaMKK2. Over-expression of miR-378b exacerbated the lipid accumulation induced by EtOH and inhibited CaMKK2 and the AMPK cascade while inhibition of miR-378b ameliorated lipid metabolism dysfunction in vivo and in vitro. In brief, our results show that miR-378b plays an important role in the regulation of lipid metabolism by directly targeting CaMKK2.

A Real-Time Fluorescent Reverse Transcription Quantitative PCR Assay for Rapid Detection of Genetic Markers' Expression Associated with Fusarium Wilt of Banana Biocontrol Activities in Bacillus.

Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), especially Tropical Race 4 (TR4), seriously threatens banana production worldwide. There is no single effective control measure, although certain Bacillus strains secrete antibiotics as promising disease-biocontrol agents. This study identified five Bacillus strains displaying strong antibiotic activity against TR4, using a systemic assessment for presence/absence of genetic markers at genome level, and expression profiles at transcriptome level. A conventional PCR with 13 specific primer pairs detected biocontrol-related genes. An accurate, quantitative real-time PCR protocol with novel designed specific primers was developed to characterise strain-specific gene expression, that optimises strain-culturing and RNA-isolation methodologies. Six genes responsible for synthesising non-ribosomal peptide synthetase biocontrol metabolites were detected in all five strains. Three genes were involved in synthesising three Polyketide synthetase metabolites in all five strains, but the macrolactin synthase gene mln was only detected in WBN06 and YN1282-2. All five Bacillus strains have the genes dhb and bioA, essential for synthesising bacillibactin and biotin. However, the gene sboA, involved in subtilisin synthesis, is absent in all five strains. These genes' expression patterns were significantly different among these strains, suggesting different mechanisms involved in TR4 biocontrol. Results will help elucidate functional genes' biocontrol mechanisms.

New Disubstituted Quindoline Derivatives Inhibiting Burkitt's Lymphoma Cell Proliferation by Impeding c-MYC Transcription.

The c-MYC oncogene is overactivated during Burkitt's lymphoma pathogenesis. Targeting c-MYC to inhibit its transcriptional activity has emerged as an effective anticancer strategy. We synthesized four series of disubstituted quindoline derivatives by introducing the second cationic amino side chain and 5-N-methyl group based on a previous study of SYUIQ-5 (1) as c-MYC promoter G-quadruplex ligands. The in vitro evaluations showed that all new compounds exhibited higher stabilities and binding affinities, and most of them had better selectivity (over duplex DNA) for the c-MYC G-quadruplex compared to 1. Moreover, the new ligands prevented NM23-H2, a transcription factor, from effectively binding to the c-MYC G-quadruplex. Further studies showed that the selected ligand, 7a4, down-regulated c-MYC transcription by targeting promoter G-quadruplex and disrupting the NM23-H2/c-MYC interaction in RAJI cells. 7a4 could inhibit Burkitt's lymphoma cell proliferation through cell cycle arrest and apoptosis and suppress tumor growth in a human Burkitt's lymphoma xenograft.