Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.     

Bacillus amyloliquefaciens Ameliorates H2O2-Induced Oxidative Damage by Regulating Transporters,Tight Junctions,and Apoptosis Gene Expression in Cell Line IPEC-1

Probiotics have always been considered as a supplementary therapy for many diseases especially gut disorders. The absorption and barrier function of the gut play a vital role in the maintenance of body homeostasis. This study was to investigate the protective effects of Bacillus amyloliquefaciens SC06 (Ba) on H₂O₂-induced oxidative stress on intestinal porcine epithelial cells (IPEC-1) based on the level of gene expression. We demonstrated that Ba was a safe probiotic strain in the first place. Results showed that treatment with H₂O₂ significantly increased the mRNA expression of absorptive transporters glucose transporter 2 (GLUT2), Ala/Ser/Cys/Thr transporter 1 (ASCT1), and ASCT2 compared with the control group. Meanwhile, oxidative stress induced a significant improvement in the mRNA expression of occludin (OCLN) and caspase-3, and remarkably inhibited the expression of L-type amino acid transporter 1 (LAT1) or B cell lymphoma-2 (Bcl-2), respectively. Pretreatment with Ba dramatically reversed the disturbance induced by oxidative stress on the mRNA expression of ASCT1, ASCT2, and OCLN, which also significantly prevented H₂O₂-inhibited LAT1 and Bcl-2 mRNA expression. However, Ba failed to exert any significant protective effect on GLUT2 and caspase-3 mRNA expression. We concluded that pretreatment with Ba could alleviate the damage caused by oxidative stress to a certain extent and conferred a protective effect to the intestine.

     

The Chimonanthus salicifolius genome provides insight into magnoliid evolution and flavonoid biosynthesis

Chimonanthus salicifolius, a member of the Calycanthaceae of magnoliids, is one of the most famous medicinal plants in Eastern China. Here, we report a chromosome‐level genome assembly of C. salicifolius, comprising 820.1 Mb of genomic sequence with a contig N50 of 2.3 Mb and containing 36 651 annotated protein‐coding genes. Phylogenetic analyses revealed that magnoliids were sister to the eudicots. Two rounds of ancient whole‐genome duplication were inferred in the C. salicifolious genome. One is shared by Calycanthaceae after its divergence with Lauraceae, and the other is in the ancestry of Magnoliales and Laurales. Notably, long genes with > 20 kb in length were much more prevalent in the magnoliid genomes compared with other angiosperms, which could be caused by the length expansion of introns inserted by transposon elements. Homologous genes within the flavonoid pathway for C. salicifolius were identified, and correlation of the gene expression and the contents of flavonoid metabolites revealed potential critical genes involved in flavonoids biosynthesis. This study not only provides an additional whole‐genome sequence from the magnoliids, but also opens the door to functional genomic research and molecular breeding of C. salicifolius.     

HDAC6 inhibitor WT161 performs anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU

Background: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of the present study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms.Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo.Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of protein kinase-B (AKT). More importantly, WT161 showed synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo.Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.     

Studies on the effects of bone marrow stem cells on mitochondrial function and the alleviation of ARDS

Molecular and Cellular Biochemistry - Mesenchymal stem cells (MSCs) can alleviate acute respiratory distress syndrome (ARDS), but the mechanisms involved are unclear, especially about their...     

CircKIF2A contributes to cell proliferation,migration, invasion and glycolysis in human neuroblastoma by regulating miR-129-5p/PLK4 axis

Molecular and Cellular Biochemistry - Multiple circular RNAs (circRNAs) have been identified to act as essential mediators in diverse human cancers. However, the roles of circRNAs in neuroblastoma...     

Genetics and Resistance Mechanism of the Cucumber (Cucumis sativus L.) Against Powdery Mildew

Journal of Plant Growth Regulation - Powdery mildew (PM) is one of the most severe foliar diseases in cucumbers (Cucumis sativus L.), but the inheritance of PM resistance remains unclear. The...