Investigation of the marine-derived fungus Pleosporales sp. CF09-1 cultured in modified PDB medium led to the isolation of six new azaphilone derivatives, pleosporalones B and C (1 and 2) and pleosporalones E−H (4−7), and one known analogue (3). The absolute configurations of C-2′ and C-3′ in 3 were assigned by a vibrational circular dichroism method. The C-11 relative configurations for the pair of C-11 epimers (4 and 5) were established by comparing the magnitude of the computed 13 C NMR chemical shifts (Δδ calcd ) with the experimental 13 C NMR values (Δδ exp ) for the epimers. Antiphytopathogenic and anti-Vibrio activities were evaluated for 1−7. Pleosporalone B (1) exhibited potent antifungal activities against the fungi Alternaria brassicicola and Fusarium oxysporum with the same MIC value of 1.6 μg/mL, which were stronger than the positive control ketoconazole among these compounds. Additionally, pleosporalone C (2) displayed significant activity against the fungus Botryosphaeria dothidea (MIC, 3.1 μg/mL). Compounds 6 and 7 displayed moderate anti-Vibrio activities against Vibrio anguillarum and Vibrio parahemolyticus, with MIC values of 13 and 6.3 μg/mL for 6 and 6.3 and 25 μg/mL for 7, respectively.
Retinoblastoma (RB) is a common malignant tumor in children. Lidocaine is a local anesthetic and anti-arrhythmic drug, and has been reported to possess anti-tumor properties. MicroRNAs (miRs) are a group of endogenous small noncoding RNAs that have important roles in various biological processes via actions on target genes. The aim of the present study was to investigate the effect of lidocaine on retinoblastoma
in vitro
and
in vivo
. CCK-8 assay and flow cytometry assay were used to measure cell viability and apoptosis. The relationship between miR-520a-3p and EGFR was predicted and confirmed by TargetScan and dual-luciferase reporter assay. For
in vivo
study, tumor xenograft was performed. In addition, gene and protein expression was detected using reverse transcription-quantitative polymerase chain reaction and western blotting respectively. In the present study, it was observed that lidocaine inhibited the proliferation and induced the apoptosis of RB cells. miR-520a-3p was reported to be downregulated in RB tissues and cell lines; treatment with lidocaine increased the expression of miR-520a-3p in RB cells. The human epidermal growth factor receptor (EGFR) was identified as a direct target of miR-520a-3p, and its expression was negatively associated with that of miR-520a-3p. Additionally, EGFR was upregulated in RB tissues and cell lines; treatment with lidocaine decreased the expression of EGFR in RB cells. Furthermore, compared with treatment with lidocaine alone, the combination of transfection with miR-520a-3p inhibitor and lidocaine treatment significantly decreased the expression of miR-520a-3p, increased EGFR expression, promoted RB cell proliferation and reduced the apoptosis of cells
in vitro
, and increased tumor volume and weight
in vivo
. The results indicated that lidocaine reduced the proliferation and induced the apoptosis of RB cells by decreasing EGFR expression via the upregulation of miR-520a-3p, suggesting that the miR-520a-3p/EGFR axis may be a novel therapeutic target in the treatment of RB.
Contemporary patients selected to have intentional IPAA for Crohn's colitis have disease characteristics very different from those selected to have ileorectal anastomosis. Long-term follow-up confirms intentional IPAA as an acceptable option in selected patients with Crohn's colitis.
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