Two nematicidal furocoumarins from <i>Ficus carica</i> L. leaves and their physiological effects on pine wood nematode (<i>Bursaphelenchus xylophilus</i>)

<p>The ethanol extract of the <i>Ficus carica</i> L. leaves was tested to show strong nematicidal activity against pine wood nematode (PWN), <i>Bursaphelenchus xylophilus</i>, causing 90.93% corrected mortality within 72 h at 1.0 mg/mL. From the ethyl acetate soluble fraction of the <i>F. carica</i> L. leaves extract, the main nematicidal constituents were obtained by bioassay-guided isolation and identified as linear furocoumarins bergapten <b>(1)</b> and psoralen <b>(2)</b> by mass and NMR spectral data analysis. Bergapten and psoralen had significant nematicidal activity against PWN with the LC₅₀ values of 97.08 aKSnd 115.03 μg/mL within 72 h, respectively. The two furocoumarins could inhibit the activities of amylase, cellulase and acetylcholinesterase (AchE) from PWN. The morphologies of PWNs changed much after they were treated by bergapten and psoralen. The physiological effects of bergapten and psoralen on PWN might provide helpful clues to elucidate their nematicidal mechanisms.</p

Cytotoxic Dibohemamines D–F from a <i>Streptomyces</i> Species

Three dimeric analogues of bohemamines, dibohemamines D–F (<b>1</b>–<b>3</b>), together with dibohemamine A (<b>4</b>), were isolated from <i>Streptomyces</i> sp. CPCC 200497. Their structures were solved using a combination of mass spectrometry, 1D and 2D NMR spectroscopy, and CD. Dibohemamines D and E were new dimeric analogues of bohemamines, and dibohemamine F was a known compound obtained previously by semisynthesis. Dibohemamine F displayed potent cytotoxicity against cancer cell lines A549 and HepG2 with IC₅₀ values of 1.1 and 0.3 μM, respectively. Dibohemamines D and E showed moderate cytotoxicity against cancer cell lines A549 and HepG2

Table_1_Methylprednisolone is related to lower incidence of postoperative bleeding after flow diverter treatment for unruptured intracranial aneurysm.DOCX

Background and objectivesRegarding the anti-inflammatory effect, methylprednisolone is a candidate to prevent patients with unruptured intracranial aneurysms (UIAs) from postoperative bleeding (PB) after flow diverter (FD) treatment. This study aimed to investigate whether methylprednisolone is related to a lower incidence of PB after FD treatment for UIAs.MethodsThis study retrospectively reviewed UIA patients receiving FD treatment between October 2015 and July 2021. All patients were observed until 72  h after FD treatment. The patients receiving methylprednisolone (80  mg, bid, for at least 24 h) were considered as standard methylprednisolone treatment (SMT) users, otherwise as non-SMT users. The primary endpoint indicated the occurrence of PB, including subarachnoid hemorrhage, intracerebral hemorrhage, and ventricular bleeding, within 72 h after FD treatment. This study compared the incidence of PB between SMT users and non-SMT users and investigated the protective effect of SMT on PB after FD treatment using the Cox regression model. Finally, after controlling the potential factors related to PB, we performed subgroup analysis to further confirm the protective effect of SMT on PB.ResultsThis study finally included 262 UIA patients receiving FD treatment. PB occurred in 11 patients (4.2%), and 116 patients (44.3%) received SMT postoperatively. The median time from the end of surgery to PB was 12.3 h (range: 0.5–48.0 h). SMT users had a lower incidence of PB comparing with non-SMT users (1/116, 0.9% vs. 10/146, 6.8%, respectively; p = 0.017). The multivariate Cox analysis demonstrated that SMT users (HR, 0.12 [95%CI, 0.02–0.94], p = 0.044) had a lower risk of PB postoperatively. After controlling the potential factors related to PB (i.e., gender, irregular shape, surgical methods [FD and FD + coil] and UIA sizes), the patients receiving SMT still had a lower cumulative incidence of PB, comparing with patients receiving non-SMT (all p ConclusionSMT was correlated with the lower incidence of PB for patients receiving FD treatment and may be a potential method to prevent PB after the FD treatment.</p

Saccharothrixones A–D, Tetracenomycin-Type Polyketides from the Marine-Derived Actinomycete <i>Saccharothrix</i> sp. 10-10

Saccharothrixones A–C (<b>1</b>–<b>3</b>), three new aromatic polyketide <i>seco</i>-tetracenomycins, and saccharothrixone D (<b>4</b>), a new tetracenomycin analogue possessing opposite configurations at all of the stereogenic centers, were isolated from the marine-derived actinomycete <i>Saccharothrix</i> sp. 10-10. Compounds <b>1</b>–<b>3</b> represent the first examples of <i>seco</i>-tetracenomycins where the quinone ring B is cleaved and re-formed into a furanone ring. Their structures were elucidated by spectroscopic analyses and ECD calculations. The absolute configuration of <b>4</b> was confirmed by single-crystal X-ray diffraction analysis. Saccharothrixone D (<b>4</b>) showed <i>in</i> <i>vitro</i> cytotoxic activity against the HepG2 cancer cell line with an IC₅₀ value of 7.5 μM

Saccharothrixones A–D, Tetracenomycin-Type Polyketides from the Marine-Derived Actinomycete <i>Saccharothrix</i> sp. 10-10

Saccharothrixones A–C (<b>1</b>–<b>3</b>), three new aromatic polyketide <i>seco</i>-tetracenomycins, and saccharothrixone D (<b>4</b>), a new tetracenomycin analogue possessing opposite configurations at all of the stereogenic centers, were isolated from the marine-derived actinomycete <i>Saccharothrix</i> sp. 10-10. Compounds <b>1</b>–<b>3</b> represent the first examples of <i>seco</i>-tetracenomycins where the quinone ring B is cleaved and re-formed into a furanone ring. Their structures were elucidated by spectroscopic analyses and ECD calculations. The absolute configuration of <b>4</b> was confirmed by single-crystal X-ray diffraction analysis. Saccharothrixone D (<b>4</b>) showed <i>in</i> <i>vitro</i> cytotoxic activity against the HepG2 cancer cell line with an IC₅₀ value of 7.5 μM

Structure-Based Design of Novel Chemical Modification of the 3′-Overhang for Optimization of Short Interfering RNA Performance

Short interfering RNAs (siRNAs) are broadly used to manipulate gene expression in mammalian cells. Although chemical modification is useful for increasing the potency of siRNAs <i>in vivo</i>, rational optimization of siRNA performance through chemical modification is still a challenge. In this work, we designed and synthesized a set of siRNAs containing modified two-nucleotide 3′-overhangs with the aim of strengthening the interaction between the 3′-end of the siRNA strand and the PAZ domain of Ago2. Their efficiency of binding to the PAZ domain was calculated using a computer modeling program, followed by measurement of RNA–Ago2 interaction in a surface plasmon resonance biochemical assay. The results suggest that increasing the level of binding of the 3′-end of the guiding strand with the PAZ domain, and/or reducing the level of binding of the sense strand through modifying the two-nucleotide 3′-overhangs, affects preferential strand selection and improves siRNA activity, while we cannot exclude the possibility that the modifications at the 3′-end of the sense strand may also affect the recognition of the 5′-end of the guiding strand by the MID domain. Taken together, our work presents a strategy for optimizing siRNA performance through asymmetric chemical modification of 3′-overhangs and also helps to develop the computer modeling method for rational siRNA design