Association between ACE1 and missed abortion: ACE1 promotes H2O2-induced trophoblast cell injury in vitro†.

The aim of this study was to evaluate the role of angiotensin-converting enzyme 1 (ACE1) in H2O2-induced trophoblast cell injury and the potential molecular mechanisms. Oxidative stress was modeled by exposing HTR-8/SVneo cells to 200 µM H2O2. Western blot and real-time quantitative PCR methods were used to detect protein and mRNA expression level of ACE1 in chorionic villus tissue and trophoblast HTR-8/SVneo cell. Inhibition of ACE1 expression was achieved by transfection with small interfering RNA. Then flow cytometry, Cell Counting Kit-8, and Transwell assay was used to assess apoptosis, viability, and migration ability of the cells. Reactive oxygen species (ROS) were detected by fluorescent probes, and malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) activities were determined by corresponding detection kits. Angiotensin-converting enzyme 1 expression was upregulated in chorionic villus tissue of patients with missed abortion (MA) compared with individuals with normal early pregnancy abortion. H2O2 induced elevated ACE1 expression in HTR-8/SVneo cells, promoted apoptosis, and inhibited cell viability and migration. Knockdown of ACE1 expression inhibited H2O2-induced effects to enhance cell viability and migration and suppress apoptosis. Additionally, H2O2 stimulation caused increased levels of ROS and MDA and decreased SOD and GSH activity in the cells, whereas knockdown of ACE1 expression led to opposite changes of these oxidative stress indicators. Moreover, knockdown of ACE1 attenuated the inhibitory effect of H2O2 on the Nrf2/HO-1 pathway. Angiotensin-converting enzyme 1 was associated with MA, and it promoted H2O2-induced injury of trophoblast cells through inhibiting the Nrf2 pathway. Therefore, ACE1 may serve as a potential therapeutic target for MA.

(+)- and (-)-trichodermatrione A: a pair of enantiomers with a cyclobutane-containing skeleton from the endophytic fungus Trichoderma sp. EFT2.

(±)-trichodermatrione A, a pair of cyclobutane-containing enantiomers with an undescribed tricyclic 6/4/6 skeleton, was isolated from Trichoderma sp. EFT2, an endophytic fungus from Euonymus fortunei (Turcz.) Hand.-Mazz (Celastraceae). The racemates were separated by chiral HPLC with the structures elucidated by a combination of MS, NMR, ECD calculation and X-ray crystallography analyses. (±)- trichodermatrione A and enantiomers were found to be antibacterial against phytopathogenic bacteria Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc).

Novel metabolites from the Cercis chinensis derived endophytic fungus Alternaria alternata ZHJG5 and their antibacterial activities.

BACKGROUND: Phytopathogenic bacteria, such as Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (Rs), seriously threaten crop production and are the cause of enormous yield losses. Endophytic fungi are abundant sources of bioactive metabolites that may be potential candidates in the development of new agrochemicals. This work emphasizes the discovery of bioactive polyketides from endophytic Alternaria alternata ZHJG5 and reports their structural elucidation and antibacterial activities in detail. RESULTS: Five novel polyketide derivatives, isotalaroflavone (2), (+/-)-5'-dehydroxytalaroflavone (3a/3b), (+)-talaroflavone (4b), and bialternacin G (7), along with five known compounds (1, 4a, 5, 6, and 8), were obtained from the Cercis chinensis-derived fungus A. alternata ZHJG5. The compounds' structures were characterized using spectroscopic methods and X-ray diffraction. Chiral high-performance liquid chromatography was used to separate the racemates 3 and 4, whose absolute configurations were unambiguously confirmed by comparing their experimental and calculated electron circular dichroism data. All isolated compounds were tested for antibacterial activity against the phytopathogenic bacteria Xoo, Xanthomonas oryzae pv. oryzicola (Xoc) and Rs. Compounds 1, 2 and 8 showed pronounced antibacterial activity against all tested bacteria, with minimal inhibitory concentrations ranging from 0.5 to 64 µg/ml. In addition, compound 1 showed a potent protective effect against rice bacterial leaf blight caused by Xoo with a protective efficacy of 75.1% at a concentration of 200 µg/ml. CONCLUSION: These findings highlight the practical potential of antibacterial compounds as candidates for the discovery of novel bactericides. © 2021 Society of Chemical Industry.

Enantiomeric Dibenzo-α-Pyrone Derivatives from Alternaria alternata ZHJG5 and Their Potential as Agrochemicals.

Three pairs of enantiomeric dibenzo-α-pyrone derivatives (1-3) including two pairs of new racemates (±)-alternaone A (1) and (±)-alternaone B (2) and one new enantiomer (-)-alternatiol (3), together with five known compounds (4-8) were isolated from the fungus Alternaria alternata ZHJG5. Their structures were confirmed by spectroscopic data and single-crystal X-ray diffraction analysis. All enantiomers were separated via chiral high-performance liquid chromatography, with their configurations determined by electronic circular dichroism calculation. Biogenetically, a key epoxy-rearrangement step was proposed for the formation of skeletons in 1-3; (+) 1, (-)-1, and 5 presented moderate antibacterial inhibition on phytopathogenic bacteria Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola. In the antifungal test, compounds 7 and 8 showed a moderate protective effect against Botrytis cinerea in vivo.

Discovery of Natural FabH Inhibitors Using an Immobilized Enzyme Column and Their Antibacterial Activity against Xanthomonas oryzae pv. oryzae.

ß-Ketoacyl-acyl carrier protein synthase III (KAS III, FabH) is essential for bacterial fatty acid biosynthesis. Recent studies indicate that FabH can be a potential target for bactericide development. In the present study, an immobilized FabH column was developed and used to screen FabH inhibitors from complex natural product extracts. Combined with HPLC, four secondary metabolites, alternariol (1), altenuisol (2), alterlactone (3), and dehydroaltenusin (4), were site-directed, isolated, and identified from the crude extract of Alternaria alternata ZHJG5. These compounds showed inhibitory activities on FabH of Xanthomonas oryzae pv. oryzae (Xoo) with IC50 values from 29.5 to 74.1 µM and also displayed a varying degree of antibacterial activities against Xoo with minimal inhibitory concentration values from 4 to 64 µg/mL. Molecular modeling was then used to picture how the compounds interact with XooFabH. Two inhibitors, compounds 1 and 3, exhibited significant bactericidal activity against rice bacterial leaf blight with a protective efficiency of 66.2 and 82.5% at the concentration of 200 µg/mL, respectively, suggesting that they could be lead candidates to develop novel bactericides.