High paternal homocysteine causes ventricular septal defects in mouse offspring.

Maternal hyperhomocysteinemia is widely considered as an independent risk of congenital heart disease (CHD). However, whether high paternal homocysteine causes CHD remains unknown. Here, we showed that increased homocysteine levels of male mice caused decreased sperm count, sperm motility defect and ventricular septal defect of the offspring. Moreover, high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes. Folic acid supplement could decrease the occurrence of VSD in high homocysteine male mice. This study reveals that increased paternal homocysteine level increases VSD risk in the offspring, indicating that decreasing paternal homocysteine may be an intervening target of CHD.

Chamiside A, a Cytochalasan with a Tricyclic Core Skeleton from the Endophytic Fungus Chaetomium nigricolor F5.

Chamiside A (1), a novel cytochalasan with a new 6/6/5-fused tricyclic core skeleton, was isolated from an endophytic fungus, Chaetomium nigricolor F5, harbored in the medicinal plant Mahonia fortunei. Its structure was unambiguously determined by extensive spectroscopic analyses, measurement of single-crystal X-ray diffraction, and electronic circular dichroism calculation. A biosynthetic pathway for the unique ring system in 1 was proposed. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus.

Diterpenoids from the Chinese liverwort Frullania hamatiloba and their Nrf2 inducing activities.

Six previously undescribed labdane diterpenoids, frullanians A-F, along with five known diterpenoids, were isolated from the Chinese liverwort Frullania hamatiloba Stephani. Their structures were determined using NMR data, electronic circular dichroism (ECD) calculations as well as the single crystal X-ray diffraction measurement. NAD(P)H: QR (quinone reductase) assay demonstrated that frullanian D and four known compounds displayed antioxidant effect mediated via Nrf2 (Nuclear factor-erythroid 2-related factor 2) induction. Further investigation of the most bioactive frullanian D in MOVAS cells revealed that it ameliorated H2O2-induced oxidative insults without toxicity by increasing cell viability, attenuating morphological changes, and reducing intracellular ROS production. In addition, frullanian D promoted the nuclear translocation of Nrf2 and upregulated the expressions of antioxidant proteins NQO1 (NAD(P)H quinone oxidoreductase 1) and γ-GCS (γ-glutamyl cysteine synthetase). Docking analysis using MOE software further supported the activation of the Nrf2 pathway by frullanian D.

Heptaketides from the endophytic fungus Pleosporales sp. F46 and their antifungal and cytotoxic activities.

Six new heptaketides, pleosporalins A-F (1-5, and 7), and a new heptaketide derivative, pleosporalin G (9), together with four biosynthetically related known compounds (6, 8, 10, and 11), were isolated from an endophytic fungus, Pleosporales sp. F46, found in the medicinal plant Mahonia fortunei. The structures and stereochemistry of these compounds were established by extensive spectroscopic analyses including LC-HRMS, NMR spectroscopy, optical rotations, ECD calculations, and single-crystal X-ray diffraction. The antifungal activities of isolated compounds 1-11 were investigated against Candida albicans, and their cytotoxic activities were evaluated against A549, SMMC-721, and MDA-MB-231 cancer cell lines. Compound 1 was active against C. albicans with an MIC80 of 128 µg mL-1, and compound 7 showed moderate cytotoxicity against MDA-MB-231 with an IC50 of 22.4 ± 1.1 µM. By comparing compounds 1 and 7 with structurally related metabolites, it was revealed that alterations to their C-1 or C-2 substitutions could significantly influence their antifungal or cytotoxic efficacies.

ent-Eudesmane-Type Sesquiterpenoids from the Chinese Liverwort Chiloscyphus polyanthus var. rivularis.

Seven new ent-eudesmane-type sesquiterpenoids (1-7) and six known analogues (8-13) were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were determined from analysis of MS and NMR spectroscopic data and single-crystal X-ray diffraction. A cytotoxic evaluation showed that compound 1 exhibited weak inhibitory activity against the A549 cancer cell line with an IC50 value of 27.7 µM.