Euphoesulatin A prevents osteoclast differentiation and bone loss via inhibiting RANKL-induced ROS production and NF-κB and MAPK signal pathways.

Euphoesulatin A (Eup A), a new jatrophane diterpenoid isolated from the Euphorbia esula L. (Euphorbiaceae), was reported to inhibit RANKL-induced osteoclastogenesis. However, the underlying mechanism and the effect in osteoporosis mouse model are still unclear.

Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase.

The polyketide natural product reveromycin A (RM-A) exhibits antifungal, anticancer, anti-bone metastasis, anti-periodontitis and anti-osteoporosis activities by selectively inhibiting eukaryotic cytoplasmic isoleucyl-tRNA synthetase (IleRS). Herein, a co-crystal structure suggests that the RM-A molecule occupies the substrate tRNA binding site of Saccharomyces cerevisiae IleRS (ScIleRS), by partially mimicking the binding of tRNA. RM-A binding is facilitated by the copurified intermediate product isoleucyl-adenylate (Ile-AMP).

Molecular Characterization of -Carrying in Henan Province of China.

Carbapenem-resistant (CRE) pose a serious threat to clinical management and public health. We investigated the molecular characteristics of 12 IMP-4 metallo-β-lactamase-producing strains, namely, 5 , 3 , 2 , and 2 . These strains were collected from a tertiary teaching hospital in Zhengzhou from 2013 to 2015.

Synthesis and evaluation of andrographolide derivatives as potent anti-osteoporosis agents in vitro and in vivo.

In this work, we found that 14-deoxy-11,12-didehydroandrographolide (2), a derivative of andrographolide (AP, 1), had greatly reduced cytotoxicity compared with AP and exhibited moderate anti-osteoclastogenesis activity. Thirty compounds were synthesized by introducing anti-osteoporosis chemotypes at C-19 of 2. Six of them exhibited stronger inhibition of osteoclastogenesis than AP.

Discovery of novel liver X receptor inverse agonists as lipogenesis inhibitors.

Based on the co-crystal structures of LXRβ and its agonists (spiro [pyrrolidine-3,3'-oxindole] derivatives) discovered by us previously, we designed and synthesized a compound library to explore the agonistic activities. The library was screened with luciferase reporter assays, interestingly, it resulted in the discovery of 10 LXR inverse agonists besides 5 LXR agonists. To clarify the mechanism of the actions, we conducted molecular dynamics (MD) simulations on the LXR and inverse agonists complexes, and revealed that H3, H11 and H12 configurations are the key to turn on agonism or inverse agonism status for LXR.