[Research progress on the role of HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis].

Hypoxia-inducible factors (HIFs) are one of the primary transcription factors regulating oxygen balance, and their stability is determined by the hydroxylation state of the prolyl hydroxylase domain (PHD) that is sensitive to oxygen. In recent years, studies have shown that HIFs-prolyl hydroxylases (PHDs) oxygen-sensing pathway is involved in the process of cellular ferroptosis. Ferroptosis, a new type of cell death, different from necrosis, apoptosis, necrotizing apoptosis, and pyroptosis, is essentially a programmed death caused by the accumulation of iron-dependent lipid peroxides in cells. This paper focuses on the role and mechanism of the HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis involved in nerve diseases, tumors, lung injury, and chemical nerve damage from three aspects of iron metabolism, lipid metabolism, and glutathione (GSH) synthesis/metabolism. This review will provide a theoretical basis and new ideas for the development of novel drugs targeting the HIFs-PHDs oxygen-sensing pathway and capable of regulating ferroptosis for the treatment of diseases related to ferroptosis such as nervous system diseases and tumors.

A new cytotoxic trichothecene macrolide from the endophyte Myrothecium roridum.

A new cytotoxic roridin-type trichothecene macrolide named roritoxin E(1) was characterized from the solid culture of Myrothecium roridum IFB-E091 (residing originally inside Artemisia annua root), together with the known compounds lumichrome (2), (22 E,24 S)-cerevisterol (3), and (22 E,24 R)-6 beta-methoxy-ergosta-7,22-diene-3 beta,5 alpha-diol (4). The structure of the new macrolide (1) was elucidated by a combination of spectroscopic (UV, IR, MS, and 1D and 2D NMR) analyses. Compound 1 was demonstrated to be inhibitory in vitro against the gastric carcinoma SGC-7901 and hepatocarcinoma SMMC-7721 cell lines, with IC (50) values of 0.26 and 10.54 microg/mL, respectively. 5-Fluorouracil co-assayed as a positive control had an IC (50) value of 6.66 microg/mL against SGC-7901 cells, and it demonstrated only a 9.98 % growth inhibition against SMMC-7721 cells at 10 microg/mL.

Bis(1,2,3,4-tetra-hydro-quinolin-6-yl)methane.

The asymmetric unit of the title compound, C(19)H(22)N(2), contains one half-mol-ecule. The 1,2,3,4-tetra-hydro-quinoline units are linked by a methyl-ene bridge, which lies on a twofold rotation axis. The non-aromatic ring adopts a flattened-boat conformation. The dihedral angle between the two symmetry-related benzene rings is 64.03 (7)°.

[Molecular simulations of the loading of methadone and buprenorphine into carbon nanotubes].

AIM: To simulate the inhalation of the C21H27NO and C29H41NO4 molecules, the effective components of methadone and buprenorphine, into carbon nanotubes, and discuss the feasibility of the loading of methadone and buprenorphine into carbon nanotubes. METHODS: The MM + force-field based molecular dynamics (MD) method uas used. RESULTS: The ends-opened carbon nanotubes with diameter larger than 1 or 1.25 nm can initiatively inhale the C21H27 NO or C29H41NO4 molecule, and both two molecules have higher potential energy at the open ends of the carbon tubes than that at the middle of the tubes; the present single-walled nanotubes are very suitable for the loading of methadone and buprenorphine. CONCLUSION: It is possible to make sustained-release detoxification agents with methadone- or buprenorphine-loaded carbon nanotubes.