Chaetocochin J exhibits anti-hepatocellular carcinoma effect independent of hypoxia.

The most studied epipolythiodioxopiperazine (ETP) alkaloids, such as chetomin, gliotoxin and chaetocin, were reported to exert their antitumor effects through targeting HIF-1α. Chaetocochin J (CJ) is another ETP alkaloid, of which the effect and mechanism on cancer are not fully elucidated. Considering the high incidence and mortality of hepatocellular carcinoma (HCC) in China, in the present study, using HCC cell lines and tumor-bearing mice as models, we explored the anti-HCC effect and mechanism of CJ. Particularly, we investigated whether HIF-1α is related to the function of CJ. The results showed that, both under normoxic and CoCl2 induced-hypoxic conditions, CJ in low concentrations (<1 µM) inhibits the proliferation, induces G2/M phase arrest, leading to the disorder of metabolism, migration, invasion, and caspase-dependent apoptosis in HepG2 and Hep3B cells. CJ also showed anti-tumor effect on a nude xenograft mice model without significant toxicity. Moreover, we demonstrated that the key to CJ's function is mainly associate with its inhibition of PI3K/Akt/mTOR/p70S6K/4EBP1 pathway independent of hypoxia, and it also could suppress the expression of HIF-1α as well as disrupt the binding of HIF-1α/p300 and subsequently inhibits the expression of its target genes under hypoxic condition. These results demonstrated that CJ possessed a hypoxia-independent anti-HCC effects in vitro and in vivo, which was mainly attributable to its inhibition on the upstream pathways of HIF-1α.

Near infrared light activatable PEI-wrapped bismuth selenide nanocomposites for photothermal/photodynamic therapy induced bacterial inactivation and dye degradation.

The inactivation of bacteria and the degradation of organic pollutants by engineered nanomaterials (NMs) are very effective approaches for producing safe and clean drinking water. The development of new NMs which can act as NIR light mediated antimicrobial agents as well as photocatalytic agents is highly desired. In this study, a novel Bi2Se3 nanoplates (NPs) NM was prepared by a high-temperature reaction (colloidal synthesis) followed by wrapping of the surface with polyethyleneimine (PEI) through electrostatic interactions. The developed Bi2Se3 NPs/PEI exhibited excellent NIR light activated antimicrobial properties for bacterial eradication and efficient photocatalytic properties for organic dye degradation. The results showed that upon 808 nm laser irradiation the engineered Bi2Se3 NPs/PEI eradicated ∼99% of S. aureus and ∼97% of E. coli bacteria within 10 minutes of irradiation through combined dual-modal photothermal therapy (PTT) and photodynamic therapy (PDT) via the generation of heat and reactive oxygen species, respectively. The contributions of PTT and PDT were found to be in a ratio of nearly 4 : 1 in the killing of both species of bacteria. In addition, Bi2Se3 NPs/PEI also acted as an excellent photocatalyst under illumination by a halogen lamp equipped with a 700-1100 nm band pass filter to achieve degradation efficiencies of ∼95% for methylene blue and ∼93% for Rhodamine B within 3 and 4 h, respectively. To the best of our knowledge, this is the first demonstration of these NIR light activated antimicrobial properties, photodynamic properties and photocatalytic properties mediated by Bi2Se3 NPs.

Citrinal B, natural 11 beta-hydroxysteroid dehydrogennase type 1 inhibitor identified from structure-based virtual screening.

Citrinal B, a tricyclic compound from endophytic fungus Colletotrichum capsici in our previous studies, exhibited significant inhibitory activity against 11ß-hydroxysteroid dehydrogenase type 1 (11 ß-HSD1) in vitro and showed strong binding affinity to 11ß-HSD1. Moreover, citrinal B treatments decreased the lipid droplet accumulation associate with the inhibition of 11ß-HSD1 expression in differentiate induced 3T3-L1 preadipocytes. Furthermore, the molecular docking demonstrated that citrinal B coordinated in the active site of 11ß-HSD1 is essential for the ability of diminishing the enzyme activity.