Celastrol promotes apoptosis of breast cancer MDA-MB-231 cells by targeting HSDL2

Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.

通过鉴定关键靶标蛋白探究青蒿素抗疟机制

The widespread use of artemisinin(ART)and its derivatives has significantly reduced the global burden of malaria;however,malaria still poses a serious threat to global health.Although significant progress has been achieved in elucidating the antimalarial mechanisms of ART,the most crucial target proteins and pathways of ART remain unknown.Knowledge on the exact antimalarial mechanisms of ART is urgently needed,as signs of emerging ART resistance have been observed in some regions of the world.Here,we used a combined strategy involving mass spectrometry-coupled cellular thermal shift assay(MS-CETSA)and transcriptomics profiling to identify a group of putative antimalarial targets of ART.We then conducted a series of validation experiments on five prospective protein targets,demonstrating that ART may function against malaria parasites by interfering with redox homeostasis,lipid metabolism,and protein synthesis processes.Taken together,this study provides fresh perspectives on the antimalarial mechanisms of ART and identifies several crucial proteins involved in parasite survival that can be targeted to combat malaria.

Reaction in situ found in the synthesis of a series of lanthanide sulfate complexes and investigation on their structure, spectra and catalytic activity

A series of lanthanide sulfates coordination complexes, Ln2(SO4)3(H2O)8 (Ln = Pr (1), Nd (2), Tb (3), Sm (4), Dy (5), Gd (7), Ho (8)), and EuK(SO4)2 (6), were constructed by the reaction in situ of lanthanide ions (Ln3+) with flexible dodecanedioic acid and rigid aromatic 5-sulfosalicylic acid under hydrothermal conditions. All of them were characterized by elemental analysis, IR spectroscopy, and single-crystal X-ray diffraction. The crystal structures and coordination modes of metal centers and sulfate ions, as well as the novel reaction mechanism and different conditions of lanthanide ions and 5-sulfosalicylic acid to form the series of lanthanide sulfate complexes, were discussed in detail. Solid-state properties for these crystalline materials, such as thermal stability and powder X-ray diffraction have been investigated. Additionally, the photoluminescent characterizations of the complexes 3, 4, 5 and 6, and the catalytic properties of all the complexes about cyclohexane being oxidized into cyclohexanone/cyclohexanol were investigated and compared.

Two-faced OsNAS3 influences disease resistance via nicotianamine and ethylene

Plants have evolved a two-tiered immune system:pathogen-associated molecular pattern(PAMP)-triggered immunity(PTI)and effector-triggered immunity(ETI)(Yuan et al.,2021).Rice blast is the most devastating fungal disease affecting rice(Oryza sativa).