陈鹤
青岛市阜外心血管病医院
The aim of the present study was to investigate the small molecule anticancer agents in the medicinal fungus Inonotus obliquus and further characterize their possible molecular mechanisms. Chemical fractionation of the ethanol extract of this fungus yielded a panel of lanostane triterpenoids (1-13) and their structures were characterized on the basis of spectroscopic methods. Subsequent preliminary biological screening on these triterpenoids revealed significant cytotoxicity against various tumor cell lines, and inonotsutriol E (ITE, 1) showed the best activity. Of note, ITE displayed stronger inhibitory effect on breast cancer (BC) than other tumor cell lines. Functional assays revealed that ITE significantly inhibited the growth and migration of BC cells and exerted promising antitumor activity in patient-derived organoids (PDO). Further mechanistic study demonstrated that the anti-BC activity of ITE was achieved via inhibiting JAK2/STAT3 signal axis. Taken together, the current work has demonstrated the therapeutic material basis of I. obliquus and provided further evidence for the traditional application of this medicinal species in cancer prevention and treatment.
Bioorganic chemistry 2023
Transcriptomics studies have yielded great insights into disease processes by detecting differentially expressed genes (DEGs). In this study, due to the high heritability of Parkinson's disease (PD), we performed bioinformatics analyses on nine transcriptomic datasets regarding substantia nigra from Gene Expression Omnibus database, including seven microarray datasets and two next-generation sequencing datasets. As a result, between age-matched PD patients and normal control, we identified 630 DEGs, of which 22 hub DEGs involved in PD or ferroptosis were found to be associated with each other at the transcriptional level and protein-protein interaction network, suggesting their high correlations among these hub genes. Moreover, 16 DEGs were singled out due to their comparable AUC (>0.6) in random forest classifiers, including seven PD-related genes (MAP4K4, LRP10, UCHL1, PAM, RIT2, SNCA, GCH1) and nine ferroptosis-related genes (GCH1, DDIT4, RGS4, MAPK9, CAV1, RELA, DUSP1, ATP6V1G2, ATF4 and ISCU). Furthermore, to probe the potential of those hub genes in predicting the PD progression and survival, we constructed a Cox model featured by an eight-gene signature, including four PD-related genes (SNCA, UCHL1, LRP10, and GCH1) and four ferroptosis-related genes (DDIT4, RGS4, RELA, and CAV1), and validated it successful in an independent dataset, indicating that it would be an effective tool for clinical research to predict PD progression. In conclusion, ferroptosis-related DEGs identified in this study were closely correlated with the known PD-related genes, revealing the involvement of ferroptosis in the development of PD. This study presented the potential of several ferroptosis-related genes as novel clinical biomarkers for PD.
Computational and structural biotechnology journal 2022
