RESUMO
Breast cancer (BC) is among the most universal malignant tumors in women worldwide. Aging is a complex phenomenon, caused by a variety of factors, that plays a significant role in tumor development. Consequently, it is crucial to screen for prognostic aging-related long non-coding RNAs (lncRNAs) in BC. The BC samples from the breast-invasive carcinoma cohort were downloaded from The Cancer Genome Atlas (TCGA) database. The differential expression of aging-related lncRNAs (DEarlncRNAs) was screened by Pearson correlation analysis. Univariate Cox regression, LASSO-Cox analysis, and multivariate Cox analysis were performed to construct an aging-related lncRNA signature. The signature was validated in the GSE20685 dataset from the Gene Expression Omnibus (GEO) database. Subsequently, a nomogram was constructed to predict survival in BC patients. The accuracy of prediction performance was assessed through the time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, principal component analyses, decision curve analysis, calibration curve, and concordance index. Finally, differences in tumor mutational burden, tumor-infiltrating immune cells, and patients' response to chemotherapy and immunotherapy between the high- and low-risk score groups were explored. Analysis of the TCGA cohort revealed a six aging-related lncRNA signature consisting of MCF2L-AS1, USP30-AS1, OTUD6B-AS1, MAPT-AS1, PRR34-AS1, and DLGAP1-AS1. The time-dependent ROC curve proved the optimal predictability for prognosis in BC patients with areas under curves (AUCs) of 0.753, 0.772, and 0.722 in 1, 3, and 5 years, respectively. Patients in the low-risk group had better overall survival and significantly lower total tumor mutational burden. Meanwhile, the high-risk group had a lower proportion of tumor-killing immune cells. The low-risk group could benefit more from immunotherapy and some chemotherapeutics than the high-risk group. The aging-related lncRNA signature can provide new perspectives and methods for early BC diagnosis and therapeutic targets, especially tumor immunotherapy.
Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , RNA Longo não Codificante/genética , Prognóstico , Imunoterapia , Envelhecimento/genética , Tioléster Hidrolases , Proteínas MitocondriaisRESUMO
Four new guaiane-type sesquiterpenes, argyin H-K (1-4), and two known analogues (5 and 6) were isolated from the leaves of Artemisia argyi Lévl et Vant. The new compounds were characterized by the basic analysis of the spectroscopic data obtained (1H NMR, 13C NMR, HMBC, and NOESY experiments), and their absolute configurations were determined by empirical approaches, combined with the exciton chirality method and electronic circular dichroism calculations. To further understand the antitumor effects of A. argyi, the antiproliferative activities of these compounds against A549, MCF-7, and HepG2 cell lines were tested in vitro using CCK-8 assays. The results showed that these compounds had significant antiproliferative effects on MCF-7, with IC50 values of 15.13-18.63 µM, which were superior to that of oxaliplatin (i.e., IC50 22.20 µM).
RESUMO
Five new isoquinolines (1-5) were isolated from national herb Corydalis tomentella. Their structures were elucidated by extensive analysis of the 1D and 2D NMR spectra and from the HRESIMS. Absolute configurations of 1-3 were determined by comparing their experimental and computed ECD data. Since plants from Corydalis have been reported to protect against Alzheimer's disease, all compounds were evaluated for their neuroprotective effect against lipopolysaccharide-induced BV2 microglia cells. Compound 2 and 3 showed well anti-neuroinflammatory activity at low concentration (25 µM).