[ABSTRACT]AIM:ToinvestigatetheeffectoforidoninontheinvasionandmigrationofhumanlungcancerNCI-H460 cells.METHODS:NCI-H460 cells were divided into high-dose (HD), middle-dose (MD) and low-dose (LD) oridonin groups (cultured with 40, 20 and 10μmol/L of oridonin, respectively, as experimental groups), and normal (N) group ( treated without oridonin as control ) .The cell growth was observed .The cell proliferation was detected by MTT as-say.Boyden chamber was used to determine the cell invasive capacity .The cell migration was also measured .The levels of MMP-2 and MMP-9 were assayed by Western blotting .RESULTS:The cell counts in the experimental groups were lower than that in N group .The cell proliferation was inhibited as the inhibitory rates were 48.94%, 36.17%and 19.15% for HD group, MD group and LD group, respectively.The numbers of the invasive cells were 26.67 ±5.16 for HD group, 36.17 ±5.08 for MD group, and 44.33 ±5.50 for LD group.The migration rates in the experimental groups were lower than that in N group .The expression of MMP-2 and MMP-9 decreased dependent on the oridonin dose as follows: HD group

Animals ; Antimicrobial Cationic Peptides ; chemistry ; pharmacology ; Fluorescence Resonance Energy Transfer ; Humans ; Peptide Chain Elongation, Translational ; drug effects ; Single Molecule Imaging

Ambystoma mexicanum/immunology* ; Amputation ; Animals ; Biomarkers/metabolism* ; Blastomeres/immunology* ; Cell Lineage/immunology* ; Connective Tissue Cells/immunology* ; Epithelial Cells/immunology* ; Forelimb ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Immunity ; Peroxiredoxins/immunology* ; Regeneration/immunology* ; Regenerative Medicine/methods* ; Single-Cell Analysis/methods*

Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3K27M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.
Animals ; Brain Stem Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cellular Senescence ; Female ; Glioma ; genetics ; metabolism ; pathology ; Histones ; genetics ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Transplantation ; Neoplastic Stem Cells ; drug effects ; metabolism ; pathology ; Neural Stem Cells ; drug effects ; metabolism ; pathology ; Pons ; embryology ; metabolism ; pathology ; Primary Cell Culture

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis