ABSTRACT
Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Subject(s)
Humans , Brain Neoplasms/pathology , Neoplasm Recurrence, Local/metabolism , Glioma/pathology , Neural Stem Cells/pathology , Oligodendrocyte Precursor Cells/pathology , Tumor MicroenvironmentABSTRACT
OBJECTIVE：To study the protective effect of tadehaginoside（TA）on liver fibrosis model mice induced by carbon tetrachloride（CCl4），and to investigate its mechanism. METHODS ：Kunming mice were randomly divided into normal group ， model group ，colchicines group （positive control ，0.2 mg/kg），TA low-dose ，medium-dose and high-dose groups （3，6，12 mg/kg），with 10 mice in each group. Those groups were intraperitoneally injected with 10％ CCl4-olive oil solution （5 mL/kg）to induce liver fibrosis model twice a week ，for consecutive 8 weeks；except that ，the normal group was intraperitoneally injected with olive oil. From 3rd week ，the mice in each administration groups were given relevant medicine intragastrically ，normal group and model group were given constant volume 2％ sodium carboxymethylcellulose solution intragastrically ，once a day ，for consecutive 6 weeks. The contents of ALT ，AST，HA and IL- 6 in serum of mice were test ed by ELISA. The contents of Hyp ， SOD，MDA and GSH-Px in liver tissues were detected by spectrophotometry. mRNA expression of Col- Ⅰ，TIMP-1 and TIMP-2 in liver tissue was detected by RT-PCR. The protein expression of MMP- 2 and TGF-β1 in liver tissue was detected by Western blotting. RESULTS ： Compared with normal group，the contents of ALT，AST，HA，IL-6，MDA and Hyp，the mRNA expression of Col- Ⅰ，TIMP-1 and TIMP- 2，as well as the protein exp ression of MMP- 2 and TGF-β1 were increased significantly ，while the contents of SOD and GSH-Px were decreased significantly （P＜0.01）. Compared with model group，the contents of ALT ，AST，HA，IL-6，MDA and Hyp ，the mRNA expression of Col- Ⅰ，TIMP-1 and TIMP- 2，as well as the protein expression of MMP- 2 and TGF-β1were decreased significantly ，while the contents of SOD and GSH-Px were increased significantly（P＜0.05 or P＜0.01）. CONCLUSIONS ：TA has a significant protective effect on liver tissue and anti-fibrosis effects in liver fibrosis model mice ，the mechanism of which may be associated with inhibiting lipid peroxidation and collagen synthesis ， down-regulating the mRNA expression of Col- Ⅰ，TIMP-1 and TIMP- 2 as well as the protein expression of MMP- 2 and TGF-β1.
ABSTRACT
Aim To investigate the effect of plumbagin on invasion and apoptosis of human hepatocellular car-cinoma ( HepG2 ) . Methods HepG2 cells were cul-tured in vitro with different concentrations of plumba-gin, then cell proliferation was observed by MTT as-say; cell invasion was observed by transwell invasion assay; cell apoptosis was detected by flow cytometry, and the protein expression of Bax, Bcl-2 was detected by immunocytochemistry. Results MTT results showed that plumbagin could significantly inhibit cell proliferation compared with the control group, and in a dose-dependent manner ( P ( P < 0. 01 ) . Flow cytometry showed that apoptosis rate was significantly higher in 4 , 8 μmol · L-1 group of plumbagin compared with that of the control group ( P<0. 01 ) . Immunocytochemistry showed that, with the increasing concentration of plumbagin, Bax protein expression increased, Bcl-2 protein expression was de-creased, both in a dose-dependent manner ( P <0. 01 ) . Conclusion Plumbagin can inhibit HepG2 cell proliferation and accelerate apoptosis of HepG2 cells, but also has the ability to inhibit HepG2 cell in-vasion.
ABSTRACT
This study was aimed to observe the effects of Gui Curcuma extract on proliferation, collagen production, and matrix metalloproteinase (MMP) expression by hepatic stellate cells (HSC-LX2). HSC-LX2 were cultured in DMEM broth (10% FBS), then treated with Gui Curcuma extract (with the concentration of 0, 22.5, 45, 90 μmol·L-1) for 24 h. The proliferation of HSC-LX2 was measured by MTT assay; injury in HSC-LX2 was indicated with LDH re-lease; collagen I production was detected by ELISA; and MMP-l expression was determined by Western blot. The re-sults showed that Gui Curcuma extract (with the concentration of 22.5, 45, 90 μmol·L-1) dose-dependently inhibited proliferation of HSC-LX2 by 16.2%, 43.9%, 59.4% in MTT assay, respectively. The IC50 was 59.1 μmol·L-1. There was no significant impact on LDH release. The Gui Curcuma extract (with the concentration of 45, 90 μmol·L-1) can significantly reduce the expression of collagen I level (P< 0.01), whereas MMP-1 expression was significantly uplift-ed (P< 0.05) by Gui Curcuma extract (with the concentration of 45, 90 μmol·L-1) in Western blot. It was concluded that Gui Curcuma extract had the potential to prevent hepatic fibrosis, through inhibiting proliferation and collagen I production, and increasing MMP-1 protein expression.
ABSTRACT
Objective To explore the application effect of performance evaluation in bonus distribution in nurses working in otolaryngology department,and seek for the perfect solution of bonus distribution,motivate nurses' work enthusiasm,and therefore be helpful for the enhanced nursing quality andsafety.Methods Bonus coefficient was calculated according to technical title (make up 40％),position(make up 30％) and performance assessment(make up 30％).The occurrence of nursing defects,patients satisfaction degree,the scores of nursing performance,the scores of theoretical test and skill examination,and nurse satisfaction degree were compared between pre-and post-implementation of system.Results The above items showed significant differences before and after the practice of performance evaluation.Conclusions Bonus distribution according to performance evaluation can be effective in the improvement of nursing quality,patients' satisfaction degree and nurses' work enthusiasm,therefore be helpful for the enhanced nursing management level in otolaryngology department.