Metabolic and proteostatic differences in quiescent and active neural stem cells

Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

Effects of Electroacupuncture at the Conception Vessel on Proliferation and Differentiation of Nerve Stem Cells in the Inferior Zone of the Lateral Ventricle in Cerebral Ischemia Rats

Objective： To observe the effects of electroacupuncture （EA） at the Conception Vessel on proliferation and differentiation of the nerve stem cells in the inferior zone of the lateral ventricle in cerebral ischemia rats. Methods： The model rats were prepared by occlusion of the middle cerebral artery for 2 hours and then by reperfusion. They were randomly divided into two groups： a control group and an EA group. Changes in differentiation and proliferation of the nerve stem cells were observed 7, 14 and 28 days after successful modeling. Results： As compared with the 7-day control group （C-7d group）, there was no significant difference （P〉0.05） in the numbers of 5-bromodeoxyuridine （Brdu） positive cells, Brdu/GFAP, Brdu/Nestin and Brdu/Nse double-labeled cells in the inferior zone of the lateral ventricle in the EA group 7 days after modeling. However, in the 14-day EA group （R-14d group） and the 28-day EA group （R-28d group）, the numbers of Brdu positive cells and Brdu/GFAE Brdu/Nestin, Brdu/Nse double-labeled cells significantly increased as compared respectively with the 14-day control （C-14d group） and the 28-day control （C-28d） group （P〈0.05 or P〈0.01）. Conclusions： EA at the Conception Vessel promotes differentiation and proliferation of the nerve stem cells in the inferior zone of the lateral ventricle in the cerebral ischemia rats, and may stimulate differentiation of the proliferous nerve stem cells towards the astrocvtes.

Effects on Proliferation and Migration of the Human Colon Carcinoma Cell Line SW620 by Silencing of Hepatocyte Growth Factor Expression

OBJECTIVE Hepatocyte growth factor （HGF） expression is closely related to the progression and poor prognosis of colorectal cancer patients. In this study, we investigated the effects on proliferation and migration of the human colon carcinoma cell line SW620 by silencing HGF expression. METHODS HGF was silenced using specific HGF a/f3 siRNA. The proliferation, migration, cell cycle and ultrastructure of SW620 cells were examined. RESULTS The transfection efficiency was 70%-80%. The expression rate of HGF in the experimental group was significantly lower than that in the negative and blank control groups （P 〈 0.05）. The proliferation inhibition rate in the experimental group at 24, 48, 72 and 96 h after transfection was 14.2%, 50.2%, 39.5% and 23.2%, respectively. The migratory ability of cells in the experimental group was significantly inhibited compared with that in the negative control or blank control groups （58.2% vs. 2.1% or 0%, P 〈 0.05）. CONCLUSION The application of RNA interference to silence the expression of HGF in the colon carcinoma cell line SW620 effectively inhibits the proliferation and migration of tumor cells.

Effectof the Local Strain CN5 of Human Herpesvirus 6 on CD Molecule Expression and PHA-Induced Proliferation of Cord Blood or Peripheral Blood Mononuclear Cells

Cord blood mononuclear cells (CBMC's) and adult peripheral blood mononuclear cells (PBMCs), cultured with RPMI 1640 medium containing 20% fetal calf serum plus 5 mg/L PHA and 10 mg/L IL-Z, were inoculated with CN5 strain of human herpesvirus 6 (HHV 6 ) isolated from a Chinese patient with exanthem subitum and the CN5 infected cell lysates were added to cultures of CBMCs and PBMCs, so as to observe the effects of the local strain CN5 on expression of CD molecule or on proliferation of mononuclear cells by the methods of APAAP staining and MTT assay.The results were as follows: ①Expressions of some CD antigens of CBMCs and PBMCs could change after CN5 strain infection. In both cases, CD3 expresion was down-regulated while CD4 expression was up-regulated. There were no significant differences of CD2, CD8 and CD45RA expressions between the two groups with and without CN5 infection. But the ratio of CD4 to CD8 sigmificantly rose because of the increasing of CD4 positiveity. ②The lysates of CB5-infected CBMCs inhibited the liferation of PBMCs, not of CBMCs, in a protein concentration-dependent pattern. This inhibition was partially neutralized by specific antiserum to CN5, not by antisera to INF-α and TNF-α.

Effects of β-TCP Ceramics on Osteoblast Cellular Proliferating,Mineralization and Osteocalcin Expression

After co-cultrured osteoblast with fl-TCP ceramics, the cellular proliferating, mineralization and osteocalcin expression were studied. MTT assay showed that fl-TCP ceramics had no affect on cellular proliferating. Laser scanning confocal detection showed that fl-TCP ceramics could increase the mineralization level of osteoblast. Furthermore, RT-PCR showed that fl-TCP could increase the expression level of osteocalcin. Those results indicate β-TCP ceramics had perfect biocompatibility and increased the mineralization of osteoblast to accelerate osteogenesis by means of affecting the expression of genes involving in osteogeneticprocess.

Flow Cytometry Analysis of Cellular DNA Content of the Parotid Pleomorphic Adenoma

The nuclear DNA content in 42 cases of primary parotid pleomorphic adenoma (PPA) and 15 cases of recurrent PPA were analysed with flowcytometer (FCM) to study the correlation of the DNA index (DI), S% and cellular proliferous index (PI) with the biologic behaivor of the tumor. The results indicated that in a portion of pleomorphic adenoma, the nuclear DNA content had altered and possessed malignant potential before any evidence of malignancy could be found under lightmicroscope. The increase of S% and PI, which followed the course of tumor development, has a close relation with the capsular invasion and the recurrence. There was a significant difference on the DI, S%, PI as well as the incidence of heteroploid between the recurrent and the incipient tumor. A great portion of recurrent tumors, which still diagnosed as benign pathologically, was acually heteroploid.

Gene expression profiling reveals Ki-67 associated proliferation signature in human glioblastoma

Background Everlasting cellular proliferation is the fundamental feature during gliomagenesis and Ki-67 is one of the classical proliferation markers in human glioblastoma multiforme （GBM）. However, the driver genes or core pathways for cellular proliferation in GBM have not been elucidated systematically. Methods We evaluated by immunohistochemistry the prognostic value of Ki-67 expression in the clinical outcome of 156 Chinese patients with GBM and a total of 64 GBM samples were selected for further Agilent genome-wide microarray analysis. On the basis of the microarray data from Tiantan （n--64） and The Cancer Genome Atlas （TCGA） （n=202） database, differentially expressed genes between the GBM subgroups with high or low level of Ki-67 expression were identified using Significance Analysis of Microarrays （SAM）. Gene Ontology （GO） and KEGG Pathway analyses were then undertaken for the Ki-67 associated genes to identify the most significant biological processes and signaling pathways. Results We confirmed that Ki-67 was an independent prognostic indicator in the largest Chinese patient cohort of 156 GBM samples via immunohistochemical staining. Survival analysis of Ki-67 over-expression revealed a highly significant association with a worse clinical outcome （P=0.010 for progression-free survival; P=0.007 for overall survival）. Comparative and integrated analysis between -Iqantan and TCGA database identified a 247-gene ＂proliferation signature＂ （205 up-regulated and 42 down-regulated genes） that distinguished Ki-67 expression phenotypes. GO and KEGG Pathway analyses further indicated that Ki-67 expression phenotype was associated with distinct changes in gene expression associated with the regulation of cellular growth and proliferation. Conclusions Proliferation marker Ki-67 is an independent prognostic indicator in Chinese GBM patients. And Ki-67 associated proliferation signature identified through genome-wide microarray analysis may provide potential targets for anti-proliferation therapy in GBM.

Keratinocyte growth factor phage model peptides can promote epidermal cell proliferation without tumorigenic effect

Background Keratinocyte growth factor （KGF） significantly influences epithelial wound healing. The aim of this study was to isolate KGF phage model peptides from a phage display 7-mer peptide library to evaluate their effect on promoting epidermal cell proliferation. Methods A phage display 7-mer peptide library was screened using monoclonal anti-human KGF antibody as the target. Enzyme linked immunosorbent assay （ELISA） was performed to select monoclonal phages with good binding activity. DNA sequencing was done to find the similarities of model peptides. Three-（4,5-dimethylthiazol-2-yl） -2,5-diphenyl tetrazolium bromide （MTT） assay, immunofluorescence assay and quantitative real-time PCR analysis were employed to evaluate the effect of the phage model peptides on epidermal cells. Results Thirty-three out of fifty-eight （56.9%） of the isolated monoclonal phages exhibited high binding activity by ELISA. Ten of fifteen obtained phage model peptides were similar to KGF or epidermal growth factor （EGF）. MTT assay data showed that four （No. 1-4） of the ten phage model peptides could promote epidermal cell proliferation. The expression of keratinocyte growth factor receptor （KGFR） mRNA in the KGF control group and the two phage model peptide groups （No. 1 and No. 2） increased. Expression of c-Fos mRNA and c-Jun mRNA in the KGF control group increased, but did not increase in the four phage model peptide groups （No.1-4）. Conclusion Four phage model peptides isolated from the phage display 7-mer peptide library can safely promote epidermal cell proliferation without tumorigenic effect.

Cell competition and its implications for development and cancer

Cell competition is a struggle for existence between cells in heterogeneous tissues of multicellular organisms. Loser cells, which die during cell competition, are normally viable when grown only with other loser cells, but when mixed with winner cells, they are at a growth disadvantage and undergo apoptosis. Intriguingly, several recent studies have revealed that cells bearing mutant tumor-suppressor genes, which show overgrowth and tumorigenesis in a homotypic situation, are frequently eliminated, through cell competition, from tissues in which they are surrounded by wild-type cells. Here, we focus on the regulation of cellular competitiveness and the mechanism of cell competition as inferred from two different categories of mutant cells： （1） slower-growing cells and （2） structurally defective cells. We also discuss the possible role of cell competition as an intrinsic homeostasis system through which normal cells sense and remove aberrant cells, such as precancerous cells, to maintain the integrity and normal development of tissues and organs.