No abstract available.
Up-Regulation*

p11 protein (S100A10) is downregulated in depressive-like states of human and rodent. Antidepressant drug treatment increases p11 levels in rodent models. We reviewed studies demonstrating that p11 levels are regulated in depression and by antidepressant treatment and that p11 upregulation exerts antidepressant effects. Current studies on p11 underscore the importance of p11 as a potential antidepressant target.
Depression* ; Humans ; Rodentia ; Up-Regulation

No abstract available.
Animals ; Hyperalgesia ; Microglia ; Rats ; Up-Regulation

OBJECTIVETo investigate the whole genome expression profiles between gastric high-grade intraepithelial neoplasia (HGIN) tissues with cancer and HGIN tissues without cancer.

METHODSGastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected at Peking Union Medical College Hospital from March 2010 to May 2013. Each of the forceps biopsies from the 21 patients was HGIN,but there were 10 HGIN and 11 HGIN with cancer after the endoscopic submucosal dissection. The whole genome expression profiling was performed on 10 HGIN samples and 11 HGIN with cancer samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology(GO)enrichment analysis was performed using the GeneSpring software GX 12.6.

RESULTSThe gene expression patterns were different between HGIN tissues with cancer and HGIN tissues without cancer. There were 470 significantly differentially expressed transcripts between them (P<0.05,Fold Change>2), with 180 up-regulated genes and 290 down-regulated genes in HGIN tissues with cancer. A GO enrichment analysis demonstrated that the most striking over-expressed transcripts in HGIN with cancer were in the category of triglyceride biosynthetic process,acylglycerol biosynthetic process,neutral lipid biosynthetic process,glycerol ether metabolic process,organic ether metabolic process,and glycerolipid metabolic process.

CONCLUSIONThe change of lipid metabolism may contribute to the pathogenesis of gastric cancer at an early stage.

Algorithms ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Lipid Metabolism ; Software ; Stomach Diseases ; Stomach Neoplasms ; Up-Regulation

OBJECTIVETo examine the micro-RNA (mirna) expression profile in tissues of early gastric cancer and to screen the specific mirna associated with gastric cancer.

METHODSGene chip technology was used to detect the expression of mirna in early gastric cancer tissues and adjacent normal tissues.

RESULTSCompared to adjacent normal tissues, a total of 36 mirnas were down-regulated, such as mir-9-1, mir-103 and mir-141, while 12 mirnas were up-regulated, such as mir-196a, mir-142-3p and mir-25, etc.

CONCLUSIONAbnormal mirna expression level in early gastric cancer tissues may be associated to the development of gastric cancer.

Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; Oligonucleotide Array Sequence Analysis ; Stomach Neoplasms ; genetics ; Up-Regulation

PURPOSE: The purpose of this study is to analyze the mechanism of RECK gene (a novel MMP inhibitor) in human osteosarcoma and evaluation of RECK as a prognostic factor and therapeutic target. MATERIALS AND METHODS: Osteosarcoma cell lines were established from tumor samples of 23 patients who had been treated from March 2003 to April 2004 and 4 standard cell lines (HOS, MG-63, SaOS-2, U-2OS). We isolated the RNA from 27 cell lines and evaluated the expression level of RECK gene using quantitative real time-PCR method. MMP-2 and MMP-9 expression were evaluated by gelatin zymography. Five cell lines were selected which had a statistical significance between RECK gene up-regulation and MMP expression (p=0.01). Then 5 cell lines and 3 standard cell lines were transfected by RECK gene. We compared RECK gene expression with MMP down-regulation between transfected cell lines and non-transfected cell lines. Invasion of transfected cell lines were evaluated by invasion assay using matrigel. RESULTS: RECK genes were expressed in all cell lines and 1 cell line showed especially high expression. In zymography, pro-MMP-2 was expressed in almost cell lines whereas pro-MMP-9 was rarely expressed. RECK gene expressions were increasingly high and MMP expressions were low in transfected cell lines via zymography. Transfected HOS cells decreased invasiveness in matrigel invasion assay and showed small number of migrated cells. It had a statistical significance (p<0.01). CONCLUSION: It is expected that down-regulation of MMP by RECK gene expression can be used as a biologic marker. It can be a new therapeutic strategies and valuable prognostic factors in treating osteosarcoma.
Biomarkers ; Cell Line ; Down-Regulation ; Gelatin ; Gene Expression ; Humans ; Osteosarcoma* ; RNA ; Transfection ; Up-Regulation

BACKGROUND: UVB irradiation induces apoptosis or/and autophagy through several molecular pathways in keratinocytes. However, the precise molecular mechanism of UVB-induced autophagy is largely unknown in keratinocytes. OBJECTIVE: The purpose of this study was to investigate the molecular mechanisms of UVB-induced apoptosis and autophagy in HaCaT cell lines. METHODS: Cells were irradiated by UVB (Westinghouse FS-40 sunlamps) with various doses (0, 30, 60, 120, 240 mJ/cm2). The expression levels of caspase-3, Bax, Bcl2, Bcl-X(L) and LC3 were confirmed by Western blot analysis in UVB-irradiated HaCaT cell lines. Apoptotic cells were analyzed by PI staining, and autophagy cells were analyzed by immunofluorescent staining. RESULTS: The expression of Bcl-X(L) decreased from UVB 60 mJ/cm2 and Bcl2 decreased from UVB 240 mJ/cm2. The expression of caspase-3 was increased from UVB 120 mJ/cm2. These data showed that UVB-induced apoptosis is mediated by up-regulation of caspase-3 and down-regulation of Bcl2 and Bcl-X(L). Furthermore, the expression of LC3 increased from UVB 120 mJ/cm2. In addition, autophagy formation was observed in few fractions of apoptotic HaCaT cells in immunofluorescent staining; most apoptotic cells did not show autophagy formation. Moreover, autophagy formation inhibitor treatment induced a slight increment of apoptotic cell population under UVB irradiation. CONCLUSION: UVB irradiation induces not only apoptotic cell death but also autophagy formations; these events may create a defense mechanism for the prevention of apoptosis in UVB-treated HaCaT cells.
Apoptosis ; Autophagy ; Blotting, Western ; Caspase 3 ; Cell Death ; Cell Line ; Down-Regulation ; Keratinocytes ; Up-Regulation

Osteocytes may function as mechanotransducers by regulating local osteoclastogenesis. Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Receptor activator of nuclear factor-kappaB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. The hypoxia induced osteoclastogenesis via increased RANKL expression in osteoblasts was demonstrated. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. In the present study, we investigated whether hypoxia regulates RANKL expression in murine osteocytes and HIF-1alpha mediates hypoxia-induced RANKL expression by transactivating RANKL promoter, to elucidate the role of osteocyte in osteoclastogenesis in the context of hypoxic condition. The expression levels of RANKL mRNA and protein, as well as hypoxia inducible factor-1alpha (HIF-1alpha) protein, were significantly increased in hypoxic condition in MLO-Y4s. Constitutively active HIF-1alpha alone significantly increased the levels of RANKL expression in MLO-Y4s under normoxic conditions, whereas dominant negative HIF-1alpha blocked hypoxia-induced RANKL expression. To further explore to find if HIF-1alpha directly regulates RANKL transcription, a luciferase reporter assay was conducted. Hypoxia significantly increased RANKL promoter activity, whereas mutations of putative HIF-1alpha binding elements in RANKL promoter prevented this hypoxia-induced RANKL promoter activity in MLO-Y4s. These results suggest that HIF-1alpha mediates hypoxia-induced up-regulation of RANKL expression, and that in osteocytes of mechanically unloaded bone, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in osteocytes.
Anoxia* ; Bone Development ; Gene Expression Regulation ; Luciferases ; Osteoblasts ; Osteocytes* ; Oxygen ; RANK Ligand* ; RNA, Messenger ; Up-Regulation

PURPOSE: The purpose of this study was to evaluate the expressions of KAI-1 and survivin, and to investigate their correlation with the clinical stage and survival rate of patients with ovarian carcinomas. MATERIALS AND METHODS: The expressions of survivin and KAI-1 were immunohistochemically determined in 54 serous and mucinous ovarian adenocarcinomas and borderline malignancy tumors. 10 of the 54 cases were also analyzed for the expressions of survivin and KAI-1 using western blot. RESULTS: The down-regulation of the expression of KAI-1 was observed by immunohistochemical staining (IHC) in 53.7% of the ovarian cancers, and a negative reaction in 50% by the western blot analysis. From the IHC, the survivin expression was positive and strongly positive in 51.9 and 18% of the ovarian cancers, respectively. From the western blot analysis, 10% of the ovarian cancer showed positive reactions. The down- regulation of the KAI-1 expression was significantly correlated with the clinical stage (p=0.001) and disease free survival rate (p<0.001), but not with the histological type. The expression of survivin was not correlated with the clinical stage or histological type. However, the patients with a negative survivin expression had a significantly longer disease survival rate than those with a strong positive expression. CONCLUSION: The down- and up-regulation of the KAI-1 and survivin, respectively, might be independent prognostic factors in human ovarian carcinomas.
Adenocarcinoma ; Blotting, Western ; Disease-Free Survival ; Down-Regulation ; Humans ; Mucins ; Ovarian Neoplasms ; Survival Rate ; Up-Regulation

The role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the lead (Pb)-induced cellular response was investigated in the cultured endothelial cells. Pb caused progressive cellular death in endothelial cells, which occurred in a concentration- and time-dependent manner. However, Ref-1 overexpression with AdRef-1 significantly inhibited Pb-induced cell death in the endothelial cells. Also the overexpression of Ref-1 significantly suppressed Pb-induced superoxide and hydrogen peroxide elevation in the endothelial cells. Pb exposure induced the downregulation of catalase, it was inhibited by the Ref-1 overexpression in the endothelial cells. Taken together, our data suggests that the overexpression of Ref-1 inhibited Pb-induced cell death via the upregulation of catalase in the cultured endothelial cells.
Catalase ; Cell Death ; Down-Regulation ; Endothelial Cells ; Hydrogen Peroxide ; Superoxides ; Up-Regulation