PubMed Health⌕ Search

Biomedical subjects

Ying Shan

Publications and source records attributed to Ying Shan.

17 recordsLinked to original sources
PubMed2006

Role of Bach1 and Nrf2 in up-regulation of the heme oxygenase-1 gene by cobalt protoporphyrin.

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin with the release of iron and carbon monoxide. HO-1 is highly inducible by a large number of physical and chemical factors. CoPP is known to be a potent and effective inducer of HO-1 activity in many tissues. Here we report that CoPP up-regulates HO-1 via Bach1 and Nrf2 in human liver cells. CoPP did not influence hepatic Bach1 or Nrf2 mRNA levels, but markedly reduced Bach1 protein levels by increasing degradation of Bach1 protein (t(1/2) from 19 h to 2.8 h), and increased Nrf2 by decreasing degradation of Nrf2 protein (t(1/2) from 2.5 h to 9 h). Silencing Bach1 by Bach1-siRNA significantly increased levels of HO-1 mRNA and protein, and addition of CoPP up-regulated HO-1 mRNA and protein further. However, silencing Nrf2 mRNA by Nrf2-siRNA did not significantly change baseline HO-1 mRNA or protein levels, but significantly decreased 5-10 microM CoPP-mediated up-regulation of HO-1 mRNA levels compared with CoPP alone. Transfection with equal amounts of non-Bach1 or non-Nrf2 related control siRNA did not reduce Bach1 or Nrf2 mRNA or protein, confirming the specificity of Bach1- and Nrf2-siRNA in Huh-7 cells. We conclude that the pathway of CoPP-mediated induction of HO-1 involves the repression of Bach1 and up-regulation of the Nrf2 protein by post-transcriptional site(s) of action. Because CoPP, unlike heme, is neither a prooxidant nor a substrate for HO-1, it might be considered as a potential therapeutic agent in situations where up-regulation of HO-1 is desired.

Basic-Leucine Zipper Transcription Factors↗
PubMed2006

Cell cycle-controlled interaction of nucleolin with the retinoblastoma protein and cancerous cell transformation.

Retinoblastoma protein (Rb) is a multifunctional tumor suppressor, frequently inactivated in certain types of human cancer. Nucleolin is an abundant multifunctional phosphoprotein of proliferating and cancerous cells, recently identified as cell cycle-regulated transcription activator, controlling expression of human papillomavirus type 18 (HPV18) oncogenes in cervical cancer. Here we find that nucleolin is associated with Rb in intact cells in the G1 phase of the cell cycle, and the complex formation is mediated by the growth-inhibitory domain of Rb. Association with Rb inhibits the DNA binding function of nucleolin and in consequence the interaction of nucleolin with the HPV18 enhancer, resulting in Rb-mediated repression of the HPV18 oncogenes. The intracellular distribution of nucleolin in epithelial cells is Rb-dependent, and an altered nucleolin localization in human cancerous tissues results from a loss of Rb. Our findings suggest that deregulated nucleolin activity due to a loss of Rb contributes to tumor development in malignant diseases, thus providing further insights into the molecular network for the Rb-mediated tumor suppression.

Cell Cycle↗
PubMed2006

HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells.

BACKGROUND/AIMS: Hepatitis C infection induces hepatic oxidative stress. Heme oxygenase (HO), the rate-controlling enzyme of heme catabolism, plays a key role as a protector against oxidative, and other stresses. Other recent work has implicated Bach1, a heme binding protein that represses gene expression, in the regulation of HO-1 gene expression. METHODS: We investigated the effects of HCV polyprotein expression on expression of HO-1 and Bach1 genes in human hepatoma cells (Huh-7 cells). RESULTS: HO-1 was up-regulated in the cell line expressing HCV proteins from core up to the aminoterminal domain of NS3. Addition of increasing concentrations of N-acetylcysteine (NAC) led to down-regulation of HO-1 in cells expressing HCV proteins. In contrast, Bach1 was significantly down-regulated in these cells. Sodium arsenite, a strong inducer of oxidative stress and HO-1, reduced Bach1 expression in wild type Huh-7 cells, and NAC partially abrogated this decrease. CONCLUSIONS: Huh-7 cells expressing HCV proteins show significant up-regulation of the HO-1 gene, and reciprocal down-regulation of the Bach1 gene. Exogenous oxidative stressors and anti-oxidants can modulate expression of these genes. These and other results suggest a key role of down-regulation of Bach1 and up-regulation of HO-1 in diminishing cytotoxic effects of HCV proteins in human hepatocytes.

Basic-Leucine Zipper Transcription Factors↗
PubMed2006

Rapid object indexing using locality sensitive hashing and joint 3D-signature space estimation.

We propose a new method for rapid 3D object indexing that combines feature-based methods with coarse alignment-based matching techniques. Our approach achieves a sublinear complexity on the number of models, maintaining at the same time a high degree of performance for real 3D sensed data that is acquired in largely uncontrolled settings. The key component of our method is to first index surface descriptors computed at salient locations from the scene into the whole model database using the Locality Sensitive Hashing (LSH), a probabilistic approximate nearest neighbor method. Progressively complex geometric constraints are subsequently enforced to further prune the initial candidates and eliminate false correspondences due to inaccuracies in the surface descriptors and the errors of the LSH algorithm. The indexed models are selected based on the MAP rule using posterior probability of the models estimated in the joint 3D-signature space. Experiments with real 3D data employing a large database of vehicles, most of them very similar in shape, containing 1,000,000 features from more than 365 models demonstrate a high degree of performance in the presence of occlusion and obscuration, unmodeled vehicle interiors and part articulations, with an average processing time between 50 and 100 seconds per query.

Algorithms↗
PubMed2006

Shapeme histogram projection and matching for partial object recognition.

Histograms of shape signature or prototypical shapes, called shapemes, have been used effectively in previous work for 2D/3D shape matching and recognition. We extend the idea of shapeme histogram to recognize partially observed query objects from a database of complete model objects. We propose representing each model object as a collection of shapeme histograms and match the query histogram to this representation in two steps: 1) compute a constrained projection of the query histogram onto the subspace spanned by all the shapeme histograms of the model and 2) compute a match measure between the query histogram and the projection. The first step is formulated as a constrained optimization problem that is solved by a sampling algorithm. The second step is formulated under a Bayesian framework, where an implicit feature selection process is conducted to improve the discrimination capability of shapeme histograms. Results of matching partially viewed range objects with a 243 model database demonstrate better performance than the original shapeme histogram matching algorithm and other approaches.

Algorithms↗
PubMed2006

[Effect of carbon monoxide and nitric oxide on the apoptosis of hippocampal neurons in rats with febrile seizures].

OBJECTIVE: Febrile seizure (FS) is the most common type of seizure disorders in children. Recurrent FS can cause hippocampal neurons injury. At the same time heme oxygenase/carbon monoxide (HO/CO) system and nitric oxide synthase/nitric oxide (NOS/NO) system were up-regulated and interacted each other. This study examined the effects of the two systems on the apoptosis of hippocampal neurons in rats with recurrent FS. METHODS: FS was induced in rats by exposure to warm water bath (45.2 degrees C), once every 2 days, 10 times in all. Sprague-Dawley (SD) rats aged 21 days were randomly assigned into four groups: Control (37 degrees C water bath exposure), FS, FS + ZnPP-IX (HO inhibitor) and FS + L-NAME (NOS inhibitor) groups. The apoptosis of hippocampal CA1 neurons was detected by TUNEL. RESULTS: After recurrent FS, the apoptotic cells in the hippocampal CA1 neurons increased by 225% compared with those in the Control group (P < 0.01). The apoptotic cells in the FS+ZnPP-IX group increased by 62% and 425% compared with those in the FS and the Control groups (both P < 0.01). The apoptotic cells in the FS + L-NAME group decreased by 38% compared with those in the FS group (P < 0.01) and increased by 100% compared with those in the Control group (P < 0.05). CONCLUSIONS: In recurrent FS, exogenous administration of HO inhibitor ZnPP-IX may induce an increase of apoptotic cells in hippocampal neurons, while NOS inhibitor L-NAME may decrease the apoptotic cells. The results suggest that the HO/CO system might alleviate neuronal damage, while NOS/NO system might augment neuronal damage.

Animals↗
PubMed2006

[Clinical evaluation of high-risk HPV detection by hybrid capture II in screening cervical intraepithelial neoplasma].

OBJECTIVE: To evaluate the value of high-risk HPV (hrHPV) detection by Hybrid Capture II (HC2) in screening cervical intraepithelial neoplasm (CIN). METHODS: Totally 723 patients who had received a dual screening with thinprep cytologic test (TCT) and HC2 in our department were analyzed retrospectively. Among them, 350 patients received a triple examination with TCT, HC2, and colposcopic biopsy. RESULTS: Among the 723 patients, the incidences of hrHPV infection with atypical squamous cell (ASC), low squamous intraepithelial lesion, and high squamous intraepithelial lesion were 70.7% (94/133), 88.9% (249/280), and 90.9% (90/99), respectively, significantly higher than 55.5% (117/211), the incidence of hrHPV infection with normal cytological results (P = 0.005, P < 0.001, P < 0.001, respectively). Among 350 cases who were received triple examination, the incidence of hrHPV infection with cervical intraepithelial neoplasia (CIN) 1 and CIN 2 were 88.9% (72/81) and 96.3% (52/54), significantly higher than 77.7% (153/197), the incidence of hrHPV infection with normal pathological results (P = 0.03, P = 0.002); The incidence of hrHPV infection with CIN 3 and squamous cancer were 91.7% (11/12) and 100.0% (6/6), also higher than normal cases. Among these 350 cases, the incidence of hrHPV infection with ASC was 79.3% (69/87). The incidence of CIN 2-3 with ASC and hrHPV infection was 38.0%, significantly higher than the incidence of CIN 2-3 with ASC and without hrHPV infection (5.9%) (P = 0.04). CONCLUSION: hrHPV infection has a close relation with CIN, and the incidence of hrHPV infection increases along with the severity of CIN.

Adolescent↗
PubMed2005

Association of hepatitis C virus infection with serum iron status: analysis of data from the third National Health and Nutrition Examination Survey.

BACKGROUND: There is growing evidence that mildly increased amounts of iron in the liver can increase hepatic injury, particularly if combined with other hepatotoxic factors, such as alcohol use, use of porphyrogenic drugs, or chronic viral hepatitis. In the present study, the association of hepatitis C virus (HCV) infection with serum measurements of iron status was assessed in the US population. METHODS: We analyzed data from a total of 14,462 participants in the Third National Health and Nutrition Examination Survey. We excluded subjects who were aged <12 years, subjects for whom measurements of serum levels of iron or ferritin or the results of liver function tests were missing, and subjects who had a serum transferrin saturation of > or =50% (to help exclude subjects with hemochromatosis). RESULTS: Mean serum levels of ferritin and iron (+/- standard error) were significantly higher among subjects with HCV infection (100+/-3 ng/mL and 229+/-17 microg/dL, respectively) than among subjects without liver disease (83+/-0.3 ng/mL and 101+/-2.1 microg/dL, respectively) (P<.0001). Serum levels of ferritin were directly and significantly correlated with serum levels of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase (r=0.25, r=0.24, and r=0.28, respectively; P<.0001), whereas platelet counts were inversely correlated with serum levels of ferritin (r=-0.12; P<.0001). CONCLUSION: HCV infection is significantly associated with higher serum levels of ferritin and iron in the US population.

Adolescent↗
PubMed2004

Role of Bach-1 in regulation of heme oxygenase-1 in human liver cells: insights from studies with small interfering RNAS.

Heme oxygenase-1 is an antioxidant defense enzyme that converts heme to biliverdin, iron, and carbon monoxide. Bach-1 is a bZip protein that forms heterodimers with small Maf proteins and was reported recently to down-regulate the HO-1 gene in mice. Using small interfering RNAs targeted to human Bach-1 mRNA, we investigated whether modulation of human hepatic Bach-1 expression by small interfering (si)RNA technology influences heme oxygenase-1 gene expression. We found that Bach-1 siRNAs transfected into Huh-7 cells significantly reduced Bach-1 mRNA and protein levels approximately 80%, compared with non siRNA-treated cells. In contrast, transfection with the same amounts of nonspecific control duplexes or LaminB2-duplex did not reduce Bach-1 mRNA or protein levels, confirming the specificity of Bach-1 siRNA. Expression of the heme oxygenase-1 gene in Bach-1 siRNA-transfected cells was up-regulated 7-fold, compared with cells without Bach-1 siRNA. The effect of increasing concentrations of heme to up-regulate levels of heme oxygenase-1 was more pronounced when Bach-1 siRNA was present. Taken together, these results indicated that Bach-1 has a specific and selective ability to repress expression of human hepatic heme oxygenase-1. Silencing of Bach-1 by siRNAs is a useful method for up-regulating HO-1 gene expression. Exogenous heme produces additional up-regulation, beyond that produced by Bach-1 siRNAs, suggesting that heme does not act solely through its effects on Bach-1.

Animals↗
PubMed2004

Identification of key elements that are responsible for heme-mediated induction of the avian heme oxygenase-1 gene.

UNLABELLED: Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin with the release of iron and carbon monoxide. HO-1 is highly inducible by a large number of physical and chemical factors. In recent work, we had identified a metalloporphyrin-responsive element (MPRE) that localized at -3.7 kb upstream of the transcription start site of the chick HO-1 gene. Here, we identify four additional heme-responsive elements (HeREs), which are "expanded" AP-1 sites, in the 5'-flanking region of the chick HO-1 gene. These sites, located at -4675, -4599, -3660, and -3625 bp from the transcription start site of the gene, were necessary and sufficient for up-regulation of luciferase reporter gene expression in the presence of heme and cobalt protoporphyrin (CoPP), but not several other metalloporphyrins. Site-directed mutagenesis was carried out using pcHO7.1Luc or pcHO7.1-4.6Luc as templates. Single and multiple mutations of HeREs and MPRE significantly abrogated the heme- and CoPP-dependent up-regulation of reporter gene expression in transient or stable transfection experiments. CONCLUSIONS: The chick HO-1 promoter region contains "expanded" AP-1 sites that are important for up-regulation of the gene by heme and CoPP, but not other metalloporphyrins. These key regulatory elements consist of consensus AP-1 binding sites that have been extended by three base pairs.

Animals↗
PubMed2004

Nucleocytoplasmic shuttling by nucleoporins Nup153 and Nup214 and CRM1-dependent nuclear export control the subcellular distribution of latent Stat1.

Interferon stimulation of cells leads to the tyrosine phosphorylation of latent Stat1 and subsequent transient accumulation in the nucleus that requires canonical transport factors. However, the mechanisms that control the predominantly cytoplasmic localization in unstimulated cells have not been resolved. We uncovered that constitutive energy- and transport factor-independent nucleocytoplasmic shuttling is a property of unphosphorylated Stat1, Stat3, and Stat5. The NH(2)- and COOH-terminal Stat domains are generally dispensable, whereas alkylation of a single cysteine residue blocked cytokine-independent nuclear translocation and thus implicated the linker domain into the cycling of Stat1. It is revealed that constitutive nucleocytoplasmic shuttling of Stat1 is mediated by direct interactions with the FG repeat regions of nucleoporin 153 and nucleoporin 214 of the nuclear pore. Concurrent active nuclear export by CRM1 created a nucleocytoplasmic Stat1 concentration gradient that is significantly reduced by the blocking of energy-requiring translocation mechanisms or the specific inactivation of CRM1. Thus, we propose that two independent translocation pathways cooperate to determine the steady-state distribution of Stat1.

3T3 Cells↗
PubMed2004

[Effect of naloxone on remote seizure susceptibility].

OBJECTIVE: To evaluate the effect of low dose naloxone on remote seizure susceptibility after repeated febrile seizures(FS) in developing age. METHODS: Warm water induced rat FS model was developed in this study. Forty-nine SD rats were randomly divided into two groups: normal control group(n=10) and hyperthermic seizure group (n=39). The latter was further divided into FS control group (n=13) and naloxone-treated group (n=26). The dose of naloxone was different in the two naloxone-treated groups (13/each group). One group dose was 1 mg/kg, and the other 2 mg/kg. Each rat of hyperthermic seizure groups was induced to have 7 febrile seizures at the interval of 1 day. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of other groups were injected with 0.9% sodium chloride. After the seventh stimulation, all rats were left un-stimulated for 2 months, then re-stimulated. Re-stimulated seizure incidence rate, seizure duration and seizure grade in different groups were observed and compared with each other. Hippocampal mossy fiber sprouting was detected by Timm stain. RESULTS: In naloxone-treated group, the rats' seizure duration and seizure grade [(5.66+/-2.78) min, (2.97+/-1.18)] significantly decreased (t=5.035, P<0.01; t=3.343, P<0.01) compared with those in FS control group [(21.18+/-4.06) min, (4.54+/-0.78)], although no significant gap was observed on seizure incidence rate(57.7%,84.6% respectively) and seizure latency between them. In non-treated group, in which two rats developed status epilepsy, the incident rate of the fifth grade seizure was 69.3%, much higher than 19.3% of naloxone treated group. Timm-stain pattern showed that the straining in the IML (inner molecular layer) of treated group rats was much lighter than that of non-treated group [(2.33+/-1.03), (0.92+/-0.79), P<0.01]. CONCLUSION: Low dose naloxone used on naive rat with repeated febrile seizures can efficiently decrease the seizure susceptibility in the mature period and lighten the neural damage by twice-hit seizure in the mature period as well.

Animals↗
PubMed2004

[Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure].

OBJECTIVE: The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children. So how to decrease the related damage is a very important issue. The main purpose of the present study was to find out whether the non-specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure-induced brain damage. METHODS: Warm water induced rat FS model was developed in this study. Forty-seven rats were randomly divided into two groups: normal control group (n = 10) and hyperthermic seizure groups (n = 37). The latter was further divided into FS control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone is different in two naloxone-treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of the other groups were injected with 0.9% sodium chloride. Latency, duration and grade of FS in different groups were observed and compared. HE-staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons. RESULTS: In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/- 0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P < 0.01; t = 8.439, P < 0.01) than those in FS control group (7.70 +/- 2.25 min, 4.52 +/- 0.49), although no significant gap was observed on FS latency between them. In FS control group, HE-staining pattern of hippocampal CA(1) and CA(2) showed lots of disordered neurons with confused polarity and vacuoles formed. Nuclei were with various size, some rounded and some oblong. While in naloxone-treated groups, the arrangement of neurons was regular, only a small quantity of neurons had changed polarity and vacuoles formed. Most nuclei were oblong and in the same size. In hippocampal CA(1) region and dentate gyrus of rats from FS control group, EM showed that the most mitochondrion volumes obviously increased with vacuoles formed, the matrix condensed, the ridge obscured or disappeared, apoptosis body emerged. Minor to moderate dilation of rough endoplasmic reticulum and Golgi's complex was also observed. However, in naloxone-treated groups, the number of neurons with swollen mitochondrion and endoplasmic reticulum was much fewer than that in FS control group. No apoptosis body was observed. The comparison between them showed much lighter brain damage in naloxone-treated groups than in FS control group. CONCLUSION: Although low-dose naloxone could not totally stop the occurrence of febrile seizure, it could lighten the brain damage resulted from repeated FS to some extent.

Animals↗
PubMed2003

Iron as a co-morbid factor in nonhemochromatotic liver disease.

Heavy iron overload, in both primary and secondary hemochromatosis, may cause fibrosis of parenchymal organs, especially the liver. The toxicity of iron is believed to involve increased oxidative stress, with iron-catalyzed production of reactive oxygen species causing oxidative damage to lipids, proteins, and nucleic acids. Lesser degrees of hepatic iron deposition are also associated with, and seem to be risk factors for, certain nonhemochromatotic liver diseases. Porphyria cutanea tarda is associated with hepatic iron overload and responds to iron-reduction therapy. Results of recent studies have demonstrated high prevalences (about 60%-80%) of HFE gene mutations in patients with porphyria cutanea tarda. Chronic hepatitis C is another risk factor for porphyria cutanea tarda. Other recent evidence indicates that the prevalence of HFE gene mutations is increased in chronic viral hepatitis and that patients with chronic hepatitis C harboring especially the C282Y mutation are more likely to suffer from advanced hepatic fibrosis or cirrhosis and to do so at younger ages. A role for modest iron overload in increasing severity of alcohol-induced liver disease has been well established from results of experimental studies. However, it is currently unresolved whether mild-to-moderate hepatic iron deposition or heterozygosity for the C282Y mutation plays a role in human alcoholic liver disease or in nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. There is persuasive evidence that iron reduction decreases insulin resistance, and it likely also decreases oxidative stress, two key pathogenic features of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Iron loading has also been described after portosystemic shunts and in end-stage liver disease.

Fatty Liver↗
PubMed2002

Mapping of the chick heme oxygenase-1 proximal promoter for responsiveness to metalloporphyrins.

Heme oxygenase (HO) catalyzes the rate-controlling step of physiologic heme catabolism, namely, the oxidation of the alpha-methene bridge of the macrocycle with formation of CO, Fe, and biliverdin. HO-1, the first isoform of HO to be identified, is highly inducible by a large number of physical and chemical factors. Many of these factors cause oxidative or other stresses to cells. In this work, we have studied the regulation of the chick HO-1 gene, using selected promoter--reporter constructs of the gene transiently or stably transfected into primary cultures of chick embryo liver cells or into the LMH line of chicken hepatoma cells. By use of deletional and mutational analyses, DNase protection, and electromobility shift DNA-binding assays, we identified a heretofore undefined regulatory region in the 5'-UTR of the chick HO-1 gene which confers up-regulation of reporter gene (luciferase) expression in the presence of heme and other selected metalloporphyrins. This new metalloporphyrin-responsive element (MPRE) was localized to a 200-bp region 3.8 to 3.6 kb upstream of the transcription starting point of the chick HO-1 gene. It responded particularly to heme and cobalt protoporphyrin with maximal inductions at 10-15 microM concentrations and 15-18 h of exposure. In contrast, sodium arsenite, a prototypical stress-type inducer of HO-1, led to down-regulation of the reporter gene down stream of MPRE. DNase analysis identified an 18-mer oligonucleotide that was required for the metalloporphyrin response (5'-(-3711)TATTGCAGCTGTGTGGGG-3'). Mutations at any of four sites within this oligonucleotide abrogated the metalloporphyrin-dependent up-regulation of reporter gene expression. Nuclear protein extracts of cells treated with heme or cobalt protoporphyrin showed specific enhanced binding to this 18-mer. We conclude that the chick HO-1 promoter region contains a unique sequence that subserves up-regulation of the gene by metalloporphyrins and propose the name "metalloporphyrin-responsive element" for this sequence.

Animals↗