Biomedical subjects

Qiong Wu

Publications and source records attributed to Qiong Wu.

At least 19 recordsLinked to original sources

PubMed2024

DKK1-SE recruits AP1 to activate the target gene DKK1 thereby promoting pancreatic cancer progression.

Super-enhancers are a class of DNA cis-regulatory elements that can regulate cell identity, cell fate, stem cell pluripotency, and even tumorigenesis. Increasing evidence shows that epigenetic modifications play an important role in the pathogenesis of various types of cancer. However, the current research is far from enough to reveal the complex mechanism behind it. This study found a super-enhancer enriched with abnormally active histone modifications in pancreatic ductal adenocarcinoma (PDAC), called DKK1-super-enhancer (DKK1-SE). The major active component of DKK1-SE is component enhancer e1. Mechanistically, AP1 induces chromatin remodeling in component enhancer e1 and activates the transcriptional activity of DKK1. Moreover, DKK1 was closely related to the malignant clinical features of PDAC. Deletion or knockdown of DKK1-SE significantly inhibited the proliferation, colony formation, motility, migration, and invasion of PDAC cells in vitro, and these phenomena were partly mitigated upon rescuing DKK1 expression. In vivo, DKK1-SE deficiency not only inhibited tumor proliferation but also reduced the complexity of the tumor microenvironment. This study identifies that DKK1-SE drives DKK1 expression by recruiting AP1 transcription factors, exerting oncogenic effects in PDAC, and enhancing the complexity of the tumor microenvironment.

Humans↗

PubMed2006

Hydrogen production from a combination of the water-gas shift and redox cycle process of methane partial oxidation via lattice oxygen over LaFeO3 perovskite catalyst.

A redox cycle process, in which CH4 and air are periodically brought into contact with a solid oxide packed in a fixed-bed reactor, combined with the water-gas shift (WGS) reaction, is proposed for hydrogen production. The sole oxidant for partial oxidation of methane (POM) is found to be lattice oxygen instead of gaseous oxygen. A perovskite-type LaFeO3 oxide was prepared by a sol-gel method and employed as an oxygen storage material in this process. The results indicate that, under appropriate reaction conditions, methane can be oxidized to CO and H2 by the lattice oxygen of LaFeO3 perovskite oxide with a selectivity higher than 95% and the consumed lattice oxygen can be replenished in a reoxidation procedure by a redox operation. It is suggested that the POM to H2/CO by using the lattice oxygen of the oxygen storage materials instead of gaseous oxygen should be possibly applicable. The LaFeO3 perovskite oxide maintained relatively high catalytic activity and structural stability, while the carbonaceous deposits, which come from the dissociation of CH4 in the pulse reaction, occurred due to the low migration rate of lattice oxygen from the bulk toward the surface. A new dissociation-oxidation mechanism for this POM without gaseous oxygen is proposed based on the transient responses of the products checked at different surface states via both pulse reaction and switch reaction over the LaFeO3 catalyst. In the absence of gaseous-phase oxygen, the rate-determining step of methane conversion is the migration rate of lattice oxygen, but the process can be carried out in optimized cycles. The product distribution for POM over LaFeO3 catalyst in the absence of gaseous oxygen was determined by the concentration of surface oxygen, which is relevant with the migration rate of lattice oxygen from the bulk toward the surface. This process of hydrogen production via selective oxidation of methane by lattice oxygen is better in avoiding the deep oxidation (to CO2) and enhancing the selectivity. Therefore, this new route is superior to general POM in stability (resistance to carbonaceous deposition), safety (effectively avoiding accidental explosion), ease of operation and optimization, and low cost (making use of air not oxygen).

Journal Article↗

PubMed2006

Identification of genetic markers to distinguish the virulent and avirulent subspecies of Pantoea stewartii by comparative proteomics and genetic analysis.

Pantoea stewartii subsp. stewartii (Pnss), the causal agent of Stewart's bacterial wilt and leaf blight of maize and sweet corn, is one of the quarantine pathogens in many countries and regions. In contrast, P. stewartii subsp. indologenes (Pnsi), the closely related subspecies of Pnss, is avirulent on these plants. In this study, the protein expression profiles of these two subspecies were compared using two-dimensional gel electrophoresis analysis. Twenty-one unique protein spots consistently detected in Pnss but not in Pnsi were analyzed by mass spectrometry. Some of these Pnss-specific proteins are known to be essential for virulence and survival in host, such as FoxR and HrcJ, which are the key components of iron uptake and Type III secretion systems, respectively. For further genetic analysis, six Pnss-specific proteins were characterized by peptide sequencing. Southern and Northern blot analyses revealed that the differences in protein expression profiles of the two subspecies were either due to the discrepancy at genome level or because of the variations in transcriptional expression. The results provide novel genetic markers to distinguish the two closely related subspecies and may also serve as useful clues for investigation of the genetic basis accounting for their sharp difference in virulence.

Amino Acid Sequence↗

PubMed2006

Disruption of parental-specific expression of imprinted genes in uniparental fetuses.

In mammals, imprinted genes show parental origin-dependent expression based on epigenetic modifications called genomic imprinting (GI), which are established independently during spermatogenesis or oogenesis. Due to GI, uniparental fetuses never develop to term. To determine whether such expression of imprinted genes is maintained in uniparental mouse fetuses, we analyzed the expression of 20 paternally and 11 maternally expressed genes in androgenetic and parthenogenetic fetuses. Four genes of each type were expressed in both groups of fetuses. Furthermore, quantitative analysis showed that expression levels deviated from the presumed levels for some imprinted genes. These results suggest that mechanisms acting in trans between paternal and maternal alleles are involved in the appropriate expression of some imprinted genes.

Alleles↗

PubMed2006

Complementary roles of genes regulated by two paternally methylated imprinted regions on chromosomes 7 and 12 in mouse placentation.

Imprinted genes have prominent effects on placentation; however, there is limited knowledge about the manner in which the genes controlled by two paternally methylated regions on chromosomes 7 and 12 contribute to placentation. In order to clarify the functions of these genes in mouse placentation, we examined transcription levels of the paternally methylated genes, tissue differentiation and development and the circulatory system in placentae derived from three types of bi-maternal conceptuses that contained genomes of non-growing (ng) and fully grown (fg) oocytes. The genetic backgrounds of the ng oocytes were as follows: one was derived from the wild-type (ngWT) and another from mutant mice carrying a 13 kb deletion in the H19 transcription unit including the germline-derived differentially methylated region (H19-DMR) on chromosome 7 (ngDeltach7). Another set of oocytes was derived from mutant mice carrying a 4.15 kb deletion in the intergenic germline-derived DMR (IG-DMR) on chromosome 12 (ngDeltach12). Although placental mass was lower in the ngWT/fg placentae compared with that in the WT placentae, it was recovered in the ngDeltach7/fg placentae, but not in the ngDeltach12/fg placentae. The ngDeltach7/fg placental growth improvement was associated with severe dysplasia such as an expanded spongiotrophoblast layer and a malformed labyrinthine zone. In contrast, the ngDeltach12/fg placentae retained the layer structures with expanded giant cells, but their total masses were smaller with a normal circulatory system in order. Our findings demonstrate that the genes controlled by the two paternally methylated regions, H19-DMR and IG-DMR, complementarily organize placentation.

Animals↗

PubMed2006

DNA Binding and cleavage activity of Ni(II) complex with all-trans retinoic acid.

Absorption, fluorescence spectral, cyclic voltammetry and agarose gel electrophoresis studies have been carried out on the interaction of Ni(II) complex with all-trans retinoic acid ([Ni(RA)(2)(H(2)O)(2)] * H(2)O) with DNA. The results indicate that the [Ni(RA)(2)(H(2)O)(2)] * H(2)O can more effectively promote the cleavage of plasmid DNA than that of all-trans retinoic acid (HRA) and Ni(II) at physiological pH and temperature, which may be one of the reasons why the inhibitory effect of [Ni(RA)(2)(H(2)O)(2)] * H(2)O on the human bladder line EJ cells is much greater than that of retinoic acid. It was found that the process of plasmid DNA cleavage was sensitive to ionic strength and pH, however, these radical scavengers almost had no effect on the DNA cleavage reaction. The above results suggested that the cleavage of plasmid DNA by [Ni(RA)(2)(H(2)O)(2)]* H(2)O did not produce diffusible hydroxyl radicals via the Fenton reaction. The results of UV-absorption studies and fluorescence characterization of the interaction of [Ni(RA)(2)(H(2)O)(2)] * H(2)O with Calf thymus DNA show that the [Ni(RA)(2)(H(2)O)(2)] * H(2)O binds to DNA mainly in an intercalating mode.

Antineoplastic Agents↗

PubMed2006

A case with membranous lupus nephritis developing after a twenty-year remission of membranoproliferative glomerulonephritis.

A 30-year-old woman who showed remission of membranoproliferative glomerulonephritis (MPGN) 20 years previously developed membranous lupus nephritis (MLN). She had photosensitivity, facial erythema, proteinuria of 2.59 g/24 hr, anti-nuclear antibody and anti-ds-DNA antibody. To confirm whether a misdiagnosis of MPGN was made 20 years ago, the clinical data at that time were evaluated retrospectively. She had only mild proteinuria and hematuria but no photosensitivity or facial erythema. Anti-nuclear antibody was negative. Renal biopsy showed occasional lobulation and glomerular capillary double contour. The diagnosis of MPGN was definite. This might be a rare case of one person suffering from two types of glomerulonephritis, MPGN and MLN.

Adult↗

PubMed2006

An experimental study on the repair of full skin loss of nude mice with composite graft of epidermal stem cells.

This study is to constitute a composite skin substitute with epidermal stem cells (ESCs) and fibroblasts on collagen sponge. ESCs were selected by rapid attachment to collagen IV for 10 min. Collagen was extracted from rat's tail. The matrix lattice was fabricated by freeze-dryer and cross-linked with glutaraldehyde. Fibroblasts were inoculated on collagen sponge and cultured for 1 week prior to inoculation of ESCs. Having cultured for 2 weeks in submerged culture, the bioengineered tissue was raised to the air-liquid interface and cultured for 2 weeks. The artificial skin was then grafted onto full skin loss wounds of nude mice. Collagen sponge membrane lacking cell inoculation and an artificial skin with epidermal cells (ECs) and fibroblasts were used as controls. The wounds were observed daily. Tissue samples were harvested and examined by means of histology, immunohistochemistry and electron microscopy. The wounds in the test group healed at a significantly faster rate than controls, with good skin appearance and minimal scar formation. The control group showed delayed wound healing and intensive wound contraction as compared to the test group. Thus the skin substitute with ESCs seemed to be a good equivalent.

Animals↗

PubMed2006

The effect of D,L-beta-hydroxybutyric acid on cell death and proliferation in L929 cells.

As a prerequisite for tissue engineering applications, researchers must understand the effect on local cell types of the degradation products of biodegradable polymers. Polyhydroxybutyrate (PHB) has received special interest as an implant material, because it degrades to release a normal component of blood and tissue, D,L-beta-hydroxybutyrate (HB). We report that HB (0.02 g/l) promoted cell proliferation in cultured L929 cells plated at high cell density (1 x 10(5) cells/well) but not lower cell densities. While HB did not affect cell cycle progression, it significantly inhibited cell death. HB treatment prevented necrosis, reducing cell membrane permeability 4h following serum withdrawal from the medium, and for all subsequent time points. In summary, HB promotes proliferation of L929 cells in high-density cultures by preventing apoptotic and necrotic cell death. This property makes biodegradable polymers containing HB, such as PHBHHx, attractive candidates for tissue engineering applications, especially those requiring the regeneration of large numbers of cells.

3-Hydroxybutyric Acid↗

PubMed2006

In vivo studies of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) based polymers: biodegradation and tissue reactions.

The in vivo tissue reactions and biodegradations of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), poly(lactide) (PLA), poly(3-hydroxybutyrate) (PHB), blends of PHBHHx (X) and poly(ethylene glycol) (PEG) (E) with ratios of 1:1 (E1X1) and 1:5 (E1X5), respectively, were evaluated by subcutaneous implantation in rabbits. Results revealed that the degradation rate increased in the order of PHB < PHBHHx < PLA. During the implantation period, crystallinity of PHBHHx increased from 19% to 22% and then dropped to 14%. Gel permeation chromatography (GPC) displayed increasing polydispersity and typical bimodal distribution from 3 to 6 months. The above results suggested that rapid PHBHHx degradation occurred in amorphous region rather than in crystalline region. While the in vivo hydrolysis of PHB was found to start from a random chain scission both in amorphous and crystalline regions of the polymer matrix, as demonstrated by its hydrolysis process accompanied by a decrease in molecular weight with unimodal distribution and relatively narrow polydispersity. Compared to pure PHBHHx, PHBHHx-PEG blends showed accelerated weight loss of PHBHHx with weak molecular weight reduction. In general, PHBHHx elicited a very mild tissue response during implantation lasting 6 months compared with relative acute immunological reactions observed among PHB and PLA objects, respectively. Pronounced tissue responses were observed in the capsule surrounding E1X1 and E1X5 as characterized by the presence of lymphocytes, eosinophils and vascularization, which might be resulted from the continuous leaching of PEG.

3-Hydroxybutyric Acid↗

PubMed2006

Mechanism of substrate specificity in Bacillus subtilis ResA, a thioredoxin-like protein involved in cytochrome c maturation.

The covalent attachment of heme cofactors to the apo-polypeptides via thioether bonds is unique to the maturation of c-type cytochromes. A number of thiol-disulfide oxidoreductases prepare the apocytochrome for heme insertion in system I and II cytochrome c maturation. Although most thiol-disulfide oxidoreductases are nonspecific, the less common, specific thiol-disulfide oxidoreductases may be key to directing the usage of electrons. Here we demonstrate that unlike other thiol-disulfide oxidoreductases, the protein responsible for reducing oxidized apocytochrome c in Bacillus subtilis, ResA, is specific for cytochrome c550 and utilizes alternate conformations to recognize redox partners. We report solution NMR evidence that ResA undergoes a redox-dependent conformational change between oxidation states, as well as data showing that ResA utilizes a surface cavity present only in the reduced state to recognize a peptide derived from cytochrome c550. Finally, we confirm that ResA is a specific thiol-disulfide oxidoreductase by comparing its reactivity to our mimetic peptide with its reactivity to oxidized glutathione, a nonspecific substrate. This study biochemically demonstrates the specificity of this thiol-disulfide oxidoreductase and enables us to outline a structural mechanism of regulating the usage of electrons in a thiol-disulfide oxidoreductase system.

Bacillus subtilis↗

PubMed2006

Effect of 3-hydroxyhexanoate content in poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) on in vitro growth and differentiation of smooth muscle cells.

In this paper, comprehensive characteristics including cell attachment, cell proliferation status, cell cycle progression and phenotypic changes of smooth muscle cells from rabbit aorta (RaSMCs) were studied on poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) containing 0-20% HHx (mol%) in comparison with tissue culture plates (TCPs). Results demonstrated that RaSMCs adhered better on PHBHHx containing 12% HHx (12%HHx) although they proliferated better on 20%HHx-containing PHBHHx films (20%HHx). This was explained by the difference in cell cycle progression observed using flow cytometry, as it was found that only 20%HHx-containing polymer could maintain the normal cell cycle evolution as TCPs did after 3 d incubation. The highest expression level and typical spindle-like distribution of alpha-actin on 20%HHx-containing polymer were characterized as the contractile-like phenotype, suggesting that RaSMCs tended to differentiate rather than proliferate compared to the cells grown on 12%HHx polymer. Results obtained above suggested that 20%HHx was suitable for RaSMCs proliferation, leading to its change to contractile phenotype. This study extends the potential applications of PHBHHx in SMCs-related graft scaffold fabrication for tissue engineering.

3-Hydroxybutyric Acid↗

PubMed2006

An alternative strategy for high throughput generation and characterization of monoclonal antibodies against human plasma proteins using fractionated native proteins as immunogens.

Construction of a monoclonal antibody (mAb) bank containing a vast variety of antibodies against human tissue proteins is important for proteomic research. A novel strategy of subtractive immunization using fractionated native proteins was developed for high throughput generation of mAb against human plasma proteins. By this novel approach, the bottleneck of antigen preparation can be overcome by combining repeated immunization of animals with subtracted fractions of plasma or tissue proteins and identification of target antigen by immunoprecipitation/mass spectrum strategies. Plasma freshly collected from healthy adults was pooled and three fractions were prepared by size exclusion chromatography. Mice were immunized with the fractionated plasma proteins, and 205 strains of hybridomas secreting mAb were obtained after two-round subtractive immunizations and cell fusions. In the first round, 110 strains of hybridomas were established, in which 77 strains secreting mAb were identified against 10 human plasma high-abundant proteins. In the second round, plasma fraction I was absorbed with mAb against IgM, IgG, ceruloplasmin and haptoglobin. The absorbed fraction I was used as immunogen for the second round immunization and cell fusion. Ninety-five strains of hybridomas secreting mAb were obtained. Although the target antigens of mAb from 82 strains of hybridomas were identified as IgM, IgA, alpha2-macroglobulin and fibrinogen, about 85% antibodies obtained from this round were identified as new antibodies when compared with mAb obtained in the first round immunization with plasma fraction I. The results suggest that subtractive immunization with fractionated plasma proteins followed by identification of antigens with immunoprecipitation/mass spectrum may be an effective approach for rapid preparation of mAb against high-and medium-abundant plasma or tissue proteins.

Amino Acid Sequence↗

PubMed2006

Proteomics-based generation and characterization of monoclonal antibodies against human liver mitochondrial proteins.

Monoclonal antibodies (mAbs) have the potential to be a very powerful tool in proteomics research to determine protein expression, quantification, localization and modification, as well as protein-protein interactions, especially when combined with microarray technology. Thus, a large amount of well-characterized and highly qualified antibodies are needed in proteomics. Purified antigen, which is not always available, has proven to be one of the rate-limiting steps in mAb large-scale generation. Here we describe our strategies to establish a murine hybridoma cell bank for human liver mitochondria using unknown native proteins as the immunogens. The antibody-recognized mitochondrial proteins were identified by MS following immunoprecipitation (IP), and by screening of human liver cDNA expression library. We found that the established antibodies reacted specifically with a number of important enzymes in mitochondria. The subcellular localization of these antigens in mitochondria was further confirmed by immunohistocytochemistry. A panel of antibodies was also tested for their ability to capture and deplete the targeting proteins and complexes from the total mitochondrial proteins. We believe these well-characterized antibodies would be useful in various applications for Human Liver Proteome Project (HLPP) when the scale of this hybridoma cell bank is enlarged significantly in the near future.

Antibodies, Monoclonal↗

PubMed2006

On impact dynamics and contact events for biped robots via impact effects.

In this paper, impact dynamics of a five-link biped walking on level ground are studied, and the results are used to correlate the gait parameters with the contact event following impact. The conventional five-link biped kinematic model is improved such that, for the first time, the explicit solution for the external impulses is obtained in a detailed but compact form. Such a solution reveals that the direction of the swing tip velocity prior to impact is a key factor dictating the upcoming contact event and the slippage. The conventional conditions to warrant the types of impact are expanded to make them sufficient. The aforementioned results are used in the parametric analysis to predict the contact event after impact. Such a prediction is important for proper dynamic modeling, motion planning, and control of the upcoming supporting phase.

Gait↗

PubMed2006

Antioxidative flavanone glycosides from the branches and leaves of Viscum coloratum.

Two new flavanone glucosides, (2S)-homoeriodictyol 7,4'-di-O-beta-D-glucopyranoside (4) and (2R)-eriodictyol 7,4'-di-O-beta-D-glucopyranoside (5) were isolated from the branches and leaves of Viscum coloratum (KOMAR) NAKAI (Loranthaceae), along with three known flavanone glucosides: (2S)-homoeriodictyol 7-O-beta-D-glucopyranoside (1), (2S)-eriodictyol 7-O-beta-D-glucopyranoside (2), and (2S)-naringenin 7-O-beta-D-glucopyranoside (3). The structures of these compounds were elucidated using spectroscopic methods. The antioxidant activities of these isolated compounds were evaluated by colorimetric methods based on their scavenging effects on hydroxyl radicals and superoxide anion radicals, respectively. All the compounds showed potent albeit varied degrees of antioxidative activities and the structure-activity relationship is discussed.

Antioxidants↗

PubMed2006

Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term.

Mouse parthenogenetic embryos (PEs) are developmentally arrested until embryo day (E) 9.5 because of genomic imprinting. However, we have shown that embryos containing genomes from non-growing (ng) and fully grown (fg) oocytes, i.e. ng(wt)/fg(wt) PE (wt, wild type), developed to E13.5. Moreover, parthenogenetic development could be extended to term by further regulation of Igf2 and H19 expression using mice with deletion of the H19 transcription unit (H19Delta13) together with its differentially unit (DMR). To gain an insight into the extended development of the parthenotes to term, we have here investigated the expression levels of paternally imprinted genes in ng(H19Delta13)/fg(wt) PE throughout their development. In ng(H19Delta13)/fg(wt) Pes that died soon after recovery, the expression of Igf2 and H19 was restored to the appropriate levels except for low Igf2 expression in the liver after E15.5. Further, the paternally expressed Dlk1 and Dio3 were repressed, while the expression levels of the maternal Gtl2 and Mirg were twice those of the controls. However, the above-mentioned four genes showed almost normal expression in the surviving ng(H19Delta13)/fg(wt) PEs. The methylation analysis revealed that the intragenic DMR of the Dlk1-Gtl2 domain was hypermethylated in the ng(H19Delta13)/fg(wt) PEs that survived, but not in the PEs that died soon after recovery. The present study suggests that two sets of co-ordinately regulated but oppositely expressed genes, Igf2-H19 and Dlk1-Gtl2, act as a critical barrier to parthenogenetic development in order to render a paternal contribution obligatory for descendants in mammals.

Animals↗

PubMed2006

[Statistical properties of Markov chain in land use and landscape study].

Markov chain has been widely applied in the study of land use and landscape changes, but its statistical properties were less tested. Based on the land use change data monitored in Beijing, and with Pearson chi-squared goodness-of-fit test, this paper examined the time stability and time independence of Markov chain of land use change. The results indicated that the hypothesis of time stationary and Markov property is not tenable, which meant that the land use change in Beijing was an un-stationary and highly order Markov chain. Pearson chi-squared test was not as restricted a the likelihood ratio test, its transitional probabilities being allowed to be greater than zero, and thus, could be more useful in testing the assumption of homogeneity and independence.

China↗