Biomedical subjects

Yi Zhang

Publications and source records attributed to Yi Zhang.

At least 73 records · Page 4Linked to original sources

PubMed2006

Down-regulated expression of complement factor I: a potential suppressive protein for gastric cancer identified by serum proteome analysis.

BACKGROUND: Screening tests are needed for gastric cancer. In order to find serologic biomarkers for gastric cancer screening, we used proteomics to search for protein biomarkers that may be detected in serum of gastric cancer patients. METHODS: Four groups of serum samples (from 20 gastric cancer patients) included pTNM stages I to IV were compared with two control groups of serum samples. The serum samples were first chromatographed using an immunoaffinity column to selectively remove albumin and IgG. Then serum proteins separated by 2-DE and identified by MALDI-TOF/TOF-MS. RESULTS: There were 3 proteins including complement C4-B precursor, complement factor I (CFI) precursor and haptoglobin precursor were found significantly different between the healthy and gastric cancer patients. Further validation study by Western blot showed that the detection of CFI precursor was under-expressed in gastric cancer sera compared to normal sera (p<0.05), in addition to a declining expression with the advanced pTNM stage from stage I to IV of gastric cancer patients. Area under the receiver operating characteristic (ROC) curve was 0.78 for the expression of CFI precursor (p<0.01). CONCLUSIONS: 2-DE-based serum proteome analysis may be useful in the screening of serum biomarkers for gastric cancer. CFI precursor could aid in the diagnosis and indicate the advancement of gastric cancer.

Adult↗

PubMed2006

Suppressor of cytokine signaling-3 suppresses the ability of activated signal transducer and activator of transcription-3 to stimulate neurite growth in rat primary sensory neurons.

The actions of the neuropoietic cytokines are mediated by the gp130 receptor, which activates several signaling molecules including the transcription factor STAT3 (signal transducer and activator of transcription), which, in turn, is subject to feedback inhibition by SOCS3 (suppressor of cytokine signaling). Activation of the gp130 receptor has been implicated in axonal growth particularly during regeneration, but the specific contribution of STAT3 is the subject of conflicting reports. Measurements of SOCS3 mRNA in rat dorsal root ganglia showed a significant induction in this inhibitory molecule after peripheral nerve injury. The functions of STAT3 and SOCS3 in adult rat primary sensory neurons were investigated in vitro through transduction of lentiviruses yielding a conditionally activated STAT3, native SOCS3, or a mutant SOCS3 with dominant-negative actions. The SOCS3 construct was effective in inhibiting tyrosine phosphorylation of STAT3 in a neuroblastoma cell line and in blocking nuclear accumulation of endogenous STAT3 or of the conditionally activated STAT3 chimera in primary sensory neurons. In such neurons, transduction and activation of STAT3 enhanced neurite growth, transduction with SOCS3 reduced neurite outgrowth, and transduction with mutant SOCS3 enhanced neurite growth, at least under basal conditions. In conclusion, STAT3 signaling is beneficial to axonal growth through activating transcription of unidentified genes, and SOCS3 is detrimental to axonal growth through inhibition of STAT3 and/or other transcription factors.

Active Transport, Cell Nucleus↗

PubMed2006

Electrochemically controlled formation and growth of hydrogen nanobubbles.

Electrogenerated microscale bubbles that are confined at the electrode surface have already been extensively studied because of their significant influence on electrochemistry. In contrast, as far as we know, whether nanoscale bubbles exist on the electrode surface has not been experimentally confirmed yet. Here, we report the observation of electrochemically controlled formation and growth of hydrogen nanobubbles on bare highly oriented pyrolytic graphite (HOPG) surface via in-situ tapping mode atomic force microscopy (TMAFM). By using TMAFM imaging, we observed that electrochemically generated hydrogen gas led to the formation of nanobubbles at the HOPG surface. We then employed a combination of techniques, including phase imaging, ex-situ degassing, and tip perturbation, to confirm the gas origin of such observed nanobubbles. We further demonstrated that the formation and growth of nanobubbles could be well controlled by tuning either the applied voltage or the reaction time. Remarkably, we could also monitor the evolution process of nanobubbles, that is, formation, growth, coalescence, as well as the eventual release of merged microbubbles from the HOPG surface.

Electrochemistry↗

PubMed2006

Thermodynamic and kinetic aspects of metal binding to the histidine-rich protein, Hpn.

The histidine-rich protein, Hpn, binds to essential metals Ni2+, Cu2+, Zn2+ and a therapeutic metal Bi3+ with the in vitro affinities in the order of Cu2+ > Ni2+ > Bi3+ > Zn2+. In contrast, the in vivo (in E. coli) protection by the protein is in the order of Ni2+ > Bi3+ > Cu2+ approximately Zn2+. The release of Ni2+ from the protein follows a two-step process consisting of a rapidly established equilibrium and subsequently a rate-determining step (dissociation of Hpn-Ni...EDTA to Ni-EDTA). Our work suggests the nickel storage and homeostasis in H. pylori as the primary role of Hpn.

Amino Acid Sequence↗

PubMed2006

Crystal structure of human histone lysine-specific demethylase 1 (LSD1).

Lysine-specific demethylase 1 (LSD1) was recently identified as the first histone demethylase that specifically demethylates monomethylated and dimethylated histone H3 at K4. It is a component of the CoREST and other corepressor complexes and plays an important role in silencing neuronal-specific genes in nonneuronal cells, but the molecular mechanisms of its action remain unclear. The 2.8-A-resolution crystal structure of the human LSD1 reveals that LSD1 defines a new subfamily of FAD-dependent oxidases. The active center of LSD1 is characterized by a remarkable 1,245-A3 substrate-binding cavity with a highly negative electrostatic potential. Although the protein core of LSD1 resembles other flavoenzymes, its enzymatic activity and functions require two additional structural modules: an N-terminal SWIRM domain important for protein stability and a large insertion in the catalytic domain indispensable both for the demethylase activity and the interaction with CoREST. These results provide a framework for further probing the catalytic mechanism and the functional roles of LSD1.

Catalytic Domain↗

PubMed2006

The Chk1/Cdc25A pathway as activators of the cell cycle in neuronal death induced by camptothecin.

Cell cycle regulators appear to play a paradoxical role in neuronal death. We have shown previously that cyclin-dependent kinases (CDKs), along with their downstream effectors, Rb (retinoblastoma) and E2F/DP1 (E2 promoter binding factor/deleted in polyposis 1), regulate neuronal death evoked by the DNA damaging agent camptothecin. However, the mechanism by which CDKs are activated in this model is unclear. The cell division cycle 25A (Cdc25A) phosphatase is a critical regulator of cell cycle CDKs in proliferating cells. In cortical neurons, we presently show that expression of Cdc25A promotes death even in the absence of DNA damage. Importantly, Cdc25A activity is rapidly increased during DNA damage treatment. Inhibition of Cdc25A blocks death and reduces cyclin D1-associated kinase activity and Rb phosphorylation. This indicates that endogenous Cdc25A activity is important for regulation of cell cycle-mediated neuronal death. We also examined how Cdc25A activity is regulated after DNA damage. Cultured embryonic cortical neurons have a significant basal activity of checkpoint kinase 1 (Chk1), a kinase that regulates cell cycle arrest. During camptothecin treatment of neurons, this activity is rapidly downregulated with a concomitant increase in Cdc25A activity. Importantly, expression of wild-type Chk1, but not kinase-dead Chk1, inhibits the camptothecin-induced increase in Cdc25A activity. In addition, Chk1 expression also promotes survival in the presence of the DNA-damaging agent. Together, our data suggest that a Chk1/Cdc25A activity participates in activation of a cell cycle pathway-mediated death signal in neurons. These data also define how a proliferative signal may be abnormally activated in a postmitotic environment.

Animals↗

PubMed2006

Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L.

Chromosomal translocation is a common cause of leukaemia and the most common chromosome translocations found in leukaemia patients involve the mixed lineage leukaemia (MLL) gene. AF10 is one of more than 30 MLL fusion partners in leukaemia. We have recently demonstrated that the H3K79 methyltransferase hDOT1L contributes to MLL-AF10-mediated leukaemogenesis through its interaction with AF10 (ref. 5). In addition to MLL, AF10 has also been reported to fuse to CALM (clathrin-assembly protein-like lymphoid-myeloid) in patients with T-cell acute lymphoblastic leukaemia (T-ALL) and acute myeloid leukaemia (AML). Here, we analysed the molecular mechanism of leukaemogenesis by CALM-AF10. We demonstrate that CALM-AF10 fusion is both necessary and sufficient for leukaemic transformation. Additionally, we provide evidence that hDOT1L has an important role in the transformation process. hDOT1L contributes to CALM-AF10-mediated leukaemic transformation by preventing nuclear export of CALM-AF10 and by upregulating the Hoxa5 gene through H3K79 methylation. Thus, our study establishes CALM-AF10 fusion as a cause of leukaemia and reveals that mistargeting of hDOT1L and upregulation of Hoxa5 through H3K79 methylation is the underlying mechanism behind leukaemia caused by CALM-AF10 fusion.

Animals↗

PubMed2006

Algorithmic and complexity results for decompositions of biological networks into monotone subsystems.

A useful approach to the mathematical analysis of large-scale biological networks is based upon their decompositions into monotone dynamical systems. This paper deals with two computational problems associated to finding decompositions which are optimal in an appropriate sense. In graph-theoretic language, the problems can be recast in terms of maximal sign-consistent subgraphs. The theoretical results include polynomial-time approximation algorithms as well as constant-ratio inapproximability results. One of the algorithms, which has a worst-case guarantee of 87.9% from optimality, is based on the semidefinite programming relaxation approach of Goemans-Williamson [Goemans, M., Williamson, D., 1995. Improved approximation algorithms for maximum cut and satisfiability problems using semidefinite programming. J. ACM 42 (6), 1115-1145]. The algorithm was implemented and tested on a Drosophila segmentation network and an Epidermal Growth Factor Receptor pathway model, and it was found to perform close to optimally.

Algorithms↗

PubMed2006

Effect of synthesis parameters on the chromium content and catalytic activities of mesoporous Cr-MSU-x prepared under acidic conditions.

A series of chromium-incorporated MSU-x mesoporous molecular sieves were synthesized under different templates, initial Si/Cr molar ratios, aging times, and temperatures in acid solution. The synthesis was performed by using sodium silicate, chromium nitrate, and nonionic poly(ethylene oxide) surfactant as the source of silicone, metal, and the template, respectively. The Cr-MSU-x products were analyzed by inductively couple plasma-optical emission spectrometry to determine the actual Cr content and were characterized by X-ray diffraction, N(2) adsorption-desorption, scanning electron microscopy, high-resolution transmission electron microscopy, diffuse reflectance UV-visible, X-ray adsorption near-edge spectroscopy, and temperature-programmed reduction techniques. The Cr species were mostly formed as Cr(VI) in tetrahedral coordination. Two kinds of Cr(VI) species with different reduction abilities were distinguished. The catalytic activities of Cr-MSU-x in the dehydrogenation of ethane to ethylene with CO(2) were investigated at the same time. The synthesis parameters explored strongly influence the chromium content in Cr-MSU-x and, subsequently, the catalytic activities. The Cr-MSU-x synthesized with Si/Cr = 20, aging at 25 degrees C for 22 h, and templating by fatty alcohol polyoxyethylene ether gave the best activities, resulting in 58.0% ethane conversion and 92.1% ethylene selectivity. The Cr species in Cr-MSU-x are more efficient in activating and converting ethane molecules than are conventional catalysts.

Journal Article↗

PubMed2006

Distribution and expression of tissue inhibitors of metalloproteinase in dorsal root entry zone and dorsal column after dorsal root injury.

To understand whether tissue inhibitors of metalloproteinase (TIMPs) contribute to the failure of regenerating sensory axons to enter the spinal cord, we used in situ hybridization and immunocytochemistry to examine the expression of TIMP1, TIMP2, and TIMP3 in the dorsal root, dorsal root entry zone (DREZ), and dorsal column after dorsal root injury in adult rats. We found that the three TIMPs and their mRNAs were up-regulated in a time-, region-, and cell-type-specific manner. Strong up-regulation of all three TIMPs was seen in the injured dorsal roots. TIMP2 was also significantly up-regulated in the DREZ and degenerating dorsal column, where TIMP1 and TIMP3 showed only moderate up-regulation. Most cells up-regulating the TIMPs in the DREZ and degenerating dorsal column were reactive astrocytes, but TIMP2 was also up-regulated by microglia/macrophages, especially at long postoperative survival times. These results suggest that TIMPs may be involved in controlling tissue remodelling following dorsal root injury and that manipulation of the expression of TIMPs may provide a means of promoting axonal regeneration into and within the injured spinal cord.

Animals↗

PubMed2006

Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung.

Non-small-cell lung cancers (NSCLC) compose 80% of all lung carcinomas with squamous cell carcinomas (SCC) and adenocarcinoma representing the majority of these tumors. Although patients with early-stage NSCLC typically have a better outcome, 35% to 50% will relapse within 5 years after surgical treatment. We have profiled primary squamous cell lung carcinomas from 129 patients using Affymetrix U133A gene chips. Unsupervised analysis revealed two clusters of SCC that had no correlation with tumor stage but had significantly different overall patient survival (P = 0.036). The high-risk cluster was most significantly associated with down-regulation of epidermal development genes. Cox proportional hazard models identified an optimal set of 50 prognostic mRNA transcripts using a 5-fold cross-validation procedure. Quantitative reverse transcription-PCR and immunohistochemistry using tissue microarrays were used to validate individual gene candidates. This signature was tested in an independent set of 36 SCC samples and achieved 84% specificity and 41% sensitivity with an overall predictive accuracy of 68%. Kaplan-Meier analysis showed clear stratification of high-risk and low-risk patients [log-rank P = 0.04; hazard ratio (HR), 2.66; 95% confidence interval (95% CI), 1.01-7.05]. Finally, we combined the SCC classifier with our previously identified adenocarcinoma prognostic signature and showed that the combined classifier had a predictive accuracy of 71% in 72 NSCLC samples also showing significant differences in overall survival (log-rank P = 0.0002; HR, 3.54; 95% CI, 1.74-7.19). This prognostic signature could be used to identify patients with early-stage high-risk NSCLC who might benefit from adjuvant therapy following surgery.

Adenocarcinoma↗

PubMed2006

Effects of modification of the active site tyrosine of human DNA topoisomerase I.

The human topoisomerase I-mediated DNA relaxation reaction was studied following modification of the enzyme at the active site tyrosine (position 723). A series of unnatural tyrosine analogues was incorporated into the active site of human topoisomerase I by utilizing misacylated suppressor tRNAs in an in vitro protein synthesizing system. The relaxation activities of the modified human topoisomerase I analogues having varied steric, electronic, and stereochemical features were all greatly diminished relative to that of the wild type. It was found that modifications involving replacement of the nucleophilic tyrosine OH group with NH2, SH, or I groups eliminated DNA relaxation activity, as did changing the orientation of the nucleophilic tyrosine OH group. Only tyrosine analogues having the phenolic OH group in the normal position with respect to the protein backbone were active; the relative activities could be rationalized in chemical terms on the basis of the H-bonding and the electronic effects of the substituents attached to the meta position of the aromatic ring. In addition, the poisoning of one of the modified human topoisomerase I analogues, as part of covalent binary complexes with DNA, by CPT and 20-thio CPT was evaluated.

Binding Sites↗

PubMed2006

Chronic restraint stress modulates expression of genes in murine spleen.

Psychological and physical stress can alter the immune system in both humans and animals. We have reported that mice subjected to chronic 12-h daily physical restraint for 2 days showed dramatic apoptosis in splenocytes. To identify genes that contribute to the splenocyte apoptosis, we compare gene expression in the spleens of restrained and unstressed mice using oligo microarrays consisting of 226 genes. We report here that mice subjected to chronic 12-h daily physical restraint for 2 days exhibited significantly altered expression of 50 of 226 genes. These genes included pro-apoptotic genes. We selected 5 genes of interest and confirmed the microarray results by real-time PCR. In this study, we identify a potentially important component of pro-apoptotic activity in restraint stress and suggest a possible target for anti-apoptotic therapy to protect splenocytes against stress-induced apoptosis.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice.

AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo. METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model was established successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method. RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%, 58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P < 0.05), whereas there were no significant differences (P > 0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group. CONCLUSION: rhGH does not accelerate the proli-feration of human gastric cancer cell in vivo.

Animals↗

PubMed2006

Over-expression and characterization of the recombinant small heat shock protein from Pyrococcus furiosus.

The gene encoding a small heat shock protein (sHSP) from Pyrococcus furiosus was redesigned and chemically synthesized by using bacteria-preferred codons. The gene product was over-expressed in Escherichia coli BL21(DE)(3) and purified to homogeneity. In the presence of this protein, the activities of Taq DNA polymerase, DNA restriction endonuclease HindIII and lysozyme were protected at elevated temperature, and also, thermal aggregation of lysozyme was prevented by this purified recombinant sHSP.

Enzyme Activation↗

PubMed2006

Targeted gene disruption of methionine aminopeptidase 2 results in an embryonic gastrulation defect and endothelial cell growth arrest.

The antiangiogenic agent fumagillin (Fg) and its analog TNP-470 bind to intracellular metalloprotease methionine aminopeptidase-2 (MetAP-2) and inhibit endothelial cell growth in a p53-dependent manner. To confirm the role of MetAP-2 in endothelial cell proliferation and to validate it as a physiological target for the Fg class of antiangiogenic agents, we have generated a conditional MetAP-2 knockout mouse. Ubiquitous deletion of the MetAP-2 gene (MAP2) resulted in an early gastrulation defect, which is bypassed in double MetAP-2/p53 knockout embryos. Targeted deletion of MAP2 specifically in the hemangioblast lineage resulted in abnormal vascular development, and these embryos die at the midsomite stage. In addition, knockdown of MetAP-2 using small interfering RNA or homologous recombination specifically suppresses the proliferation of cultured endothelial cells. Together, these results demonstrate an essential role for MetAP-2 in angiogenesis and indicate that MetAP-2 is responsible for the endothelial cell growth arrest induced by Fg and its derivatives.

Aminopeptidases↗

PubMed2006

The role of leptin in leptin resistance and obesity.

Although the presence of hyperleptinemia with leptin resistance and obesity has long been recognized, a causal role of elevated leptin in these biological states remains unclear. This article summarizes some recent work from our laboratory supporting the concept that leptin, in and of itself, promotes leptin resistance and such resistance compounds the metabolic impact of diet-induced obesity. Results from multiple studies demonstrate that (1) chronically elevated central leptin decreases hypothalamic leptin receptor expression and protein levels and impairs leptin signaling; (2) leptin resistance and obesity are associated with reduced leptin receptors and diminished maximal leptin signaling capacity; and (3) leptin resistance confers increased susceptibility to diet-induced obesity. In essence, the augmented leptin accompanying obesity contributes to leptin resistance, and this leptin resistance promotes further obesity, leading to a vicious cycle of escalating metabolic devastation.

Age Factors↗

PubMed2006

Coexistence of liquid and solid phases of Bmim-PF6 ionic liquid on mica surfaces at room temperature.

In this communication, we report the coexistence of liquid and solid phases of room temperature ionic liquid (IL) [Bmim][PF6] on mica surfaces, observed by tapping mode atomic force microscopy (AFM) in air. Multilayers as well as drop-on-the-layer structures of the ionic liquid are revealed. The solid layers were very stable, and their orientations were affected by the mica lattice, indicating that the ionic liquid undergoes a template-induced ordering process. These results are helpful for advancing the understanding of interfacial structures of ILs on solid surfaces, the analogous structural patterns in both of its solid and liquid phases, and its heterogeneity.

Journal Article↗