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Biomedical subjects

Hui Liu

Publications and source records attributed to Hui Liu.

At least 55 records · Page 3Linked to original sources

C60 thin film growth on graphite: Coexistence of spherical and fractal-dendritic islands.

The initial growth stage of C(60) thin film on graphite substrate has been investigated by scanning tunneling microscopy in ultrahigh vacuum at room temperature. The C(60) layer grows in a quasi-layer-by-layer mode and forms round, monolayer high islands on the graphite surface. The islands are confined by terraces on the graphite surface and the mobility of C(60) fullerenes across steps is low in all layers. The second and all subsequent layers adopt a fractal-dendritic shape, which was confirmed by calculating the fractal dimension (D=1.74 prior to island coalescence) and is in agreement with a diffusion limited aggregation. The profound differences between the growth of C(60) layers on graphite (first layer) and on C(60) surfaces (second and higher layers) are caused by the restriction of the C(60) mobility on the highly corrugated fullerene surfaces. The orientation of the fractal islands follows the hexagonal symmetry of the densely packed (111) surface of the fullerene lattice, which introduces a bias in the direction of molecule movement. The differences in surface topography on the nanoscale determine the mode of film growth in this van der Waals bonded system.

Journal Article↗

Ubc9 interacts with SOX4 and represses its transcriptional activity.

SOX4 is a member of SOX transcriptional factor family that is crucial for many cellular processes. In this study, a yeast two-hybrid screening of human mammary cDNA library identified human ubiquitin-conjugating enzyme 9 (hUbc9) that interacted with SOX4. This interaction was confirmed by GST pull-down in vitro and co-immunoprecipitation assays in vivo. Deletion mapping demonstrated that HMG-box domain of SOX4 is required to mediate the interaction with Ubc9 in yeast. Furthermore, confocal microscopy showed that Ubc9 co-localized with SOX4 in the nucleus. Luciferase assays found that Ubc9 specifically repressed SOX4 transcriptional activity in 293T cells. We further demonstrated that Ubc9 could functionally repress the transcriptional activity of endogenous SOX4 induced by progesterone in T47D cells. The C93S mutant of Ubc9, which abrogates SUMO-1 conjugation activity, did not abolish the ability to repress SOX4 activity. It shows that Ubc9 interacts with SOX4 and represses its transcriptional activity independent of its SUMO-1-conjugating activity.

High Mobility Group Proteins↗

Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and then undergo a sol-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, gatifloxacin, based on the concept of ion-activated in situ gelation. Alginate (Kelton) was used as the gelling agent in combination with HPMC (Methocel E50Lv) which acted as a viscosity-enhancing agent. The rheological behaviors of all formulations were not affected by the incorporation of gatifloxacin. Both in vitro release studies and in vivo pre-corneal retention studies indicated that the alginate/HPMC solution retained the drug better than the alginate or HPMC E50Lv solutions alone. These results demonstrate that the alginate/HPMC mixture can be used as an in situ gelling vehicle to enhance ocular bioavailability and patient compliance.

Alginates↗

A new class of glucosidase inhibitor: analogues of the naturally occurring glucosidase inhibitor salacinol with different ring heteroatom substituents and acyclic chain extension.

Six chain-extended analogues of the naturally occurring glycosidase inhibitor salacinol, with ring-heteroatom variation, were synthesized for structure-activity studies with different glycosidase enzymes. The syntheses involved the reaction of PMB-protected D- and L- seleno-, thio-, and iminoarabinitol with a benzylidene- and isopropylidene-protected 1,3-cyclic sulfate, derived from commercially available D-sorbitol, in 1,1,1,3,3,3-hexafluoro-2-propanol containing potassium carbonate. Deprotection of the products afforded the novel selenonium, sulfonium, and iminium analogues of salacinol containing polyhydroxylated, monosulfated, extended acyclic chains of 6-carbons, differing in stereochemistry at the stereogenic centers and ring-heteroatom constitution. Four of these compounds inhibit recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with Ki values in the micromolar range, thus providing lead candidates for the treatment of Type 2 diabetes.

Acids, Acyclic↗

Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival.

Genetic variation in DNA repair may affect the clinical response to cytotoxic therapies. We investigated the effect of six single nucleotide polymorphisms of the RecQ1, RAD54L, XRCC2, and XRCC3 genes on overall survival of 378 patients with pancreatic adenocarcinoma who were treated at University of Texas M.D. Anderson Cancer Center during February 1999 to October 2004 and were followed up to October 2005. Genotypes were determined using the MassCode method. Survival was determined from pathologic diagnosis to death. Patients who were alive at the last follow-up evaluation were censored at that time. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare overall survival by genotypes. A significant effect on survival of all patients was observed for RecQ1 and RAD54L genes. The median survival time was 19.2, 14.7, and 13.2 months for the RecQ1 159 AA, AC, and CC genotypes, and 16.4, 13.3, and 10.3 months for RAD54L 157 CC, CT, and TT genotypes, respectively. A significantly reduced survival was associated with the variant alleles of XRCC2 R188H and XRCC3 A17893G in subgroup analysis. When the four genes were analyzed in combination, an increasing number of adverse alleles were associated with a significantly decreased survival. Subgroup analyses have shown that the genotype effect on survival was present among patients without metastatic disease or among patients who receive radiotherapy. These observations suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly affect the clinical outcome of patients with pancreatic cancer.

Adenosine Triphosphatases↗

[Effect of inhibitors of signal transducer and activator of transcription-1/3 on expression of tumor necrosis factor-alpha induced by high mobility group box-1 protein inflammatory response in rat peritoneal macrophages].

OBJECTIVE: To investigate the inflammatory signal transduction of high mobility group box-1 protein (HMGB1) induced inflammatory response in rat peritoneal macrophages. METHODS: Peritoneal macrophages obtained from male Wistar rats were seeded in 24-well (1 x 10(6) cells/well) tissue culture plates. The cells were incubated for 3 days before they were stimulated with HMGB1, and treated with Fludarabine [the specific inhibitor of signal transducer and activator of transcription 1 (STAT1)] or Rapamycin (the specific inhibitor of STAT3). The time-dependent and dose-dependent responses between HMGB1 stimulation and tumor necrosis factor-alpha (TNF-alpha) gene expression as well as release were analyzed respectively. Moreover, the effect of Fludarabine and Rapamycin on TNF-alpha mRNA expression and protein release were also observed. RESULTS: (1) After HMGB1 challenge, TNF-alpha mRNA expressions were up-regulated markedly, peaked at 24 hours, and decreased at 36 hours. When HMGB1 was used at a concentration of 10 microg/ml, TNF-alpha mRNA expression increased most markedly. (2) HMGB1 could induce TNF-alpha release in rat peritoneal macrophages, with peaking at 4 hours and decreasing at 8 hours later. When the concentration of HMGB1 stimulation increased from 5 microg/ml to 25 microg/ml, TNF-alpha release was persistently enhanced. (3) It was also showed that TNF-alpha mRNA expression was significantly inhibited by treatment of either Fludarabine (100 micromol/L) or Rapamycin (25 ng/ml), while TNF-alpha release was not markedly suppressed. CONCLUSIONS: STAT1 and STAT3 might be involved in the regulation of TNF-alpha gene expression, but not in TNF-alpha early release (< 24 hours) induced by HMGB1 stimulation in rat peritoneal macrophages.

Animals↗

Threshold estimation in children using auditory steady-state responses to multiple simultaneous stimuli.

OBJECTIVE: It was the aim of this study to explore the use of auditory steady-state response (ASSR) to multiple simultaneous stimuli for threshold estimation in young children. METHOD: The subjects consisted of 40 children, aged from 6 months to 5 years, with variant degrees of sensorineural hearing loss. Simultaneous tonepips (0.5, 1, 2 and 4 kHz) with an amplitude modulated at different rates from 77 to 103 Hz were presented to both ears by insert phones. All children were tested with ASSR and age-appropriate behavioral tests. RESULTS: We found that (1) ASSR thresholds were usually higher than behavioral thresholds with a difference of 8-15 dB, (2) the behavioral thresholds were significantly correlated with ASSR thresholds (p = 0.000), and (3) there was a great difference between ASSR thresholds and behavioral thresholds found in a child with auditory neuropathy. CONCLUSION: Being objective, frequency specific and well correlated with behavioral thresholds, ASSR to multiple simultaneous stimuli was proven to be a good tool to predict behavioral hearing thresholds.

Acoustic Stimulation↗

Proteomics-based identification of autoantibodies in the sera of healthy Chinese individuals from Beijing.

The identification of panels of tumor antigens that elicit an antibody response may have utility in cancer screening, diagnosis and in establishing prognosis. However, autoantibodies normally exist in sera of healthy individuals and are enormously diversified. To explore the reservoir of autoantibody in healthy population, we performed a proteomics investigation of autoantibody profiles in the sera of 36 healthy Chinese individuals from Beijing, which may provide valuable reference information to the identification of disease-specific autoantibodies. The results showed that autoantibody profiles varied individually, but some autoantibodies were identified at a high frequency in the healthy population. The autoantibodies against alpha-enolase and those against heterogeneous nuclear ribonucleoprotein L were positive in more than 50% of the sera samples. The autoantibodies identified in more than 20% of samples included those against annexin II, F-actin capping protein beta subunit and calreticulin. Some of these autoantibodies have been previously reported to be involved in autoimmune conditions and cancers. Autoantibodies in the healthy population are important as a foundation from which disease-specific autoantibodies can be defined. Thus our report on autoantibodies in healthy individuals may be useful as a reference for defining new autoantibody biomarkers.

Adult↗

Different effects of capsaicin on I(A) and I(K) in pain-conduct neurons of rats.

The different effects of capsaicin on I(A) and I(K) currents in pain-conduct neurons of trigeminal ganglia (TG) were investigated. In cultured TG neurons of rats, whole-cell patch clamp techniques were used to record the I(A) and I(K) before and after capsaicin perfused. Results revealed that 1 micromol/L capsaicin could inhibit the amplitude of I(A) by 48.2% (n = 10, P < 0.05), but had no inhibitory effect on I(K) (n = 7, P > 0.05). Ten micromol/L capsaicin could significantly inhibit the amplitude of I(A) by 93.2% (n = 8, P < 0.01), but only slightly inhibit the amplitude of I(K) by 13.2% (n = 7, P < 0.05). Neither 1 micromol/L nor 10 micromol/L capsaicin had effects on the active curve of I(A) and I(K). It was concluded that capsaicin could selectively inhibit the I(A) current, and this effect might involve in the analgesic mechanisms of capsaicin.

Animals↗

[Large recombinant protein displayed on filamentous phage surface and its interaction with small molecule].

Recombinant proteins were expressed as fusions with the phagemid system of pHEN-KM13 and the characteristics and activities of the fusion proteins displayed on the surface of filamentous phagintain the were studiedon abilty. The altered titer of rescued phages from the phagemid system after trypsin treatment indicated the relative quantity of the phages displaying fusion proteins. The rescue phages displayed foreign proteins could keep the bacterial infection ability, while the bald phage without foreign protein displayed on its surface was sensitive to trypsin treatment and lost the bacterial infection ability. To determine the upper limit for filamentous phage display, four recombinant proteins, glutathione-S-transferase and glutathione-S-transferase fused with three various size peptide linkers, were fused to N terminus of capsid protein gp3 and rescued by helper phage KM13. The rescued phages which displayed fused protein with the size of 40kD or less maintain the infection ability. To assay the activity of the phage displayed protein, the known small molecule probe was used in the interaction study with protein incorporated on phage surface. Results showed that the glutathione-S-transferase on phage surface still bound to glutathione specifically. It indicated that the glutathione-S-transferase displayed on phage surface was correctly folded and functionally active. The results demonstrated that it was feasible to use small molecule probes to interact with the protein displayed on phage surface. In turn, the method described here also demonstrated that phage display system could be utilized to investigate the interactions between protein and small molecules.

Glutathione↗

A convenient cell fusion assay for the study of SARS-CoV entry and inhibition.

SARS-CoV spike (S) protein-mediated cell fusion is important for the viral entry mechanism and identification of SARS-CoV entry inhibitors. In order to avoid the high risks involved in handling SARS-CoV and to facilitate the study of viral fusion mechanism, we established the cell lines: SR-COS7 cells that stably express both SARS-CoV S protein and red fluorescence protein, R-COS7 cells that stably express red fluorescence protein, and AG-COS7 cells that stably express both ACE2 and green fluorescence protein, respectively. When SR-COS7 cells or R-COS7 cells were cocultured with AG-COS7 cells, syncytia with yellow fluorescence were conveniently observed after 12 h in SR-COS7 cells plus AG-COS7 cells, but not in R-COS7 cells plus AG-COS7 cells. The cell-to-cell fusion efficiency was simply determined for quantitative analysis based on the number of syncytium detected by flow cytometry. Such new cell-to-cell fusion model was further assessed by the potent HR2 peptide inhibitor, which led to the obvious decrease of the cell-to-cell fusion efficiency. The successful fusion and inhibition of cell-based binding assay shows that it can be well used for the study of SARS-CoV entry and inhibition.

Angiotensin-Converting Enzyme 2↗

Men who have sex with men and human immunodeficiency virus/sexually transmitted disease control in China.

OBJECTIVES: To address the role of men who have sex with men (MSM) in the human immunodeficiency virus (HIV)/sexually transmitted disease (STD) epidemic in China. GOAL: To explore the prevalence of risky sexual behaviors and the existing prevention efforts among men who have sex with men (MSM) in China. STUDY DESIGN: Review of behavioral and STD/HIV prevention studies addressing MSM in China. RESULTS: Sexual risk behaviors including unprotected group sex, anal sex, casual sex, and commercial sex were prevalent among Chinese MSM. Many Chinese MSM also engaged in unprotected sex with both men and women. Most MSM either did not perceive that they were at risk of HIV/AIDS or underestimated their risk of infection. Surveillance and intervention research among these men are still in the preliminary stages. CONCLUSIONS: Chinese MSM are at risk for HIV/STD infection and potential transmission of HIV to the general population. In addition to sexual risk reduction among MSM, reduction of homosexuality- related stigma should be part of effective intervention efforts. Volunteers from the MSM community and health care workers in primary health care system may serve as valuable resources for HIV/STD prevention and control among MSM.

China↗

The Erwinia chrysanthemi 3937 PhoQ sensor kinase regulates several virulence determinants.

The PhoPQ two-component system regulates virulence factors in Erwinia chrysanthemi, a pectinolytic enterobacterium that causes soft rot in several plant species. We characterized the effect of a mutation in phoQ, the gene encoding the sensor kinase PhoQ of the PhoPQ two-component regulatory system, on the global transcriptional profile of E. chrysanthemi using cDNA microarrays and further confirmed our results by quantitative reverse transcription-PCR analysis. Our results indicate that a mutation in phoQ affects transcription of at least 40 genes, even in the absence of inducing conditions. Enhanced expression of several genes involved in iron metabolism was observed in the mutant, including that of the acs operon that is involved in achromobactin biosynthesis and transport. This siderophore is required for full virulence of E. chrysanthemi, and its expression is governed by the global repressor protein Fur. Changes in gene expression were also observed for membrane transporters, stress-related genes, toxins, and transcriptional regulators. Our results indicate that the PhoPQ system governs the expression of several additional virulence factors and may also be involved in interactions with other regulatory systems.

Bacterial Proteins↗

You make me sick: marital quality and health over the life course.

We work from a life course perspective and identify several reasons to expect age and gender differences in the link between marital quality and health. We present growth curve evidence from a national longitudinal survey to show that marital strain accelerates the typical decline in self-rated health that occurs over time and that this adverse effect is greater at older ages. These findings fit with recent theoretical work on cumulative adversity in that marital strain seems to have a cumulative effect on health over time-an effect that produces increasing vulnerability to marital strain with age. Contrary to expectations, marital quality seems to affect the health of men and women in similar ways across the life course.

Data Collection↗

SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.

Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid-binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid-dependent in vitro agglutination of erythrocytes (i.e., sialic acid-dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid-dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcalpha2-3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.

Adhesins, Bacterial↗

Impact of diabetes mellitus on treatment outcomes in patients with nasopharyngeal cancer.

BACKGROUND AND PURPOSE: To determine the influence of diabetes mellitus on stages and long-term outcomes among patients with nasopharyngeal cancer. MATERIAL AND METHODS: The study summarized 37 patients who were diagnosed as having diabetes mellitus and nasopharyngeal cancer and treated by radiotherapy between January 1999 and December 1999. With a median follow-up of 34.6 mo, we analyzed differences in RFS, MFS, DFS, and OS between the diabetes and the non-diabetes group. RESULTS: 37 patients were involved in our study. According to the Chinese Fuzhou staging system for NPC, which was modified in 1992, 2 patients belong to stage I, 9 stage II, 17 stage III, and 6 stage IV. The 4-yr RFS of diabetes group and non-diabetes group was 52.1% vs 68.2%, the 4-yr MFS was 73.0% vs 72.0%, the 4-yr DFS was 35.1% vs 65.1%, and the OS was 67.6% vs 75.7%. The Wilcoxon (Gehan) test showed there was no significant difference between the two groups of RFS, MFS, and OS, while the diabetes group had a worse DFS than non-diabetes group (Wilcoxon p = 0.0047). CONCLUSIONS: Patients with diabetes had a worse DFS than non-diabetes, but statistic tests did not show significant differences in RFS, MFS, and OS; further studies should be continue to find out the results in the future.

Adult↗

[Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in adenomyosis].

OBJECTIVE: To investigate the expressions of matrix metalloproteinase -2, -3 (MMP-2,-3) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in internal uterine endometriosis tissue and endometrium from women with and without endometriosis throughout the menstrual cycle. METHODS: Immunohistochemical staining of tissues was performed to study the expressions and locations of MMP-2, MMP-3, TIMP-2 between women with and without endometriosis. The real-time PCR technique was applied to detected the mRNA expressions of MMP-2, MMP-3 and TIMP-2. RESULTS: We found that ectopic endometrium from patients with endometriosis expressed higher levels of MMP-2 and MMP-3 and lower levers of TIMP-2 than normal controls did (P < 0.05). MMP-2 and MMP-3 were detected strongly in both stromal and epithelial cells of ectopic endometrium from patients with endometriosis, when mostly detected in the epithelial cells in the control group. All eutopic and ectopic endometrium samples from women with and without endometriosis throughout the menstrual cycle showed similar expressions of MMP-2, MMP-3 and TIMP-2. Quantitative expressions of MMP-2 mRNA, MMP-3 mRNA and TIMP-2 mRNA were significantly lower in eutopic endometrium from controls compared with ectopic endometrium from patients with endometriosis (P < 0.05). Eutopic endometrium from controls in the proliferative phase showed significantly increased expressions of MMP-2 mRNA compared with that in the secretory phase (P < 0.05). CONCLUSION: The results suggest that ectopic endometrium with adenomyosis has more invasiveness and is prone to peritoneal implantation maybe to involved in the high expressions of MMP-2 and MMP-3 and the less expressions of TIMP-2 than endometrium from women without adenomyosis does.

Adult↗

[Isolation of a novel peptide that binds to BLyS from a 12-mer phage display peptide library].

A 12-mer phage display peptide library was screened for specific binders against B lymphocyte stimulator (BLyS). After 3 rounds of panning, positive phage clones were enriched. ELISAs were used to identify positive phages, and the DNA encoding the positive peptide (RHKIQLRQNIIT) was cloned and expressed as a GST fusion protein in E. coli. After purification, the identity of the fusion protein was confirmed through its specific binding to BLyS by ELISA. We have obtained a peptide that can bind to BLyS and probably act as an antagonistic peptide against the natural BLyS receptor.

B-Cell Activating Factor↗