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Liang Xu

Publications and source records attributed to Liang Xu.

At least 73 records · Page 4Linked to original sources
PubMed2004

Structure-based design of potent, conformationally constrained Smac mimetics.

A successful structure-based design and synthesis of a class of highly potent conformationally constrained Smac mimetics is described. The most potent compound has a Ki value of 25 nM binding to the XIAP BIR3 protein and is 23 times more potent than natural Smac peptides. These potent Smac mimetics can serve as powerful chemical and pharmacological tools to further elucidate the role of Smac and its cellular binding partners in apoptosis regulation and may be developed as a new class of anti-cancer drugs.

Apoptosis Regulatory Proteins↗
PubMed2004

Rapid biogenesis and sensitization of secretory lysosomes in NK cells mediated by target-cell recognition.

Natural killer (NK) cells play important roles in defense against tumor, viral infection, and cell-mediated xenograft rejection through secretion of secretory lysosomes. In this study, we used high time-resolution membrane capacitance measurement and fluorescence-imaging techniques to study the biogenesis and exocytosis of secretory lysosomes in a human NK cell line. We demonstrated a high-affinity Ca(2+)-dependent exocytosis of secretory lysosomes, which is sensitized further after target-cell stimulation. Our data also suggest an unusual rapid and dramatic de novo formation of secretory lysosomes after target-cell recognition. The rapid biogenesis of secretory lysosomes was blocked by specific protein kinase C inhibitor but not by brefeldin A. We propose that target-cell recognition triggers rapid biogenesis and sensitization of secretory lysosomes in NK cells through activation of PKC.

Calcium↗
PubMed2004

[The expression of c-fos and transmitter calcitonin gene-related peptide in the chronic compressive injury of the nerve root].

OBJECTIVES: To investigate the significance of c-fos oncogene morphogenetic protein's locational expression, and the correlativity between nerve transmitters calcitonin gene-related peptide (CGRP) expression and nerve root's functional change using the animal model of the chronic compressive injury in the nerve root. METHODS: The animal model of chronic compressive injury of the nerve root was established by transplanting autogenous cancellous bone into the intervertebral foramen. During different injury phase (1, 2, 4, 8, 12, 24 weeks after operation), the functional status of the nerve root was determined under the monitoring of evoked potential, and the expression changes of c-fos oncogene morphogenetic protein and nerve transmitter CGRP were detected using in situ hybridization technique and their expression intensity was determined using automatic image analytic instrument respectively. RESULTS: One week after operation, the c-fos expression strengthened in both anterior and posterior root fiber obviously. Two to four weeks after operation, the expression of the posterior root fiber weakened than the anterior root fiber. After 12 weeks, the anterior root fiber expression turned down obviously, however the posterior root fiber expression backed up slightly compared with that of the 8 weeks. By the time of 24 weeks after operation, the expression enhancement in all roots disappeared. CGRP expression increased obviously at the site of compressive axon of both anterior and posterior root. The expression of the posterior root axon and ganglion cell was higher than that of the anterior root axon. CGRP expression was diminished in the second week than the first week, and that was especially obvious in the posterior root and ganglion cell. But 4 weeks after operation, the expression enhanced once more, and that was more obvious inside the anterior root axon. Eight weeks after operation, the expression intensity attained the high peak. Twelve weeks after operation, the expression started the slow-moving descent. CONCLUSIONS: The expression of c-fos gene protein is beneficial to localize the damaged part of certain nerve. During chronic injury, the degeneration of posterior root sensory fiber is earlier than the anterior root motor fiber. The expression of CGRP strengthened when the nerve fiber degenerated by the harmful stimulation, and the expression intensity is positively related with pain. That suggests when the nervous tissue is hurt, the information of warning and regulation should be sent out to our body.

Animals↗
PubMed2004

Structure-based design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site.

A successful structure-based design of conformationally constrained second mitochondria-derived activator of caspase (Smac) mimetics that target the XIAP/caspase-9 interaction site is described. The most potent Smac mimetic 12d has a Ki of 350 nM for binding to the XIAP BIR3 domain protein. 12d is found to be effective in enhancing apoptosis induced by cisplatin in PC-3 human prostate cancer cells.

Amino Acid Motifs↗
PubMed2004

[Study on the optic neuropathy induced response protein gene mutation in Chinese patients with primary open-angle glaucoma].

OBJECTIVE: To screen the mutation loci of optic neuropathy induced response protein (OPTN) gene in Chinese with primary open-angle glaucoma (POAG) and to investigate the association between OPTN genotype and phenotype of POAG. METHODS: Specimens of peripheral blood were collected from Chinese 118 patients with POAG and 150 sex- and aged-matched subjects without POAG. Polymerase chain reaction (PCR) was used to analyze the coding sequence of OPTN gene consisting of thirteen exons. The abnormal strands by SSCP were evaluated by bi-directional sequencing. RESULTS: Eleven sequence changes were identified, 6 of which had been reported before (T34T, T49T, M98K, IVS6-SC-->T, IVS6-10G-->A, and R545Q), and 5 of which were novel (IVS6-9C-->T, IVS6-14G-->A, IVS7 + 36G-->A, IVS8-51T-->C, and K435R) Only K435R was found in patient with POAG, whereas IVS6-9C-->T and IVS6-14G-->A were present in control subjects. IVS6-5C-->T and IVS6-10G-->A showed significant association with POAG. The patients with IVS6-5C-->T sequence abnormality were aged 23 to 73 with an average intraocular pressure of 23.14 mm Hg (1 mm Hg =0. 133 kPa) and a mean defect of visual field 0.2 to 28. 2dB. The patients with IVS6-10C-->T sequence abnormality were aged 20 to 74 with an average intraocular pressure of 20.19 mm Hg and a mean defect of visual field from 0.9 to 26. 5dB. CONCLUSION: The single nucleotide polymorphism (SNP) of OPTN gene may contribute to the pathogenesis of glaucoma in Chinese.

Adolescent↗
PubMed2004

Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database.

The X-linked inhibitor of apoptosis (XIAP) is a promising new molecular target for the design of novel anticancer drugs aiming at overcoming apoptosis-resistance of cancer cells to chemotherapeutic agents and radiation therapy. Recent studies demonstrated that the BIR3 domain of XIAP where caspase-9 and Smac proteins bind is an attractive site for designing small-molecule inhibitors of XIAP. Through computational structure-based screening of an in-house traditional herbal medicine three-dimensional structure database of 8221 individual natural products, followed by biochemical testing of selected candidate compounds, we discovered embelin from the Japanese Ardisia herb as a small-molecular weight inhibitor that binds to the XIAP BIR3 domain. We showed that embelin binds to the XIAP BIR3 protein with an affinity similar to that of the natural Smac peptide using a fluorescence polarization-based binding assay. Our NMR analysis further conclusively confirmed that embelin interacts with several crucial residues in the XIAP BIR3 domain with which Smac and caspsase-9 bind. Embelin inhibits cell growth, induces apoptosis, and activates caspase-9 in prostate cancer cells with high levels of XIAP, but has a minimal effect on normal prostate epithelial and fibroblast cells with low levels of XIAP. In stably XIAP-transfected Jurkat cells, embelin effectively overcomes the protective effect of XIAP to apoptosis and enhances the etoposide-induced apoptosis and has a minimal effect in Jurkat cells transfected with vector control. Taken together, our results showed that embelin is a fairly potent, nonpeptidic, cell-permeable, small-molecule inhibitor of XIAP and represents a promising lead compound for designing an entirely new class of anticancer agents that target the BIR3 domain of XIAP.

Antineoplastic Agents↗
PubMed2004

Perceptual salience of global structures and the crowding effect in amblyopia.

BACKGROUND: The crowding effect refers to stronger deficits in linear acuity (e.g., letters in a line) than in single letter acuity in amblyopia. The current work investigated whether the salience of a global structure in which the target for identification is embedded influences the crowding effect in amblyopia. METHODS: Compound shapes were presented to the amblyopic and fellow eyes respectively of 12 anisometropic amblyopes. The compound stimuli were presented on either a blank or a cross background so that the salience of global structures were manipulated. Reaction times (RTs) and response error rates were recorded when subjects identified global or local shapes, respectively. RESULTS: RTs were shorter to global than local shapes for both the amblyopic and the fellow eyes. The global RT advantage was larger for the amblyopic than the fellow eye. Interestingly, when viewing the stimuli with the amblyopic eye, subjects made more errors to local targets when the compound stimuli were presented against the blank than the cross background. CONCLUSION: The results suggest that the salience of global structures of visual stimuli contributes to the crowding effect in amblyopia.

Adolescent↗
PubMed2004

Labeling and dynamic imaging of synaptic vesicle-like microvesicles in PC12 cells using TIRFM.

Total internal reflection fluorescence microscopy (TIRFM) was employed to study the trafficking and exocytosis of synaptic vesicle-like microvesicles (SLMVs) in PC12 cells. SLMVs were labeled with vesicular acetylcholine transporter (VAChT) tagged with enhanced green fluorescent protein (EGFP), which displayed punctuate distribution under TIRFM and confocal microscopy. Immunofluorescence analysis confirmed the colocalization of EGFP and VAChT. No significant difference was observed in the distribution or sorting of VAChT when fused either at the N- or the C-terminus. Thus, tagging with GFP does not appear to impair or change the traffic of the VAChT in PC12 cells. Under TIRFM, EGFP-labeled spots moved in a restrained fashion, which resembled that of secretory granules and underwent exocytosis upon stimulation. Together, these data indicate that EGFP-tagged VAChT can be used to explore SLMVs trafficking using TIRFM.

Animals↗
PubMed2004

[Experimental study on treatment of acute limb ischemia with vascular endothelial growth factor-121 gene transfer].

OBJECTIVE: To investigate the feasibility of intramuscular gene therapy for acute arterial ischemic diseases by use of plasmid pcDNA3-VEGF121 and to evaluate therapeutic efficiency of vascular endothelial growth factor (VEGF) by different routes of administration. METHODS: Fifty New Zealand White rabbits were randomly assigned to either gelation sponge carrying-pcDNA3-VEGF121 (n = 18), intramuscular injection-pcDNA3-VEGF121 (n = 18), or pcDNA3 (as control group, n = 14). After ligation of the external iliac artery and complete excision of the femoral artery, 500 micrograms of the plasmid pcDNA3-VEGF121 were transfected into the muscles of the ischemic limb by gelation sponge carrying or direct intramuscular-injection. Immediately after gene transfection, blood flow of the internal iliac artery were measured. VEGF121 gene expression was detected by RT-PCR after 2 days, 1 week, 2 weeks, 3 weeks and 4 weeks of transfection. After 30 days, blood flow of the internal iliac artery, angiographic score and histological vessels of ischemic hindlimbs were measured respectively. RESULTS: In the two VEGF-treated groups, VEGF121 mRNA expressed in the transfected ischemic muscles after 2 days and lasted 2 weeks. Immediately after gene transfection, blood flow of the internal iliac artery had no significant difference between three groups. After 30 days, blood flow of the internal iliac artery, angiographic score and capillary density were significantly greater in both VEGF-treated groups than in control group. Complexity of vascular branching and vessel density of gelation sponge-VEGF treated limbs were significantly greater when compared with the intramuscular-injection limbs. CONCLUSION: These findings suggest the feasibility of employing gene therapy of pcDNA3-VEGF121 could augment collateral development and tissue perfusion in an animal model of hindlimb ischemia, and gelation sponge carrying VEGF gene may respect a potential therapy methods.

Angiography↗
PubMed2004

[The prevalence and its screening methods of primary open angle glaucoma in defined population-based study of rural and urban in Beijing].

OBJECTIVE: The purpose of the study is to determine the prevalence of primary open-angle glaucoma (POAG) in persons aged 40 or above in Beijing, China. METHODS: From June 2001 to October 2001, the screening population was identified by a door-to-door census in five metropolitan resident areas in the north of Beijing and three villages in a county south to Beijing. The screening included visual acuity, frequency doubling perimetry (FDP, C-20 screening program), non-contact tonometry, slit lamp microscopy, anterior chamber depth (Van Herick method), and fundus photography. The suspect glaucoma and definite glaucoma patients were asked to have an examination of Octopus 1-2-3 perimetry (G1X TOP threshold program), repeat tonometry, gonioscopy and fundus stereo-photography at Beijing Tongren Hospital. RESULTS: There were 4451 subjects who were examined at the study sites. The response rates in rural and urban were 79.58% and 87.13%, respectively. In this 40 years-old or above population, the prevalences of POAG were 1.97% in rural men, 2.07% in urban men, 1.04% in rural women and 1.42% in urban women. In this study, 92.30% POAG patients in rural and 87.30% POAG patients in urban were new diagnosed cases. The prevalence of POAG increased with age and the change was exponential. In 50% POAG patients first IOP measurement was less than 21 mm Hg (1 mm Hg = 0.133 kPa). The prevalence of monocular eye blindness was 15.40% and 10.90% in rural and urban, respectively. CONCLUSIONS: Owing to use fundus photography and integrated evaluation of optic disc, it is possible to diagnose in earlier stage of POAG. This study identifies more patients with POAG than any previous population-based studies of China, and is similar to other studies of Asia such as in India and Singapore. The reason of lower POAG prevalence in rural women than in urban may be that the anterior chamber depth of rural women is shallower than that of urban women. It may cause difficult to differentiate the chronic primary angle closure glaucoma from POAG at screening sites, so the part POAG patients may be included in primary angle closure glaucoma patients.

Adult↗
PubMed2003

[Prevalence of low vision and blindness in defined populations in rural and urban areas in Beijing].

OBJECTIVE: To investigate the prevalence and causes of low vision and blindness in Beijing residents aged 40 and over. METHODS: 4,451 residents aged 40 and over in 3 rural communities and 5 urban communities in Beijing underwent eye examination, including examination of distant and near visual acuity (VA), best corrected distant and near VA, pinhole VA, and visual field, slit lamp biomicroscopy, and dilated ocular examination in the form of in-home survey by defined population-based sampling. The medical history was surveyed too. The data were analyzed based on the criteria of the World Health Organization. RESULTS: The general prevalence rates of low vision and blindness were 0.99% (95% CI: 0.70-1.28) and 0.39% (95% CI: 0.21-0.57) respectively. The prevalence rate of low vision in females was 1.45%, 2.23 times that of males (0.65%) (OR: 1.97, 95% CI: 1.00-3.95). The prevalence rate of low vision of rural residents was 1.76%, 2.89 times that of urban residents (0.61%) (OR: 2.93, 95% CI: 1.43-6.11). The prevalence rate of blindness in females was 0.64% and 0.37% in males. The prevalence rate of blindness of rural residents was 1.06%, 2.04 times that of the urban residents (0.52%) (OR: 3.77, 95% CI: 1.41-10.62). The 3 major causes of blindness were cataract (37.50%), glaucoma (29.20%), and high myopic macular degeneration (8.30%). The prevalence of blindness increased with age. CONCLUSION: The prevalence rates of low vision and blindness are higher in the rural areas. Cataract, glaucoma, and high myopic macular degeneration are the major causes of blindness. The prevalence of low vision and blindness are influenced by age, sex; area, health care level, educational level, and environmental factors.

Adult↗
PubMed2003

Chromium(VI) oxide catalyzed oxidation of sulfides to sulfones with periodic acid.

A highly efficient and selective oxidation of sulfides to sulfones with periodic acid catalyzed by CrO(3) is described. A variety of electron-rich and electron-deficient sulfides were oxidized to sulfones with 2 mol % CrO(3) in acetonitrile at room temperature in excellent yields. Sulfides with other readily oxidized functional groups were selectively oxidized to sulfones in high yields with 10 mol % CrO(3) in ethyl acetate/acetonitrile at -35 degrees C.

Journal Article↗
PubMed2003

Local influence analysis of structural equation models with continuous and ordinal categorical variables.

This paper proposes a method to assess the local influence of minor perturbations for a structural equation model with continuous and ordinal categorical variables. The key idea is to treat the latent variables as hypothetical missing data and then apply Cook's approach to the conditional expectation of the complete-data log-likelihood function in the corresponding EM algorithm for deriving the normal curvature and the conformal normal curvature. Building blocks for achieving the diagnostic measures are computed via observations generated by the Gibbs sampler. It is shown that the proposed methodology is relatively simple to implement, computationally efficient, and feasible for a wide variety of perturbation schemes. Two illustrative real examples are presented.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Dynamic imaging of single secretory granule in cultured PC12 cells.

Fluorescent labeling and dynamic imaging of secretory vesicles are new powerful means to study the mechanisms of protein and membrane trafficking. The large dense-core granules in PC12 cells were labeled by transfecting EGFP-hpNPY chimera and imaged with epi-fluorescence and evanescent field (EF) fluorescence simultaneously. Under epi-fluorescence illumination, the cells exhibited nearly uniform fluorescence, however, EF-fluorescence excitation revealed distinct fluorescent spots corresponding to GFP-labeled granules. The trafficking, docking and fusing with plasma membrane of individual granule in cultured PC12 cells were observed directly by EF fluorescence imaging.

Animals↗
PubMed2003

[The application of digital photography with retroillumination for lens in cataract study].

OBJECTIVE: To evaluate the reliability of digital photography with retroillumination for lens as a tool to assess the degree of lens opacity, and to study the morphological features of some lens diseases using the digital images. METHODS: The cataract screener (Neitz CT-S) was connected to a computer capable of acquiring digital images of lens. The digital lens retroillumination and slit lamp images were collected in 64 eyes. Three independent separate examiners took three sets of different CT-S digital photographs in four cataract subjects. The area of lens opacification in the images was measured and analyzed using threshold adjustment in PhotoShop software and a customized program in Matlab software. RESULTS: The distinct digital images of lens cortical opacity, posterior subcapsular opacity and other lens diseases were obtained with CT-S computer digital photography, which images were much better than slit lamp sectional digital images. The sensitivity and specificity of measuring lens opacification with CT-S digital images were 90% and 94% respectively. However, the digital lens retroillumination images were not as sensitive as the slit lamp images for nuclear cataracts. The variation coefficients of lens opacity area in the three sets of CT-S digital images in the same subject, which were taken by the independent examiners, were from 2.23% to 10.86%. The cortical opacification in CT-S digital images was linear, cuniform or clustered aggregate shadow configuration. The posterior subcapsular opacification was discal vacuolar or granular appearance. CONCLUSIONS: The reproducibility of the CT-S digital images taken by the independent examiners is excellent. This technique can objectively show cortical or posterior subcapsular opacities, but nuclear cataracts.

Adult↗