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Biomedical subjects

Xue Li

Publications and source records attributed to Xue Li.

At least 37 records · Page 2Linked to original sources

Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.

While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-dependent regulation of cell-lineage determination based on interactions between beta-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. beta-catenin acts as a binary switch to simultaneously activate expression of the critical lineage-determining transcription factor, Pit1, and to repress the gene encoding the lineage-inhibiting transcription factor, Hesx1, acting via TLE/Reptin/HDAC1 corepressor complexes. The strategy of functionally distinct actions of a homeodomain factor in response to Wnt signaling is suggested to be prototypic of a widely used mechanism for generating diverse cell types from pluripotent precursor cells in response to common signaling pathways during organogenesis.

Animals↗

Optimization and use of peptide mass measurement accuracy in shotgun proteomics.

Mass spectrometers that provide high mass accuracy such as FT-ICR instruments are increasingly used in proteomic studies. Although the importance of accurately determined molecular masses for the identification of biomolecules is generally accepted, its role in the analysis of shotgun proteomic data has not been thoroughly studied. To gain insight into this role, we used a hybrid linear quadrupole ion trap/FT-ICR (LTQ FT) mass spectrometer for LC-MS/MS analysis of a highly complex peptide mixture derived from a fraction of the yeast proteome. We applied three data-dependent MS/MS acquisition methods. The FT-ICR part of the hybrid mass spectrometer was either not exploited, used only for survey MS scans, or also used for acquiring selected ion monitoring scans to optimize mass accuracy. MS/MS data were assigned with the SEQUEST algorithm, and peptide identifications were validated by estimating the number of incorrect assignments using the composite target/decoy database search strategy. We developed a simple mass calibration strategy exploiting polydimethylcyclosiloxane background ions as calibrant ions. This strategy allowed us to substantially improve mass accuracy without reducing the number of MS/MS spectra acquired in an LC-MS/MS run. The benefits of high mass accuracy were greatest for assigning MS/MS spectra with low signal-to-noise ratios and for assigning phosphopeptides. Confident peptide identification rates from these data sets could be doubled by the use of mass accuracy information. It was also shown that improving mass accuracy at a cost to the MS/MS acquisition rate substantially lowered the sensitivity of LC-MS/MS analyses. The use of FT-ICR selected ion monitoring scans to maximize mass accuracy reduced the number of protein identifications by 40%.

Calibration↗

A class of self-stabilizing MCA learning algorithms.

In this letter, we propose a class of self-stabilizing learning algorithms for minor component analysis (MCA), which includes a few well-known MCA learning algorithms. Self-stabilizing means that the sign of the weight vector length change is independent of the presented input vector. For these algorithms, rigorous global convergence proof is given and the convergence rate is also discussed. By combining the positive properties of these algorithms, a new learning algorithm is proposed which can improve the performance. Simulations are employed to confirm our theoretical results.

Algorithms↗

Critical assessment of quantum mechanics based energy restraints in protein crystal structure refinement.

A critical evaluation of the performance of X-ray refinement protocols using various energy functions is presented using the bovine pancreatic trypsin inhibitor (BPTI) protein. The four potential energy functions we explored include: (1) fully quantum mechanical calculations; (2) one based on an incomplete molecular mechanics (MM) energy function employed in the Crystallography and NMR System (CNS) with empirical parameters developed by Engh and Huber (EH), which lacks electrostatic and attractive van der Waals terms; (3) one based on a complete MM energy function (AMBER ff99 parameter set); and (4) the same as 3, with the addition of a Generalized Born (GB) implicit solvation term. The R, R (free), real space R values of the refined structures and deviations from the original experimental structure were used to assess the relative performance. It was found that at 1 Angstrom resolution the physically based energy functions 1, 3, and 4 performed better than energy function 2, which we attribute to the better representation of key interactions, particularly electrostatics. The observed departures from the experimental structure were similar for the refinements with physically based energy functions and were smaller than the structure refined with EH. A test refinement was also performed with the reflections truncated at a high-resolution cutoff of 2.5 Angstrom and with random perturbations introduced into the initial coordinates, which showed that low-resolution refinements with physically based energy functions held the structure closer to the experimental structure solved at 1 Angstrom resolution than the EH-based refinements.

Animals↗

[Clinical study of use of laser fluorescence for detecting occlusal caries in deciduous teeth].

OBJECTIVE: To evaluate the distribution of DIAGNOdent value according to varying clinical caries severity. METHODS: A total of 541 deciduous molar teeth in children aged from 5 to 6 were examined using DIAGNOdent by one trained dentist. The most severity site in every tooth was recorded. The same sites were examined visually by another dentist. The distribution regular of DIAGNOdent value was analyzed according to the clinical severity score by Ekstrand index. RESULTS: The higher the visual score, the higher the mean DIAGNOdent value. The variation of values in each visual category was larger than that of values recommended by manufacturers. When clinical severity score was 0, 1, 2, 3 and 4, the median of DIAGNOdent value was 0, 5, 19, 49 and 99 respectively. The mean value for sound surfaces was lower in primary teeth than the cut-off points recommended by manufacturers, but the value of DIAGNOdent was increased obviously when the transparency change of enamel was detected visually. CONCLUSION: DIAGNOdent is useful in detecting occlusal caries in deciduous teeth, but the cut-off levels is not coinciding perfectly with manufacturer suggesting.

Child↗

[Research on dynamic and synchronous changes of microcirculatory ultrastructure and free radical in rat cerebrum after exhaustive swimming].

This research is designed to detect the dynamic changes of microcirculatory ultrastructure and the MDA content, SOD and GSH-px activity in rat cerebrum immediately, 24h and 48h after exhaustive swimming. The results showed that there were obvious changes of ultrastructure in rat cerebral microcirculation immediately after exhaustive swimming. The changes were resumed in some degree after 24h and recovered almost to the normal after 48h. Immediately after exhaustive swimming, the MDA content did not change obviously; the activity of SOD increased markedly, and then it decreased markedly after 24h, but it increased again after 48h. The activity of GSH-px descended markedly after 24h; it descended synchronously with the decrease of SOD activity, showing that the consumption of SOD and GSH-px should be the most at this time. Therefore, the free radical should be removed in time for reducing the cerebral injury and promoting the recovery of cerebral microcirculation.

Animals↗

[Relationship between the malignant mesothelioma and simian virus 40 in China: a study of 17 cases].

OBJECTIVE: To investigate whether simian virus 40 (SV40) was related to patients of malignant mesothelioma in China. METHODS: Paraffin-embeded samples of 17 patients with malignant mesothelioma were collected. After isolation of DNA from paraffin blocks, polymerase chain reaction (PCR) analyses were performed using three different sets of primer for detection of SV40 large T antigen gene. These samples were also immunohistochemically evaluated for expression of SV40 TAg protein with two different anti-SV40 Tag (Pab101 and Ab-2). RESULTS: Only one of the three primer pairs successfully amplified SV40 genome in three malignant mesothelioma samples. No immunopositive staining for SV40 TAg was found in any of the samples. CONCLUSIONS: The study shows that malignant mesothelioma in China may be independent of SV40 infection.

Adult↗

Polymer surfaces with reversibly switchable ordered morphology.

Honeycomb macroporous films fabricated by the "breath figures" method were composed of poly2-vinylpyridine (P2VP) distributed in the holes of polystyrene (PS). The porous films exhibited reversible behavior responding to water and different solvent vapors. When the porous film was treated with water, the honeycomb pattern would change to the hexagonal islandlike pattern. Once heated to remove the water, the honeycomb pattern emerged again. When the porous film was exposed to different solvent vapors, the same reversible process appeared. Carbon disulfide (CS(2)), toluene (TOL), and tetrahydrofuran (THF) solvent vapors induced the honeycomb pattern into the ordered islandlike pattern, and ethanol, chloroform, methyl ethyl ketone (MEK), and dimethylformamide (DMF) solvent vapors made the islandlike pattern come back to the honeycomb pattern. The hygroscopic property of P2VP and the polymer-solvent interaction are the driving force for the reversibly switchable morphology. The appropriate control of the hole depth is very crucial in determining the reversible changes.

Journal Article↗

One-step route to the fabrication of highly porous polyaniline nanofiber films by using PS-b-PVP diblock copolymers as templates.

We report a new method to control both the nucleation and growth of highly porous polyaniline (PANI) nanofiber films using porous poly(styrene-block-2-vinylpyridine) diblock copolymer (PS-b-P2VP) films as templates. A micellar thin film composed of P2VP spheres within a PS matrix is prepared by spin coating a PS-b-P2VP micellar solution onto substrates. The P2VP domains are swollen in a selective solvent of acetic acid, which results in the formation of pores in the block copolymer film. PANI is then deposited onto the substrates modified with such a porous film using electrochemical methods. During the deposition, the nucleation and growth of PANI occur only at the pores of the block copolymer film. After the continued growth of PANI by the electrochemical deposition, a porous PANI nanofiber film is obtained.

Journal Article↗

Vasculoprotective effect of insulin in the ischemic/reperfused canine heart: role of Akt-stimulated NO production.

OBJECTIVES: The objectives of this study were to investigate the vasculoprotective effects of glucose-insulin-potassium (GIK) on ischemia/reperfusion-induced coronary endothelial functional injury and to elucidate the mechanism involved. METHODS: Dogs were subjected to 50 min of coronary occlusion and 4 h of reperfusion. Vehicle, GIK, or GK were intravenously infused 5 min before reperfusion, and the coronary vascular dysfunction and endothelial apoptosis were determined. In a separate study, cultured endothelial cells were subjected to simulated ischemia/reperfusion, and the signaling pathway involved in insulin's anti-apoptotic effect was investigated. RESULTS: In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium-dependent vasorelaxation, decreased nitric oxide (NO) production, and endothelial cell apoptosis as determined by caspase 3 activation and TUNEL staining. Treatment with GIK, but not GK, markedly improved the endothelium-dependent coronary vasorelaxation (P<0.01 versus vehicle), increased total NO production (P<0.01), and attenuated endothelial apoptosis. In cultured endothelial cells, treatment with insulin also markedly increased NO production and reduced simulated ischemia/reperfusion-induced apoptosis. Moreover, pre-treatment with either Akt inhibitor or NO synthase inhibitor almost abolished the anti-apoptotic effect exerted by insulin but not by SNAP, an NO donor. CONCLUSION: These results demonstrate that in vivo treatment with GIK at reperfusion attenuates ischemia/reperfusion-induced coronary endothelial dysfunction and endothelial apoptosis in an Akt-dependent and NO-mediated fashion. The coronary vasculoprotective effect elicited by insulin may contribute to the previously observed cardiac protective effect of GIK.

Acetylcholine↗

High-density arrays of titania nanoparticles using monolayer micellar films of diblock copolymers as templates.

Highly dense arrays of titania nanoparticles were fabricated using surface micellar films of poly(styrene-block-2-vinylpyridine) diblock copolymers (PS-b-P2VP) as reaction scaffolds. Titania could be introduced selectively within P2VP nanodomains in PS-b-P2VP films through the binary reaction between water molecules trapped in the P2VP domains and the TiCl(4) vapor precursors. Subsequent UV exposure or oxygen plasma treatment removed the organic matrix, leading to titania nanoparticle arrays on the substrate surface. The diameter of the titania domains and the interparticle distance were defined by the lateral scale present in the microphase-separated morphology of the initial PS-b-P2VP films. The typical diameter of titania nanoparticles obtained by oxygen plasma treatment was of the order of approximately 23 nm. Photoluminescence (PL) properties were investigated for films before and after plasma treatment. Both samples showed PL properties with major physical origin due to self-trapped excitons, indicating that the local environment of the titanium atoms is similar.

Journal Article↗

Association between endogenous gene expression and growth regulation induced by TGF-beta1 in human gastric cancer cells.

AIM: To investigate the association between endogenous gene expression and growth regulation including proliferation and apoptosis induced by transforming growth factor-beta1 (TGF-beta1) in human gastric cancer (GC) cells. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the main components of the TGF-beta1/Smads signal pathway in human poorly differentiated GC cell line BGC-823. Localization of Smad proteins was also determined using immunofluorescence. Then, the BGC-823 cells were cultured in the presence or absence of TGF-beta1 (10 ng/mL) for 24 and 48 h, and the effects of TGF-beta1 on proliferation and apoptosis were measured by cell growth curve and flow cytometry (FCM) analysis. The ultrastructural features of BGC-823 cells with or without TGF-beta1 treatment were observed under transmission electron microscope. The apoptotic cells were visualized by means of the terminal deoxynucleotidyl transferase (TdT)-mediated dTUP in situ nick end-labeling (TUNEL) method. Meanwhile, the expression levels of endogenous p15, p21 and Smad7 mRNA and the corresponding proteins in the cells were detected at 1, 2 and 3 h after culture in the presence or absence of TGF-beta1 (10 ng/mL) by semi-quantitative RT-PCR and Western blot, respectively. RESULTS: The TGF-beta1/Smad signaling was found to be intact and functional in BGC-823 cells. The growth curve revealed the most evident inhibition of cell proliferation by TGF-beta1 at 48 h, and FCM assay showed G1 arrest accompanied with apoptosis induced by TGF-beta1. The typical morphological changes of apoptosis were observed in cells exposed to TGF-beta1. The apoptosis index (AI) in TGF-beta1-treated cells was significantly higher than that in the untreated controls (10.7+/-1.3% vs 0.32+/-0.06%, P<0.01). The levels of p15, p21 and Smad7 mRNA and corresponding proteins in cells were significantly up-regulated at 1 h, but gradually returned to basal levels at 3 h following TGF-beta1 (10 ng/mL) treatment. CONCLUSION: TGF-beta1 affects both proliferation and apoptosis of GC cells through the regulation of p15 and p21, and induces transient expression of Smad 7 as a negative feedback modulation of TGF-beta1 signal. Our results suggest a novel functional role of p21 as an accelerant of TGF-beta1-mediated apoptosis in GC cells.

Adenocarcinoma↗

Characterization of peptide folding nuclei by hydrogen/deuterium exchange-mass spectrometry.

Covalently linked pairs of well-chosen peptides can be good model systems for protein folding studies because they can adopt stable secondary, side-chain, and tertiary structure under certain conditions. We demonstrate a method for characterizing the structure in such peptide pairs by hydrogen/deuterium exchange of individual amide groups analyzed by collision-induced dissociation tandem mass spectrometry, in concert with circular dichroism spectroscopy. We apply the method to two peptides (and their three possible pairs) from bovine pancreatic trypsin inhibitor to address specific hypotheses regarding the stabilization of local secondary structure by long-range interactions.

Amides↗

[General pharmacology of Danhong injection].

OBJECTIVE: To investigate the effect of Danhong injection on the cardiovascular, the respiratory, and the nervous systems in animals. METHODS: Using the pressure transducer, tension transducer and subcutaneous electrodes connected to a multifunctional signal processor, the femoral artery pressure, respiratory curve and electrocardiogram were recorded, respectively, in dogs before and after administration of Danhong injection. The effect of the injection on spontaneous activities was observed in mice using a multifunctional mouse activity recorder. The effects were also observed on coordinated movements by recording tilt-board falling times of the mice and on hypnosis induced by subthreshold dose of pentobarbital sodium by observing the disappearance of righting reflex. RESULTS: Danhong injection caused slight decrease in systolic blood pressure without obviously affecting the heart rate, diastolic blood pressure and respiratory system of anesthetized dogs 30 min after intravenous Danhong injection at the dose of 2.4 g/kg, but at the doses of 1.2 and 0.6 g/kg.b.w, the injection did not produce any significant impact. The coordinated movement and spontaneous activity and pentobarbital sodium-induced hypnosis in mice were not obviously affected by the 3 doses of Danhong injection. CONCLUSION: Danhong injection does not affect the respiratory functions of the dogs and nervous system of mouse with the exception of the systolic pressure at the 3 doses.

Animals↗

[Oral health knowledge, attitude and behavior in adults of Deyang city, PR China].

OBJECTIVE: To investigate the oral health knowledge, attitudes and behavior of urban, rural and suburban adults in Deyang, PR China, and analyze the influence of several variables on the utilization of dental services. METHODS: 1010 adults with 35-44 years old from urban, rural and suburban areas were interviewed by Questionnaire for Adults, WHO Integrated Package for Basic Oral Care. RESULTS: More than half of the surveyed adults claimed "having pain of mouth during the last 1 year". More urban adults (61.3%) used fluoridate toothpaste than suburban and rural adults (6.9%, 16.8%). 61.0% and 71.5% of rural and suburban adults had never seen a dentist, compared with 32.0% of urban adults. Logistic regression analysis showed that urban adults having pain in mouth during the last year were more likely to visit a dentist in the last 2 years. CONCLUSION: Although the oral health attitude is good among the people in Deyang, the knowledge is poor. Dental service utilization was not enough and the situation was also worse for rural adults.

Adult↗

[Variety of differential display on gene and corresponding gene's clone following corneal alkali burns in rats].

OBJECTIVE: To study the condition of differential gene caused after corneal alkali burns in rats and clarify the molecular biological foundation of corneal denatured protein. METHODS: The animals were sacrificed on the 3rd day and the 2nd week after alkali burns. Total RNA was isolated from the excised corneas and then reverse-transcribed into cDNA. The differential gene was detected by mRNA differential display reverse transcription polymerase chain reaction (DDRT-PCR) with two kinds of anchoring primer and 12 kinds of random primers after corneal alkali burns in the rats. The differential gene fragments were cloned, and their homogeneity was compared with each other in the Gene Bank. RESULTS: Compared with the normal cornea, the cornea of alkali burns on the 2nd week produced one differential gene fragment of 630 bp in the same reaction condition, and this differential gene was homologous to the rattus norvegicus mitochondrial cytochrome oxidase subunits I, II, III gene. CONCLUSIONS: It is found that there is differential gene in the cornea of alkali burns on the 2nd week in rats, and this differential gene is homologous to the rattus norvegicus mitochondrial cytochrome oxidase subunits I, II, III gene. It can be concluded that the occurrence of this differential gene is possible to be related with the action of the superoxide free radicals caused by alkali burns.

Animals↗

Effects of phosphorothioate anti-sense oligodeoxynucleotides on colorectal cancer cell growth and telomerase activity.

AIM: To investigate the inhibitory effect of phosphorothioate anti-sense oligodeoxynucleotides (PASODN) on colorectal cancer LS-174T cells in vitro and the mechanism of inhibition of telomerase activity in these cells. METHODS: PASODN were used to infect LS-174T cells and block human telomerase RNA (hTR) through anti-sense technology. The inhibitory effect of PASODN was evaluated by colony-forming inhibition assay and growth curve. Changes of telomerase activity in LS-174T cells were detected by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), and the level of apoptosis was analyzed by flow cytometry (FCM) assay. RESULTS: PASODN showed a dose and time-dependent inhibition of cell proliferation. The optimal dosage of PASODN was 10 mumol/L. The colony-forming efficiency was 10.3% in PASODN group after 10 d, whereas that in phosphorothioate mis-sense oligodeoxynucleotides (PMSODN) group with the same concentration and in PBS group (blank control) was 49.1% and 50.7%, respectively. PCR-ELISA results indicated that telomerase activity in the PASODN group was obviously inhibited in comparison with in the control groups (P<0.01, t = 3.317 and 3.241, t0.01(20) = 2.845). Meanwhile, before the number of cells was decreased, the morphological changes were observed in the cells of PASODN group. The cells in PASODN group showed the apoptotic peak at 72 h after infection, whereas the control group did not show. CONCLUSION: Specific sequence oligonucleotides can inhibit telomerase activity and lead to cell apoptosis, suggesting a novel treatment strategy for malignant tumors induced by telomerase.

Apoptosis↗