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Liang Dong

Publications and source records attributed to Liang Dong.

At least 19 recordsLinked to original sources
PubMed2007

Screening method to identify preclinical liquid and semi-solid formulations for low solubility compounds: miniaturization and automation of solvent casting and dissolution testing.

We have developed an efficient screening method to identify liquid and semisolid formulations for low-solubility compounds. The method is most suitable for identifying dosing vehicles for compounds in lead optimization, where compound supply is limited and long-term stability is not a requirement. Dilute compound and excipient stock solutions are prepared in organic solvent and then dispensed and mixed in 96-well plates. The solvent is removed in a vacuum centrifuge evaporator, leaving neat formulation (e.g., 10-40 microg compound, 0.4 mg excipient) at the bottom of each well. After an aging step, an aqueous dilution medium is added and the plates are incubated (agitation by orbital shaking). The diluted formulations are then filtered and analyzed by ultraviolet (UV) absorbance or high-performance liquid chromatography (HPLC). To illustrate the method, two compounds (aqueous solubility </=1 microg/mL) were combined with eight solubilizing excipients, at four drug-loading levels (25, 50, 75, and 100 mg/g) and three incubation times (0.5, 2, and 24 h). This allowed identification of the excipients and loading levels, which generated the highest and most stable kinetic solubility upon dilution. The peak kinetic solubility was strongly correlated with the equilibrium solubility. Application of the method to screening compound/surfactant/oil formulations is also presented.

Chemistry, Pharmaceutical↗
PubMed2006

Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells.

Cigarette smoke is a complex mixture of more than 4700 chemical compounds including free radicals and oxidants. Toxicity exhibited by cigarette smoke may be due to combined action of these compounds inducing many cellular processes mediated through reactive oxygen species (ROS). Major player probably nicotine as it is present in tobacco, in higher concentrations. The compounds that induce intracellular oxidative stress recognized as the important agents involved in the damage of biological molecules. Experiments using animal and cell culture model systems suggested that moderately higher concentrations of some forms of ROS like NO and H(2)O(2) can act as signal transducing agents. Nuclear transcription factor kappaB (NF-kappaB) an inducible transcription factor detected in neurons found to be involved in many biological processes such as inflammation, innate immunity, development, apoptosis, and antiapoptosis. Our present study demonstrates that nicotine induces ROS levels in a dose dependent manner in rat mesencephalic cells. Electro mobility shift analysis showed that nicotine activates inducible NF-kappaB by binding to consensus sequence of DNA. Nicotine added to cell culture stimulates the degradation of IkappaB-alpha subunit in 2 h. Further activation of c-Jun terminal kinase indicates that nicotine induces oxidative stress leading to activation of stress dependent NF-kappaB pathway in mesencephalic cells.

Animals↗
PubMed2006

Catalytic mechanism of endonuclease v: a catalytic and regulatory two-metal model.

The enzyme endonuclease V initiates repair of deaminated DNA bases by making an endonucleolytic incision on the 3' side one nucleotide from a base lesion. In this study, we have used site-directed mutagenesis to characterize the role of the highly conserved residues D43, E89, D110, and H214 in Thermotoga maritima endonuclease V catalysis. DNA cleavage and Mn(2+)-rescue analysis suggest that amino acid substitutions at D43 impede the enzymatic activity severely while mutations at E89 and D110 may be tolerated. Mutations at H214 yield enzyme that maintains significant DNA cleavage activity. The H214D mutant exhibits little change in substrate specificity or DNA cleavage kinetics, suggesting the exchangeability between His and Asp at this site. DNA binding analysis implicates the involvement of the four residues in metal binding. Mn(2+)-mediated cleavage of inosine-containing DNA is stimulated by the addition of Ca(2+), a metal ion that does not support catalysis. The effects of Mn(2+) on Mg(2+)-mediated DNA cleavage show a complexed initial stimulatory and later inhibitory pattern. The data obtained from the dual metal ion analyses lead to the notion that two metal ions are involved in endonuclease V-mediated catalysis. A catalytic and regulatory two-metal model is proposed.

Amino Acid Substitution↗
PubMed2006

Adaptive liquid microlenses activated by stimuli-responsive hydrogels.

Despite its compactness, the human eye can easily focus on different distances by adjusting the shape of its lens with the help of ciliary muscles. In contrast, traditional man-made optical systems achieve focusing by physical displacement of the lenses used. But in recent years, advances in miniaturization technology have led to optical systems that no longer require complicated mechanical systems to tune and adjust optical performance. These systems have found wide use in photonics, displays and biomedical systems. They are either based on arrays of microlenses with fixed focal lengths, or use external control to adjust the microlens focal length. An intriguing example is the tunable liquid lens, where electrowetting or external pressure manipulates the shape of a liquid droplet and thereby adjusts its optical properties. Here we demonstrate a liquid lens system that allows for autonomous focusing. The central component is a stimuli-responsive hydrogel integrated into a microfluidic system and serving as the container for a liquid droplet, with the hydrogel simultaneously sensing the presence of stimuli and actuating adjustments to the shape--and hence focal length--of the droplet. By working at the micrometre scale where ionic diffusion and surface tension scale favourably, we can use pinned liquid-liquid interfaces to obtain stable devices and realize response times of ten to a few tens of seconds. The microlenses, which can have a focal length ranging from -infinity to +infinity (divergent and convergent), are also readily integrated into arrays that may find use in applications such as sensing, medical diagnostics and lab-on-a-chip technologies.

Biomedical Engineering↗
PubMed2006

Dual optical and nuclear imaging in human melanoma xenografts using a single targeted imaging probe.

INTRODUCTION: Dual-labeled imaging agents that allow both nuclear and optical imaging after a single injection would be advantageous in certain applications. In this study, we synthesized and characterized a dual-labeled RGD (Arg-Gly-Asp) peptide and compared nuclear and optical images obtained with this agent. METHODS: 111In-DTPA-Lys(IRDye800)-c(KRGDf) composed of both the 111In chelator diethylenetriaminepentaacetic acid (DTPA) and the near-infrared (NIR) fluorescent dye IRDye800 (excitation/emission, 765/792 nm) was synthesized. The probe was characterized with regard to in vitro biological activity and in vivo pharmacokinetics and the ability to target integrin alphavbeta3. Tumors of mice injected with the dual-labeled probe were imaged both by gamma scintigraphy and NIR fluorescence optical camera. RESULTS: DTPA-Lys(IRDye800)-c(KRGDf), DTPA-Lys-c(KRGDf) and c(KRGDf) inhibited the adhesion of melanoma M21 cells to vitronectin-coated surface with the similar biological activity. Both 111In-DTPA-Lys(IRDye800)-c(KRGDf) and 111In-DTPA-Lys-c(KRGDf) had significantly higher uptakes in alphavbeta3-positive M21 melanoma than in alphavbeta3-negative M21-L melanoma at 4-48 h after their injection. Side-by-side comparison of images obtained using 111In-DTPA-Lys(IRDye800)-c(KRGDf) revealed that in living mice, both optical imaging and gamma scintigraphy enabled noninvasive detection of the bound probe to alphavbeta3-positive tumors, with optical images providing improved resolution and sensitive detection of the superficial lesions and gamma images providing sensitive detection of deeper structures. CONCLUSION: The dual-labeled imaging probe 111In-DTPA-Lys(IRDye800)-c(KRGDf) was found to specifically bind to alphavbeta3 in melanoma tumor cells. Employing both nuclear and optical imaging with a single imaging probe may facilitate translation of NIR fluorescence optical imaging into clinical applications.

Animals↗
PubMed2006

Effects of sinusoidal magnetic field observed on cell proliferation, ion concentration, and osmolarity in two human cancer cell lines.

Low frequency magnetic fields have previously been shown to affect cell functions. In this article, the effects of 20 mT, 50 Hz sinusoidal magnetic field on cell proliferation, ion concentration, and osmolarity in two human cancer cell lines (HL-60 and SK-Hep-1) were investigated. Inhibition of cell growth was observed. On the other hand, the exposure also increased the Na+, K+ ion concentration and osmolarity in cell supernatant compared to the control group. To our knowledge, this is the first study on cancer cells where magnetic fields affect osmolarity in cell supernatant. In addition, a model of cells exposed to the oscillating magnetic field is described as well as the characteristics of ions in and out of cells. The experimental data appears to be consistent with the theoretical analysis. The results are also discussed in terms of the relationships among cell growth, ion concentration, and osmolarity. Magnetic field inhibitions of cell growth in vitro may relate to changes in cell ion concentration and osmolarity.

Cell Line, Tumor↗
PubMed2006

[A prospective, randomized, controlled trial of autologous mesenchymal stem cells transplantation for dilated cardiomyopathy].

OBJECTIVE: Recent experimental and clinical observations have suggested that cell transplantation could be of therapeutic value for the treatment of heart failure. This study was performed to explore the efficacy and safety of intracoronary autologous mesenchymal stem cells (MSCs) transplantation for treating patients with idiopathic dilated cardiomyopathy. METHOD: Twenty-four consecutive patients with idiopathic dilated cardiomyopathy received standard drug therapy were randomly divided into intracoronary injection of autologous mesenchymal stem cells (treated, n = 12) or saline (control, n = 12) groups. Serum IL-6, TNF-alpha and CRP, plasma brain natriuretic peptides (BNP) were determined and echocardiography, Holter electrocardiogram monitoring and six minutes walk test were performed at baseline, 3 and 6 months post injection. RESULTS: IL-6, TNF-alpha and CRP remained unchanged after MSCs transplantation. Plasma BNP levels at 3 months and 6 months post MSCs injection were significantly higher than that of pre-injection (378.10 +/- 147.47, 420.40 +/- 148.50 vs. 292.40 +/- 148.54 ng/L, respectively, P < 0.05) but were significantly lower than that in control group at comparable time points (3 months: 378.10 +/- 147.47 vs. 473.10 +/- 106.31 ng/L; 6 months: 420.40 +/- 148.50 vs. 544.60 +/- 93.11 ng/L, P < 0.05). Six-minute-walking distance significantly increased at 6 months after MSCs injection compared with pre-injection level and which is also higher than that in control patients (519.00 +/- 43.28 vs. 396.33 +/- 42.19 and 464.00 +/- 76.5 m, respectively, P < 0.05). Left ventricular ejection fraction and LVEDd remained unchanged post MSCs injection. No malignant arrhythmias and severe side effects could be observed around transplantation and during six months follow-up. Survival was similar between the two groups during six months follow-up. CONCLUSION: Percutaneous coronary autologous mesenchymal stem cells transplantation can attenuate the increase of plasma BNP, increase six-minute-walking capacity in patients with idiopathic dilated cardiomyopathy.

Aged↗
PubMed2005

Breaking the limit of maximum effective area for robust single-mode propagation in optical fibers.

We propose and demonstrate a novel approach in optical fiber design in which the optical waveguide is formed by a ring of large air holes surrounding a solid silica core. With an appropriate choice of the geometrical configuration, robust single-transverse-mode propagation with a record effective area of 1417 microm2, verified by various methods, was demonstrated. A breakthrough was made toward the development of practical ultra-high-power fiber lasers as we observed negligible loss of the fiber at bending diameters as small as 15 cm.

Journal Article↗
PubMed2005

Defining amino acid residues involved in DNA-protein interactions and revelation of 3'-exonuclease activity in endonuclease V.

Endonuclease V is an enzyme that initiates a conserved DNA repair pathway by making an endonucleolytic incision at the 3' side one nucleotide from a deaminated base lesion. Site-directed mutagenesis analysis was conducted at seven conserved motifs of the thermostable Thermotoga maritima endonuclease V to probe for residues that affect DNA-protein interactions. Y80, G83, and L85 in motif III, H116 and G121 in motif IV, A138 in motif V, and S182 in motif VI affect binding of both the double-stranded inosine-containing DNA substrate and the nicked double-stranded inosine-containing DNA product, resulting in multiple enzymatic turnovers. The substantially reduced DNA cleavage activity observed in G113 in motif IV and G136 in motif V can be partly attributed to their defect in metal cofactor coordination. Alanine substitution at amino acid 118 primarily reduces the level of binding to the nicked product, suggesting that R118 plays a significant role in postcleavage DNA-protein interaction. Binding and cleavage analyses of multiple mutants at positions Y80 and H116 underscore the role these residues play in protein-DNA interaction and implicate their potential involvement as a hydrogen bond donor in recognition of deaminated DNA bases. DNA cleavage analysis using mutants defective in DNA binding reveals a novel 3'-exonuclease activity in endonuclease V. An alternative model is proposed that entails lesion specific cleavage and endonuclease to 3'-exonuclease mode switch by endonuclease V for removal of deaminated base lesions during endonuclease V-mediated repair.

Amino Acid Sequence↗
PubMed2005

Randomized algorithms for motif detection.

MOTIVATION: Motif detection for DNA sequences has many important applications in biological studies, e.g. locating binding sites regulatory signals, designing genetic probes etc. In this paper, we propose a randomized algorithm, design an improved EM algorithm and combine them to form a software tool. RESULTS: (1) We design a randomized algorithm for consensus pattern problem. We can show that with high probability, our randomized algorithm finds a pattern in polynomial time with cost error at most x l for each string, where l is the length of the motif and can be any positive number given by the user. (2) We design an improved EM algorithm that outperforms the original EM algorithm. (3) We develop a software tool, MotifDetector, that uses our randomized algorithm to find good seeds and uses the improved EM algorithm to do local search. We compare MotifDetector with Buhler and Tompa's PROJECTION which is considered to be the best known software for motif detection. Simulations show that MotifDetector is slower than PROJECTION when the pattern length is relatively small, and outperforms PROJECTION when the pattern length becomes large. AVAILABILITY: It is available for free at http://www.cs.cityu.edu.hk/~lwang/software/motif/index.html, subject to copyright restrictions.

Algorithms↗
PubMed2005

Validation of the use of foreign gas rebreathing method for non-invasive determination of cardiac output in heart disease patients.

OBJECTIVE: To compare a new device (Innocor) for non-invasive measurement of cardiac output (CO) by foreign gas rebreathing method with conventional techniques used in the measurements of cardiac function. METHODS: Cardiac outputs measured by Innocor (CO(RB)) were compared with CO obtained by echocardiography (CO(EC)), Swan-Ganz thermodilution (CO(TD)), and left ventricle radiography (CO(LVR)) in 34 patients subjected to cardiac catheterization. Values obtained from the four methods were analyzed by linear regression and paired values were compared by the method of Bland and Altman in SPSS. RESULTS: There was strong positive correlation (r=0.94) between Innocor cardiac output values and the corresponding values obtained by thermodilution and between CO(EC) and CO(LVR) values. Thermodilution appears to overestimate cardiac output when compared to the values obtained with Innocor by (0.66+/-0.22) L/min (P<0.0001). There was no correlation between data obtained by Innocor and the corresponding CO(EC) and CO(LVR) values. CONCLUSION: Innocor CO(RB) is an easy, safe and well established method for non-invasive measurement of cardiac output with good prospects for clinical application in heart disease patients.

Adult↗
PubMed2005

[Tissue Doppler imaging evaluate the effect of optimal biventricular resynchronization for congestive heart disease in left ventricular synchrony and function].

OBJECTIVE: To evaluate the immediate change of left ventricular systolic performance and asynchronization between simultaneous biventricular pacing and sequential biventricular pacing by tissue synchronization imaging (TSI) and tissue velocity imaging (TVI) in patients with congestive heart failure. The effect of sequential biventricular resynchronization therapy was also observed. METHODS: Ten patients with dilated cardiomyopathy who received sequential biventricular resynchronization were enrolled. The TVI and TSI imagings were performed by GE vivid7 with M3S probe. The left ventricular ejection fraction (LVEF), stroke volume (SV), aortic velocity time integral (VTI), left ventricular end diastolic diameter (LVEDd), the standard deviation of the electro-mechanical delay (EMD-SD) of 6 segments and TSI index were measured before implanting of InSync 8042 and 1 month, 3 months, 6 months after implanting respectively. RESULTS: After 6 months of implanting, the LVEF, SV and VTI were obviously increased from (22.0 +/- 8.8)% to (38.0 +/- 9.9)%; (36.0 +/- 14.9) ml to (57.0 +/- 15.7) ml; (20.22 +/- 5.72) cm to (26.20 +/- 5.98) cm, P < 0.05, respectively, compared with the before of implanting. The LVEDd was decreased from (6.6 +/- 0.6) cm, to (6.0 +/- 0.9) cm, P < 0.05. The EMD-SD and TSI-index were declined gradually after implanting, which was more evident in the 6 months after implanting, from (83.07 +/- 46.99) ms to (22.37 +/- 16.38) ms; (2.20 +/- 0.36) to (1.50 +/- 0.43), P < 0.05, respectively, but the immediate EMD-SD did not change obviously between simultaneous biventricular pacing and sequential biventricular pacing, whereas, the TSI index and VTI were significantly improved from (1.87 +/- 0.31) to (1.71 +/- 0.29); (22.44 +/- 5.43) cm to (25.44 +/- 5.36) cm, P < 0.05, respectively, in the sequential biventricular pacing. CONCLUSION: Sequential biventricular resynchronization could improve the left ventricular systolic function and synchronism of wall motion in the patients with congestive heart failure, which is more effective than simultaneous biventricular pacing after implanting immediately.

Aged↗
PubMed2004

Oxanine DNA glycosylase activity from Mammalian alkyladenine glycosylase.

Oxanine (Oxa) is a deaminated base lesion derived from guanine in which the N(1)-nitrogen is substituted by oxygen. This work reports the mutagenicity of oxanine as well as oxanine DNA glycosylase (ODG) activities in mammalian systems. Using human DNA polymerase beta, deoxyoxanosine triphosphate is only incorporated opposite cytosine (Cyt). When an oxanine base is in a DNA template, Cyt is efficiently incorporated opposite the template oxanine; however, adenine and thymine are also incorporated opposite Oxa with an efficiency approximately 80% of a Cyt/Oxa (C/O) base pair. Guanine is incorporated opposite Oxa with the least efficiency, 16% compared with cytosine. ODG activity was detected in several mammalian cell extracts. Among the known human DNA glycosylases tested, human alkyladenine glycosylase (AAG) shows ODG activity, whereas hOGG1, hNEIL1, or hNEIL2 did not. ODG activity was detected in spleen cell extracts of wild type age-matched mice, but little activity was observed in that of Aag knock-out mice, confirming that the ODG activity is intrinsic to AAG. Human AAG can excise Oxa from all four Oxa-containing double-stranded base pairs, Cyt/Oxa, Thy/Oxa, Ade/Oxa, and Gua/Oxa, with no preference to base pairing. Surprisingly, AAG can remove Oxa from single-stranded Oxa-containing DNA as well. Indeed, AAG can also remove 1,N(6)-ethenoadenine from single-stranded DNA. This study extends the deaminated base glycosylase activities of AAG to oxanine; thus, AAG is a mammalian enzyme that can act on all three purine deamination bases, hypoxanthine, xanthine, and oxanine.

Animals↗
PubMed2004

Introduction of foreign genes into silkworm eggs by electroporation and its application in transgenic vector test.

Electroporation as a methodology to introduce foreign genes into silkworm eggs was systematically analyzed. The foreign gene in both the newly hatched and 3rd instar larva DNA can be detected by PCR. The amount of foreign gene in 3rd instar larva DNA was about 1/1000 of that in newly hatched larva DNA. The ratio of foreign gene entering into silkworm eggs was voltage dependent and showed significant difference between the tested silkworm strains. When the piggyBac transposon system was applied, the effect of nuclear localization signal (NLS) peptide and the in vitro transcribed transposase mRNA on the transposition rate has been measured. Results showed that the in vitro transcribed transposase mRNA facilitated transposition to take place earlier and NLS could result in higher transposition probability and earlier transposition as well. When linearized vectors containing varied length of flanking homologous sequences around a reporter gene were introduced into silkworm eggs by electroporation, the one with 2.6 kb total arm length gave higher G1 positive ratio than that with total arm length of 1.5 kb and 800 bp.

Animals↗
PubMed2004

Enhanced ileal absorption of a hydrophilic macromolecule, pentosan polysulfate sodium (PPS).

An in situ gelling, bioadhesive liquid formulation was developed to enhance the bioavailbility (BA) of a polysaccharide, pentosan polysulfate sodium (PPS). The formulation was tested to determine its bioavailability enhancement in a non-flush/non-ligated rat ileal model. A potent synergistic effect was found with a gelling agent Cremophor and a permeation enhancer sodium salicylate. The absolute bioavailabilities were 1.9%, 4.6%, 6.3% and 46.4%, respectively, for the PPS solution in saline, sodium salicylate/PPS, Cremophor/PPS and Cremophor/sodium salicylate/PPS. Therefore, we successfully demonstrated the approach of utilizing an in situ gelling/bioadhesive liquid carrier to enhancing the bioavailability of a hydrophilic macromolecule at the distal small intestine.

Animals↗
PubMed2003

Strong phase-controlled fiber Bragg gratings for dispersion compensation.

Dispersion-compensating fiber Bragg gratings with approximately 99.9% reflectivity that are made by continuous apodization and phase control are demonstrated. These strong dispersion-compensating gratings provide precision second-order, third-order, or even more complex dispersion compensation, as well as sufficient transmission isolation to be used at add-drop stages without additional filtering. A 99.84% grating with a constant approximately 700-ps/nm dispersion and a 99.94% grating with dispersion varying linearly from 1000 to -1000 ps/nm are demonstrated.

Journal Article↗
PubMed2003

[Production and application of rabbit anti-imitative spider dragline silk protein polyclonal antibody].

A synthetic spider dragline gene s600 was cloned into fusion protein expression vector pGEX-KG and expressed in Escherichia coli. Protein S600 was purified and rabbit antiserum was prepared. Amino acid composition analysis confirmed the right expression of S600. Western blot analysis revealed that anti-S600 antiserum could react with natural spider silk, so the synthetic dragline protein, designed by the authors, shares similar immunological characteristics with the natural spider silk. An ELISA system was also established for the quantitative detection of synthetic dragline protein expression in silk gland (or in the cocoon) of transgenic silkworm.

Animals↗