Biomedical subjects

Xiang Li

Publications and source records attributed to Xiang Li.

At least 73 records · Page 4Linked to original sources

PubMed2006

[Effect of vasoactive intestinal peptide and epidermal growth factor on the adhesion of eosinophils to bronchial epithelial cells].

OBJECTIVE: To investigate the effect of intrapulmonary regulatory peptides on adhesion of eosinophils (EOS) to bronchial epithelial cells (BECs). METHODS: Two regulatory peptides, namely vasoactive intestinal peptide (VIP) and epidermal growth factor (EGF) were investigated. VIP and EGF were observed on the secretion of ILs and expression of intercellular adhesion molecule-1 (ICAM-1). RESULTS: VIP and EGF could decrease ILs secretion and ICAM-1 expression. CONCLUSION: VIP and EGF inhibited the adhesion of EOS to BEC in the inflammatory process to lighten the airway inflammation.

Animals↗

PubMed2006

[Type IV collagenase expression in human prostate carcinoma cell lines with different metastasis potentials].

OBJECTIVE: To investigate the correlation between type IV collagenase expression and metastatic potential of human prostate carcinoma cells. METHODS: Human prostate carcinoma cell lines (LNCaP and C4-2B) with different metastatic potentials were selected. Using SABC immunocytochemical staining and zymographic analysis, we detected the difference of type IV collagenase expression and activity between the two cell lines. RESULTS: The expression of type IV collagenase (MMP-2, MMP-9) could be detected in both LNCaP and C4-2B, mainly in cytoplasm, much higher in C4-2B than in LNCaP (P < 0.01). The activities of type IV collagenase in the conditioned medium of prostatic carcinoma cell LNCaP was the lowest, and the quantitative estimation values of MMP-2 and MMP-9 were 0.89 +/- 0.02 and 0.86 +/- 0.01, respectively. However, the quantitative estimation values of MMP-2 and MMP-9 in the conditioned medium of C4-2B were 96.32 +/- 4.36 and 33.89 +/- 1.84, respectively. Compared with LNCaP, the activity of type IV collagenase in C4-2B was much higher (P < 0.01). CONCLUSION: Compared with LNCaP, the higher production capability of type IV collagenase in C4-2B may possibly contribute to its invasive and metastatic potentials. The expression of type IV collagenase of human prostate carcinoma cells is closely correlated to the metastatic and invasive potential.

Cell Line, Tumor↗

PubMed2006

[Autosomal dominant congenital golden crystal nuclear cataract caused by a missense mutation in gammaD crystallin gene (CRYGD) in a Chinese family].

OBJECTIVE: To identify genetic defects associated with autosomal dominant congenital golden crystal nuclear cataract (ADCC) in a Chinese pedigree of northern China. METHODS: Clinical data were collected and the lens changes of the affected members in this family were recorded by slit lamp photography. Genomic DNA was obtained from blood leucocytes. Linkage analyses was conducted using polymorphisms of 21 microsatellite markers and mutational analyses of candidate genes was studied by direct sequencing. RESULTS: The maximum LOD score (1.505 at recombination fraction theta = 0.00) was obtained at markers D2S1782, D2S1384 and D2S1385 near the gamma-crystallin gene (CRYG) cluster within 2q33 - q35. Sequencing analysis of the coding regions of the CRYGA. B, C, and D genes showed that the there was a heterozygous C-->A transversion at position 109 (R36S) in exon 2 of CRYGD gene, which was co-segregated with the affected members. CONCLUSIONS: R36S mutation in CRYGD gene results in an ADCC phenotype that is different from previous reports. This finding indicates that the presence of phenotypic heterogeneity of cataract, especially in different races. This is the first report of congenital cataract caused by R36S mutation in CRYGD gene.

Asian People↗

PubMed2005

Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin.

Techniques for fast noninvasive control of neuronal excitability will be of major importance for analyzing and understanding neuronal networks and animal behavior. To develop these tools we demonstrated that two light-activated signaling proteins, vertebrate rat rhodopsin 4 (RO4) and the green algae channelrhodospin 2 (ChR2), could be used to control neuronal excitability and modulate synaptic transmission. Vertebrate rhodopsin couples to the Gi/o, pertussis toxin-sensitive pathway to allow modulation of G protein-gated inward rectifying potassium channels and voltage-gated Ca2+ channels. Light-mediated activation of RO4 in cultured hippocampal neurons reduces neuronal firing within ms by hyperpolarization of the somato-dendritic membrane and when activated at presynaptic sites modulates synaptic transmission and paired-pulse facilitation. In contrast, somato-dendritic activation of ChR2 depolarizes neurons sufficiently to induce immediate action potentials, which precisely follow the ChR2 activation up to light stimulation frequencies of 20 Hz. To demonstrate that these constructs are useful for regulating network behavior in intact organisms, embryonic chick spinal cords were electroporated with either construct, allowing the frequency of episodes of spontaneous bursting activity, known to be important for motor circuit formation, to be precisely controlled. Thus light-activated vertebrate RO4 and green algae ChR2 allow the antagonistic control of neuronal function within ms to s in a precise, reversible, and noninvasive manner in cultured neurons and intact vertebrate spinal cords.

Animals↗

PubMed2005

Sphingosine kinase 1 is a negative regulator of CD4+ Th1 cells.

CD4+ Th1 cells produce IFN-gamma, TNF-alpha, and IL-2. These Th1 cytokines play critical roles in both protective immunity and inflammatory responses. In this study we report that sphingosine kinase 1 (SPHK1), but not SPHK2, is highly expressed in DO11.10 Th1 cells. The expression of SPHK1 in Th1 cells requires TCR signaling and new protein synthesis. SPHK1 phosphorylates sphingosine to form sphingosine-1-phosphate. Sphingosine-1-phosphate plays important roles in inhibition of apoptosis, promotion of cell proliferation, cell migration, calcium mobilization, and activation of ERK1/2. When SPHK1 expression was knocked down by SPHK1 short interfering RNA, the production of IL-2, TNF-alpha, and IFN-gamma by Th1 cells in response to TCR stimulation was enhanced. Consistently, overexpression of dominant-negative SPHK1 increased the production of IL-2, TNF-alpha, and IFN-gamma in Th1 cells. Furthermore, overexpression of SPHK1 in Th1 and Th0 cells decreased the expression of IL-2, TNF-alpha, and IFN-gamma. Several chemokines, including Th2 chemokines CCL17 and CCL22, were up-regulated by SPHK1 short interfering RNA and down-regulated by overexpression of SPHK1. We also showed that Th2 cells themselves express CCL17 and CCL22. Finally, we conclude that SPHK1 negatively regulates the inflammatory responses of Th1 cells by inhibiting the production of proinflammatory cytokines and chemokines.

Animals↗

PubMed2005

A new congenital nuclear cataract caused by a missense mutation in the gammaD-crystallin gene (CRYGD) in a Chinese family.

PURPOSE: To identify genetic defects associated with nuclear golden crystal autosomal dominant congenital cataract (ADCC) in a Chinese pedigree in the north of China. METHODS: Clinical data were collected and the phenotype of the affected members in this family was recorded by slit lamp photography. Genomic DNA was isolated from peripheral blood. Linkage analyses excluded all known loci except that in 2q33-q35. Mutation analysis of CRYGs was carried by direct sequencing of the PCR products. RESULTS: Sequencing of the coding regions of CRYGA, CRYGB, CRYGC, and CRYGD showed the presence of a heterozygous C>A transversion at nt109 of the coding sequence (R36S) in exon 2 of CRYGD, which co-segregated with the affected members. CONCLUSIONS: The R36S mutation in CRYGD identified in this Chinese family caused a nuclear golden crystal cataract phenotype not described before. This finding is an additional indication that there may be phenotypic heterogeneity of cataract, especially in different races.

Asian People↗

PubMed2005

Heterologous production of daptomycin in Streptomyces lividans.

Daptomycin and the A21978C antibiotic complex are lipopeptides produced by Streptomyces roseosporus and also in recombinant Streptomyces lividans TK23 and TK64 strains, when a 128 kbp region of cloned S. roseosporus DNA containing the daptomycin gene cluster is inserted site-specifically in the phiC31 attB site. A21978C fermentation yields were initially much lower in S. lividans than in S. roseosporus, and detection was complicated by the production of host metabolites. However A21978C production in S. lividans was improved by deletion of genes encoding the production of actinorhodin and by medium optimization to control the chemical form of the calcium dependent antibiotic (CDA). This latter compound has not previously been chemically characterized as a S. lividans product. Adding phosphate to a defined fermentation medium resulted in formation of only the phosphorylated forms of CDA, which were well separated from A21978C on chromatographic analysis. Adjusting the level of phosphate in the medium led to an improvement in A21978C yield from 20 to 55 mg/l.

Anthraquinones↗

PubMed2005

Metagenomics-based drug discovery and marine microbial diversity.

As the global threat of drug-resistant pathogens continues to rise, new strategies and resources are required to accelerate and advance the drug discovery process. We believe that rapid progress in metagenomics has opened up a new era in the study of marine microbial diversity that enables direct access to the genomes of numerous uncultivable microorganisms. This review outlines recent developments and future trends in metagenomics-based drug discovery in marine microbial communities and their associated chemical prosperity.

Chromosome Mapping↗

PubMed2005

[The protective effects of three components isolated from Astragalus membranaceus on shock wave lithotripsy induced kidney injury in rabbit model].

OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) is has been shown to reduce renal parenchymal injury subject to application of shock wave lithotripsy in our pervious study. To investigate the protective action of three main components from Astragalus membranaceus, including total saponins of astragalus (TSA), total flavonoids of astragalus (TFA) total polysaccharide of astragalus (TPA) in alleviating shock wave induced kidney damage. METHODS: Sixty four male rabbits were randomly assigned to a control group or to 3 groups that were premedicated with TSA TFA and TPA respectively prior to application of ESWL. Each group of animals underwent shock wave lithotripsy (18 kV) to the right kidneys and received a total of 1500 shocks. Peripheral blood samples were collected to evaluate the levels of plasma endothelin-1 (ET-1), plasma nitric oxide (NO) and serum malondialdehyde (MDA) before and after shock wave treatment. The concentrations of these markers in the treated kidney tissues were also detected 3 days, 7 days and 14 days after application of ESWL. The changes of histopathology and cells ultrastructure were observed through light microscope and electron microscope. Untreated contralateral kidneys were evaluated as controls. RESULTS: In control serials the levels of ET-1 and MDA were elevated significantly while the level of NO was significantly decreased after application of shock wave lithotripsy (P < 0.05). The comparison between the controls and premedicated groups demonstrated that all these three components especially TSA and TFA significantly inhibited shock wave induced increasing of ET-1 and MDA (P < 0.05). TSA also significantly suppressed the decrease of NO and made the recovery time earlier compare to the results of controls (P < 0.05). However, TFA and TPA had almost no effects on the change of NO. (P > 0.05). The results in histopathology showed noticeably damage of glomerular and tubular epithelial cells in the treated kidneys in the controls. The histological alterations in the TPA group were similar to those of the controls. These alterations were significantly milder in the TSA and TFA particular the TSA group. CONCLUSION: TFA and TSA, especially TSA seemed to play the key role in alleviating ESWL induced kidney damage.

Animals↗

PubMed2005

PBT-3, a hepoxilin stable analog, causes long term inhibition of growth of K562 solid tumours in vivo.

We demonstrate herein that daily administration of PBT-3 for 8 days to NU/NU mice bearing solid tumours derived from the s.c. administration of the leukemic cell line K562 results in inhibition of growth of the tumours in vivo, and this inhibition lasts for 60 days after stopping treatment with PBT-3 before recovery of tumour growth is re-established. Similar findings were observed when the mice were treated with Gleevec (STI-571). These results provide new evidence that PBT-3 is effective in controlling solid tumour growth in vivo and suggest that the PBT family may be useful in the development of new drugs in cancer therapy.

8,11,14-Eicosatrienoic Acid↗

PubMed2005

Formation of polysulfone colloids for adsorption of natural organic foulants.

An ever-present problem in the use of commercial membranes for treatment of drinking water is fouling of the membranes by natural organic matter (NOM). This work describes a new approach to elimination or minimization of membrane fouling by NOM. When a 2% solution of polysulfone in NMP and propionic acid is slowly injected into water, approximately 50 nm polysulfone particles are spontaneously formed, and these hydrophobic particles quickly coagulate into approximately 12-microm diameter aggregates; the formed material has a surface area of approximately 100 m(2)/g and an equivalent "pore" size of 25 nm. When 50 mg/L of the new material is equilibrated with a local drinking water supply, virtually all adsorptive fouling of a 20-kDa molecular weight cutoff ultrafiltration membrane is eliminated. Interestingly, although only a very small percentage of the NOM is removed by adsorption on the polysulfone aggregates, it appears that exactly this small NOM component is responsible for nearly all of the membrane fouling. This paper describes the fabrication and characterization of the new polysulfone adsorbent and offers an hypothesis for the formation of the product via spontaneous emulsification and spinodal decomposition.

Journal Article↗

PubMed2005

RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells.

PDE4B and PDE4D provide >90% of PDE4 cAMP phosphodiesterase activity in human embryonic kidney (HEK293B2) cells. Their selective small interference RNA (siRNA)-mediated knockdown potentiates isoprenaline-stimulated protein kinase A (PKA) activation. Whereas endogenous PDE4D co-immunoprecipitates with beta arrestin, endogenous PDE4B does not, even upon PDE4D knockdown. Ectopic overexpression of PDE4B2 confers co-immunoprecipitation with beta arrestin. Knockdown of PDE4D, but not PDE4B, amplifies isoprenaline-stimulated phosphorylation of the beta2-adrenergic receptor (beta2-AR) by PKA and activation of extracellular signal-regulated kinase (ERK) through G(i). Isoform-selective knockdown identifies PDE4D5 as the functionally important species regulating isoprenaline stimulation of both these processes. Ht31-mediated disruption of the tethering of PKA to AKAP scaffold proteins attenuates isoprenaline activation of ERK, even upon PDE4D knockdown. Selective siRNA-mediated knockdown identifies AKAP79, which is constitutively associated with the beta2-AR, rather than isoprenaline-recruited gravin, as being the functionally relevant AKAP in this process. Isoprenaline-stimulated membrane recruitment of PDE4D is ablated upon beta arrestin knockdown. A mutation that compromises interactions with beta arrestin prevents catalytically inactive PDE4D5 from performing a dominant negative role in potentiating isoprenaline-stimulated ERK activation. Beta arrestin-recruited PDE4D5 desensitizes isoprenaline-stimulated PKA phosphorylation of the beta2-AR and the consequential switching of its signaling to ERK. The ability to observe a cellular phenotype upon PDE4D5 knockdown demonstrates that other PDE4 isoforms, expressed at endogenous levels, are unable to afford rescue in HEK293B2 cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Geometric cooperativity and anticooperativity of three-body interactions in native proteins.

Characterizing multibody interactions of hydrophobic, polar, and ionizable residues in protein is important for understanding the stability of protein structures. We introduce a geometric model for quantifying 3-body interactions in native proteins. With this model, empirical propensity values for many types of 3-body interactions can be reliably estimated from a database of native protein structures, despite the overwhelming presence of pairwise contacts. In addition, we define a nonadditive coefficient that characterizes cooperativity and anticooperativity of residue interactions in native proteins by measuring the deviation of 3-body interactions from 3 independent pairwise interactions. It compares the 3-body propensity value from what would be expected if only pairwise interactions were considered, and highlights the distinction of propensity and cooperativity of 3-body interaction. Based on the geometric model, and what can be inferred from statistical analysis of such a model, we find that hydrophobic interactions and hydrogen-bonding interactions make nonadditive contributions to protein stability, but the nonadditive nature depends on whether such interactions are located in the protein interior or on the protein surface. When located in the interior, many hydrophobic interactions such as those involving alkyl residues are anticooperative. Salt-bridge and regular hydrogen-bonding interactions, such as those involving ionizable residues and polar residues, are cooperative. When located on the protein surface, these salt-bridge and regular hydrogen-bonding interactions are anticooperative, and hydrophobic interactions involving alkyl residues become cooperative. We show with examples that incorporating 3-body interactions improves discrimination of protein native structures against decoy conformations. In addition, analysis of cooperative 3-body interaction may reveal spatial motifs that can suggest specific protein functions.

Computer Simulation↗

PubMed2005

Enantioselective recognition of carboxylates: a receptor derived from alpha-aminoxy acids functions as a chiral shift reagent for carboxylic acids.

Enantioselective recognition of carboxylates has important implications in asymmetric synthesis and drug discovery. We have prepared a novel C2-symmetric receptor 1 from alpha-aminoxy acids in a high overall yield. A series of chiral recognition studies indicate that receptor 1 not only can bind to carboxylate ions tightly but also has a good ability to recognize enantiomers of a broad variety of carboxylic acids in the 1H NMR spectra. Thus, the receptor 1 can be used as a chiral shift reagent for the determination of enantiomeric purities of chiral carboxylic acids by 1H NMR directly and rapidly.

Amino Acids↗

PubMed2005

A cyclic hexapeptide comprising alternating alpha-aminoxy and alpha-amino acids is a selective chloride ion receptor.

In nonpolar solvents, the cyclic hexapeptide 2, which comprises alternating D-alpha-amino and D-alpha-aminoxy acids, adopts a C3-symmetric conformation with alternating eight (N--O turns)- and seven (gamma turns)-membered-ring hydrogen bonds. A series of anion-binding studies has suggested that 2 can function as an effective anion receptor that not only displays a high selectivity for chloride ions, but also the capability to extract chloride ions from aqueous solutions into organic phases.

Amination↗

PubMed2005

Where to locate the isocenter? The treatment strategy for repeat trigeminal neuralgia radiosurgery.

PURPOSE: The purpose of this study is to investigate how the spatial relationship between the isocenters of the first and second radiosurgeries affects the overall outcome. METHODS AND MATERIALS: We performed a retrospective study on 40 patients who had repeat gamma knife radiosurgery for trigeminal neuralgia. Only one 4-mm isocenter was applied in both first and second radiosurgeries, with a maximum radiation dose of 75 Gy and 40 Gy, respectively. The MR scan of the first radiosurgery was registered to that of the second radiosurgery by a landmark-based registration algorithm. The spatial relationship between the isocenter of the first and the second radiosurgeries was thus determined. The investigating parameters were the distance between the isocenters of the two separate radiosurgeries and isocenter proximity to the brainstem. The outcome end points were pain relief and dysesthesias. The median follow-up for the repeat radiosurgery was 28 months (range, 6-51 months). RESULTS: Pain relief was complete in 11 patients, nearly complete (> or =90%) in 7 patients, partial (> or =50%) in 8 patients, and minimal (<50%) or none in another 14 patients. The mean distance between the two isocenters was 2.86 mm in the complete or nearly complete pain relief group vs. 1.93 mm in the others. Farther distance between isocenters was associated with a trend toward better pain relief (p = 0.057). The proximity of the second isocenter to the brainstem did not affect pain relief, and neither did placing the second isocenter proximal or distal to the brainstem compared with the first one. Three patients developed moderate dysesthesias (score of 4 on a 0-10 scale), and 2 other patients developed more significant dysesthesias (score of 7) after the second radiosurgery. Dysesthesias related neither to distance between isocenters nor to which isocenter was closer to the brainstem. CONCLUSIONS: Image registration between MR scans of the first and second radiosurgeries helps target delineation and radiosurgery treatment planning. Increasing the isocenter distance between the two radiosurgeries treated a longer segment of the trigeminal neuralgia nerve and was associated with a trend toward improved pain relief.

Adult↗

PubMed2005

G protein beta2 subunit-derived peptides for inhibition and induction of G protein pathways. Examination of voltage-gated Ca2+ and G protein inwardly rectifying K+ channels.

Voltage-gated Ca2+ channels of the N-, P/Q-, and R-type and G protein inwardly rectifying K+ channels (GIRK) are modulated via direct binding of G proteins. The modulation is mediated by G protein betagamma subunits. By using electrophysiological recordings and fluorescence resonance energy transfer, we characterized the modulatory domains of the G protein beta subunit on the recombinant P/Q-type channel and GIRK channel expressed in HEK293 cells and on native non-L-type Ca2+ currents of cultured hippocampal neurons. We found that Gbeta2 subunit-derived deletion constructs and synthesized peptides can either induce or inhibit G protein modulation of the examined ion channels. In particular, the 25-amino acid peptide derived from the Gbeta2 N terminus inhibits G protein modulation, whereas a 35-amino acid peptide derived from the Gbeta2 C terminus induced modulation of voltage-gated Ca2+ channels and GIRK channels. Fluorescence resonance energy transfer (FRET) analysis of the live action of these peptides revealed that the 25-amino acid peptide diminished the FRET signal between G protein beta2gamma3 subunits, indicating a reorientation between G protein beta2gamma3 subunits in the presence of the peptide. In contrast, the 35-amino acid peptide increased the FRET signal between GIRK1,2 channel subunits, similarly to the Gbetagamma-mediated FRET increase observed for this GIRK subunit combination. Circular dichroism spectra of the synthesized peptides suggest that the 25-amino acid peptide is structured. These results indicate that individual G protein beta subunit domains can act as independent, separate modulatory domains to either induce or inhibit G protein modulation for several effector proteins.

Amino Acid Sequence↗

PubMed2005

On the interaction of electrons with betaine zwitterions.

Betaine is a permanent zwitterion. The molecular betaine anion has been generated in a hybrid, infrared desorption-electron photoemission source and its photoelectron spectrum recorded. The photoelectron spectrum of the betaine anion is characteristic of a dipole bound anion, and its vertical detachment energy was measured to be 0.29+/-0.03 eV. Calculations by Rak, Skurski, and Gutowski [J. Chem. Phys. 114, 10673 (2001)] had found the betaine anion to be a dipole bound anion with a vertical detachment energy of 0.28 eV. We also measured the vertical detachment energy of deprotonated betaine to be approximately 1.9 eV.

Journal Article↗