Biomedical subjects

Li Li

Publications and source records attributed to Li Li.

At least 91 records · Page 5Linked to original sources

PubMed2006

PDGF-C participates in branchial arch morphogenesis and is down-regulated by retinoic acid.

Retinoic acid (RA) is a teratogen that induces a variety of craniofacial abnormalities, including branchial arch deformities and cleft palate. Platelet-derived growth factor C (PDGF-C) is a recently identified member of the PDGF family. PDGF-C contributes to normal development of the heart, central nervous system, kidney and palatogenesis. But the roles of PDGF-C in branchial arches development and the relationship between PDGF-C and RA-induced branchial arches abnormalities are poorly understood. We examined the effects of RA on PDGF-C and its receptor PDGFR-alpha expressions. We demonstrated that administration of RA to mouse embryos resulted in dramatic losses of PDGF-C and its receptor PDGFR-alpha. Furthermore, we confirmed that blocking PDGF-C signaling by anti-PDGF-C neutralization antibody led to branchial arch malformations similar to that of RA induced, both hypoplastic branchial arches and FBA. These findings suggest the down-regulation of PDGF-C may be one of mechanisms of branchial arch abnormalities induced by RA and PDGF-C signaling is required for branchial arch morphogenesis.

Animals↗

PubMed2006

Dynamic changes in chromatin acetylation and the expression of histone acetyltransferases and histone deacetylases regulate the SM22alpha transcription in response to Smad3-mediated TGFbeta1 signaling.

TGFbeta1 plays critical roles in stimulating smooth muscle gene transcription during myofibroblast and smooth muscle cell (SMC) differentiation. Increasing evidence demonstrates that histone modification plays important roles in regulating gene transcription. Here, we investigated the effect of changes in the expression of histone acetyltransferases (HAT) or histone deacetylases (HDAC) on TGFbeta1-induced SM22 promoter activities. We found that overexpressing HAT proteins such as p300 and CBP enhances TGFbeta1-induced SM22 promoter activities; conversely, overexpressing HAT inhibitor such as Twist1 (but not Twist2/Dermo-1) and E1A suppresses this effect of TGFbeta1. We also found that TSA, a HDAC inhibitor that stimulates histone acetylation of the SM22alpha locus, further enhances the transactivational activity of Smad2, Smad3 and Smad4, and relieves the inhibitory effect of Smad6, Smad7, and the dominant negative mutants of Smads. TGFbeta1 also stimulates the association of Smad3 (a potent transactivator for the SM22 promoter) and p300 by co-immunoprecipitation assay. In contrast, overexpressing HDAC 1-6 inhibits TGFbeta1-induced as well as Smad3 and myocardin-activated SM22 promoter. Moreover, chromatin immunoprecipitation (ChIP) assays show that TGFbeta1 induces histone acetylation at the SM22alpha locus. This study demonstrates that the balance of HAT and HDAC expression affects TGFbeta1-induced SM22alpha transcription; TGFbeta1-induced SM22alpha transcription is accompanied by histone hyperacetylation at the SM22alpha locus. This study provides the first evidence showing that histone hyperacetylation of the SM22 promoter is a target of TGFbeta1 signaling, suggesting that modulation of histone acetylation is involved in the molecular mechanisms of TGFbeta1-regulated SMC gene transcription.

Acetylation↗

PubMed2006

A brassinolide-suppressed rice MADS-box transcription factor, OsMDP1, has a negative regulatory role in BR signaling.

The MADS-box transcription factor-encoding genes are expressed mainly during plant reproductive development, where they play important roles in controlling floral organ initiation and identity. Few previous reports have investigated the functions of MADS-box transcription factors expressed in vegetative tissues. Here we describe the functional characterization of a rice AG-like MADS-box protein, OsMDP1 (Oryza sativa MADS-domain-containing protein 1). A partial cDNA encoding a MADS-box domain was identified via high-throughput screening of rice brassinolide-regulated genes, and the full-length cDNA was subsequently isolated via screening of a cDNA library constructed from rice materials at tillering stage. Expression pattern analyses indicated that OsMDP1 is transcribed mainly in vegetative tissues, including the mature leaf, coleoptile, root-elongation zone, culm internode, and especially the joint region between the leaf blade and sheath. Further studies revealed that transcription of OsMDP1 is stimulated by darkness and suppressed by brassinolide treatment. OsMDP1 deficiency resulted in shortened primary roots, elongated coleoptiles and enhanced lamina joint inclinations. Moreover, transgenic plants showed hypersensitivities to exogenous brassinolide in terms of lamina joint inclination and coleoptile elongation. OsMDP1 deficiency resulted in enhanced expression of OsXTR1, which encodes xyloglucan endotransglycosylase, the cell-wall loosening enzyme necessary for cell elongation, and modulated expressions of multiple genes involved in cell signalling and gene transcription, indicating the key negative regulatory role of OsMDP1 in BR signalling.

Amino Acid Sequence↗

PubMed2006

Stimulant use and symptoms of abuse/dependence: epidemiology and associations with cannabis use--a twin study.

BACKGROUND: This paper explores the magnitude of--and extent of overlap between--additive genetic, shared environmental and non-shared environmental influences on lifetime stimulant use and on stimulant abuse/dependence symptoms; the associations between stimulant use and cannabis use and the extent to which these associations can be attributed to common or correlated genetic and environmental influences. METHODS: Self-report data on lifetime stimulant use, abuse/dependence symptoms and corresponding measures of cannabis involvement were collected from a sample of 6265 male and female Australian twins born 1964-1971. RESULTS: Approximately one in five study participants reported lifetime stimulant use while 5% reported experiencing at least one symptom of abuse/dependence. Multivariate genetic model fitting indicated moderate genetic influences on stimulant use (40%) and symptoms (65%) while there was no evidence of sex differences in the magnitude of these influences. Despite some overlap in genetic influences on these measures, approximately 60% of the genetic variance in symptoms was specific to this phenotype. There were also strong genetic and shared environmental correlations between the factors associated with stimulant use and those associated with cannabis use. CONCLUSIONS: There were moderate genetic influences on stimulant use and stimulant abuse/dependence with moderate overlap between the genetic factors associated with these outcomes. Additionally, there were strong associations between measures of lifetime stimulant use and analogous measures of cannabis use which, importantly, could be largely attributed to shared familial risk factors predisposing to both stimulant and cannabis use.

Adult↗

PubMed2006

A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus.

Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop.

Animals↗

PubMed2006

Elevated hepatic SULT1E1 activity in mouse models of cystic fibrosis alters the regulation of estrogen responsive proteins.

BACKGROUND: Previous studies with cystic fibrosis transmembrane conductance regulator (CFTR) DeltaF508 mice indicate that estrogen levels may play a role in the occurrence or severity of CF-associated liver disease. However, the underlying mechanisms of liver disease in CF are poorly understood. METHODS: The levels of SULT1E1 (estrogen sulfotransferase) were measured in livers of control and CFTR-knockout (KO) mice. The impact of increased SULT1E1 activity on hepatic protein expression was assessed by immunoblot and MALDI mass spectrometric analysis. RESULTS: SULT1E1 expression was significantly elevated in livers of several CFTR-KO mice. SULT1E1 and CFTR were specifically detected in hepatocytes and cholangiocytes, respectively. Elevated SULT1E1 activity may result in lower levels of free beta-estradiol thereby altering estrogen-responsive hepatic protein expression. Estrogen receptors (ER)-alpha and beta were differentially regulated in CFTR-KO and CFTR-DeltaF508 mice. ERalpha expression was reduced in mice with high SULT1E1 activity. Glutathione S-transferase-P1 and carbonic anhydrase III were significantly decreased in CFTR (-/-) mice with high SULT1E1 activity. Furthermore, cytochrome P450 2B9, also estrogen regulated, was significantly induced in the livers of CFTR (-/-) mice with high SULT1E1 activity. CONCLUSIONS: Elevated SULT1E1 levels and associated alterations in estrogen-regulated hepatic protein expression may play an important role in CF liver disease.

Animals↗

PubMed2006

PPARalpha-mediated upregulation of uncoupling protein-2 switches cyanide-induced apoptosis to necrosis in primary cortical cells.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear factor PPAR family that regulates a variety of cellular functions, including lipid metabolism, cellular oxidative stress defense, and inflammatory responses. Based on the report that Wy14,643, a PPARalpha agonist, can upregulate uncoupling protein-2 (UCP-2), this study was conducted in primary cortical cells to determine if PPARalpha activation enhances cyanide-induced neurotoxicity through changes in the level of UCP-2. PCR and Western blot analysis showed that Wy14,643 upregulated UCP-2 transcriptionally over a 12-h period. This response was mediated by PPARalpha since it was blocked by MK886, a selective PPARalpha antagonist. The effect of UCP-2 upregulation on the cytotoxic response to cyanide was quantitated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (apoptosis) and propidium iodide staining (necrosis). Wy14,643 switched the mode of cyanide-induced cell death from apoptosis to necrosis. Cell death was preceded by marked mitochondrial dysfunction, as reflected by depletion of ATP and reduction of the mitochondrial membrane potential (DeltaPsim). Knock down of UCP-2 expression by RNA interference blocked the Wy14,643-mediated enhancement of cyanide-induced mitochondrial dysfunction and the switch of the cell death mode, thus confirming that the response was mediated by upregulation of UCP-2. This study shows that PPARalpha activation can upregulate UCP-2 expression, which in turn enhances cyanide-induced necrotic cell death through an increase of mitochondrial dysfunction.

Animals↗

PubMed2006

Characterization of a flocculation-like phenotype in Cryptococcus neoformans and its effects on pathogenesis.

We investigated the phenomenon of cell-cell aggregation (flocculation) in a serotype D strain of Cryptococcus neoformans (ATCC 24067, isolate RC-2). Cell aggregation into clumps of 5-40 cells (clump+ cells) occurred during the early log phase and disappeared in the beginning of the stationary phase (clump- cells). The cell aggregation phenomenon was medium dependent. Clump+ cells could be dispersed by either vortexing or proteinase K digestion. Most importantly, the transient change in cellular phenotype changed several important host-pathogen interactions. Adherence of clump+ cells to murine macrophage-like cells J774.16 was significantly (P < 0.001) enhanced compared with adherence of clump- cells. Furthermore, complement-mediated phagocytosis efficacy of dispersed clump+ cells was significantly higher (P < 0.001) compared with clump- cells. Similar findings were documented with an in vivo phagocytosis assay. Infection of mice with a low inoculum (10(4)) of clump+ cells resulted in lower fungal burden when compared with mice infected with clump- cells. Accordingly, mice infected with clump+ cells survived significantly longer than mice infected with clump- cells. These results indicate that the cellular phenotype undergoes significant changes that result in a transient flocculation-like phenotype. We hypothesize that this cell-cell aggregation is the result of changes in protein content in the polysaccharide capsule. We conclude from our data that the change in cellular phenotype has a dramatic effect on cell adherence, and on complement-mediated phagocytosis, both of which can affect the pathogenesis of the disease in the host. Our results underscore the complexity of studies that investigate host pathogen interactions and may explain differences and inconsistencies observed in in vitro and in vivo assays.

Animals↗

PubMed2006

Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP-kinase.

Policosanol is a mixture of long-chain primary alcohols that has been shown to decrease serum cholesterol in animals and in humans. The hypocholesterolemic effect results from a decrease in cholesterol synthesis by suppression of HMG-CoA reductase activity, but the mechanism of this suppression and the active components of policosanol have not been established. In the present study, we investigated the ability of policosanol and its principal components to inhibit cholesterol synthesis in cultured rat hepatoma cells. Maximal inhibition by policosanol yielded a 30% decrease in [(14)C]acetate incorporation without evidence of cellular toxicity. Octacosanol (C28, the major constituent of policosanol), heptacosanol (C27), and hexacosanol (C26) yielded smaller and statistically insignificant decreases in cholesterol synthesis, whereas triacontanol (1-hydroxytriacontane; C30) replicated the inhibition obtained with policosanol. At pharmacological concentrations (<5 microg/ml), policosanol and triacontanol decreased [(14)C]acetate incorporation into cholesterol without affecting the incorporation of [(14)C]mevalonate, indicating that these compounds act at or above HMG-CoA reductase. Policosanol and triacontanol did not directly inhibit HMG-CoA reductase, and incubation of these compounds with hepatoma cells did not affect reductase enzyme levels. However, reductase activity was decreased by up to 55% in lysates prepared from these cells, suggesting that HMG-CoA reductase activity was down-regulated by policosanol treatment. Consistent with this hypothesis, a 3-fold increase in AMP-kinase phosphorylation was noted in policosanol-treated cells. Because AMP-kinase is activated by phosphorylation and is well established to suppress HMG-CoA reductase activity, these results suggest that policosanol or a metabolite decreases HMG-CoA reductase activity by activating AMP-kinase.

Adenylate Kinase↗

PubMed2006

(Glycylglycinato-kappa3O,N,N')(2-methyl-1H-benzimidazole-kappaN3)copper(II) trihydrate.

In the title compound, [Cu(C4H6N2O3)(C8H8N2)].3H2O, the Cu(II) atom is coordinated in a square-planar manner by one O atom and three N atoms from glycylglycinate and 2-methylbenzimidazole ligands. The ternary complexes assemble into one-dimensional chains through C-H...pi interactions and direct N-H...O hydrogen bonding, as well as into hydrogen-bonded water helices with branches which also link the complex chains into a three-dimensional supramolecular structure.

Carbon↗

PubMed2006

The Na2 2 3pi(g) state: new observations and hyperfine structure.

Many more Na2 2 3pi(g) v = 0-43, omega = 0, 1, 2 levels have been observed by sub-Doppler continuous wave perturbation facilitated optical-optical double resonance fluorescence excitation spectroscopy and the hyperfine structure of the omega = 0 and 2 levels has been resolved. New molecular constants for the less perturbed v = 0-43 levels have been obtained with these new and the previously reported data. The hyperfine coupling scheme of the observed 2 3pi(g) levels is close to Hund's case a(beta) with a Fermi contact constant b(F) = 160+/-5 MHz, which is smaller than the Fermi contact constants of other Na2 triplet Rydberg states, b(F) = 200-245 MHz.

Journal Article↗

PubMed2006

A novel preparation of three-dimensionally ordered macroporous M/Ti (M=Zr or Ta) mixed oxide nanoparticles with enhanced photocatalytic activity.

Three-dimensionally ordered macroporous (3 DOM) M/Ti (M=Zr or Ta) mixed oxides were prepared by cohydrolysis of a mixture of Zr(n-OC(4)H(9))(4)/TTIP or TaCl(5)/TTIP (TTIP=titanium isopropoxide) combined with a polystyrene (PS) latex sphere templating technique. The resulting products exhibited homogeneous wall compositions, namely, Zr or Ta was uniformly dispersed into the TiO(2) framework with the loading levels of 5, 10, and 20 mol% for Zr and 2.5, 5.0, and 7.5 mol% for Ta, respectively. The estimated macropore diameter, wall thickness, and particle size of the products ranged from 280 to 290 nm, from 30 to 50 nm, and from 10 to 12 nm, respectively. The products showed only anatase phase structure although their starting solitary metal oxides exhibited suitable crystalline structures under the same preparation conditions. Raman scattering spectroscopy showed that the crystal structure of titania had a slight interference due to the incorporation of Zr or Ta, and UV-vis diffuse reflectance spectroscopy (DRS) showed the narrower band gap of the products compared with that of pure anatase TiO(2). The products exhibited mesoporous wall structures, and their BET surface areas were higher than those of the corresponding pure 3 DOM metal oxides. The UV-light photocatalytic activity of the products was assessed by monitoring the photodegradation of two organic molecules including 4-nitrophenol (4-NP) and rhodamine B (RB). Both the photocatalytic reactions confirmed that the presence of the second metal oxide in the titania framework resulted in enhanced photocatalytic activity compared with the pure titania framework.

Journal Article↗

PubMed2006

New cytochrome P450 2D6*56 allele identified by genotype/phenotype analysis of cryopreserved human hepatocytes.

Genotype/phenotype analysis with human hepatocytes has identified a new inactive CYP2D6 allele, CYP2D6*56. Cryopreserved human hepatocytes from 51 livers were evaluated for CYP2D6 activity with dextromethorphan as the probe substrate. Hepatocyte lots that lacked CYP2D6 activity were further evaluated for CYP2D6 expression and known genetic variations, including CYP2D6*2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *14, *15, *17, *18, *19, *20, *25, *26, *29, *30, *35, *40, *41, *43, and various multiple copy CYP2D6 alleles (*1xn, *2xn, and *4xn) by the AmpliChip CYP450 prototype microarray (Roche Molecular Systems, Inc., Branchburg, NJ). Two discrepancies were uncovered between the CYP2D6 genotype and activity by this approach. In one sample, a previously unreported 3201C 224 T transition in exon 7 resulted in Arg344(CGA) being replaced by a stop codon (TGA), resulting in a CYP2D6 enzyme lacking the terminal 153 amino acids. This allele was given the designation of CYP2D6*56 and the GenBank accession number DQ282162. The lack of CYP2D6 activity in cryopreserved hepatocytes and microsomes found in the second sample, despite a normal level of CYP2D6 expression and a genotype (*10/*1) predictive of normal CYP2D6 activity, was attributed to enzyme inactivation by an unknown metabolite. The identification and characterization of the CYP2D6*56 allele indicates that commercial cryopreserved human hepatocytes may provide a valuable means to rapidly identify genetic variations with functional relevance. This integrated approach of identifying alleles and examining allele relationships to gene expression and function could be of tremendous value to understanding the mechanism responsible for functional differences in gene variation. The commercial availability of human cryopreserved hepatocytes also makes this potential readily available to any who are interested in it, not just those with access to private liver banks.

Alleles↗

PubMed2006

Inferring functional linkages between proteins from evolutionary scenarios.

Identifying potential protein interactions is of great importance in understanding the topologies of cellular networks, which is much needed and valued in current systematic biological studies. The development of our computational methods to predict protein-protein interactions have been spurred on by the massive sequencing efforts of the genomic revolution. Among these methods is phylogenetic profiling, which assumes that proteins under similar evolutionary pressures with similar phylogenetic profiles might be functionally related. Here, we introduce a method for inferring functional linkages between proteins from their evolutionary scenarios. The term evolutionary scenario refers to a series of events that occurred in speciation over time, which can be reconstructed given a phylogenetic profile and a species tree. Common evolutionary pressures on two proteins can then be inferred by comparing their evolutionary scenarios, which is a direct indication of their functional linkage. This scenario method has proven to have better performance compared with the classical phylogenetic profile method, when applied to the same test set. In addition, predicted results of the two methods are found to be fairly different, suggesting the possibility of merging them in order to achieve a better performance. We analyzed the influence of the topology of the phylogenetic tree on the performance of this method, and found it to be robust to perturbations in the topology of the tree. However, if a completely random tree is incorporated, performance will decline significantly. The evolutionary scenario method was used for inferring functional linkages in 67 species, and 40,006 linkages were predicted. We examine our prediction for budding yeast and find that almost all predicted linkages are supported by further evidence.

Computational Biology↗

PubMed2006

Adenovirus-mediated intra-tumoral delivery of the human endostatin gene inhibits tumor growth in nasopharyngeal carcinoma.

The growth and metastasis of nasopharyngeal carcinoma (NPC), one of the most common cancers in southern China, is closely related to neovascularization. Here, we examined whether intra-tumoral delivery of endostatin gene could lead to long-term local expression of bioactive endostatin at therapeutic levels. We constructed a recombinant adenoviral vector carrying the human endostatin gene (Ad/hEndo), which expressed high-level endostatin protein in NPC CNE-2 cells, and significantly inhibited the proliferation and migration of vascular endothelial cells in vitro. Tumor growth and angiogenesis in NPC CNE-2 xenografted tumors were significantly inhibited after 5 courses of intra-tumoral treatment with Ad/hEndo in vivo. Endostatin mRNA in tumor tissues peaked at 1-2 days after intra-tumoral administration and disappeared within 1 week, whereas the plasma endostatin protein levels peaked at 3 days after administration and lasted 2-3 weeks. The therapeutically relevant endostatin transgene expression was achieved during the course of multiple intra-tumoral administrations with Ad/hEndo. Multiple injections with adenoviral vectors did not lead to continuous increases of adenovirus neutralizing antibodies in serum. Thus, adenovirus-mediated intra-tumoral introduction of the human endostatin gene may form a viable new treatment for NPC, although readministration every 2-3 weeks may be necessary for the best effect.

Adenoviridae↗

PubMed2006

trans-Dichlorotetrabenzimidazolecadmium(II) tetrabenzimidazole: a three-dimensional supramolecular structure built from C-H...pi, N-H...Cl and N-H...N hydrogen bonds.

The title compound, [CdCl2(C7H6N2)4].4C7H6N2, consists of a Cd(Bzim)4Cl2 complex (Bzim is benzimidazole) lying on a fourfold rotation axis in the space group P4nc, and four benzimidazole molecules which are linked to the coordinated benzimidazole unit by N-H...N hydrogen bonds. One N-H...Cl and three C-H...pi hydrogen bonds link these units into a three-dimensional supramolecular structure.

Benzimidazoles↗

PubMed2006

Fabrication of UV-blocking nanohybrid coating via miniemulsion polymerization.

A novel convenient approach to fabricate ZnO@polystyrene nanohybrid coating on cotton fabrics is reported. The as-prepared core-shell nanohybrid coating was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), energy dispersive X-ray (EDX), and UV-blocking. The cotton fabrics treated in this study provided ultrahigh UV protection and superior wash fastness. Therefore, this new nanohybrid material and its synthesis method are highly potential to various functional treatments of flexible surfaces.

Journal Article↗

PubMed2006

Polymorphisms in estrogen bioactivation, detoxification and oxidative DNA base excision repair genes and prostate cancer risk.

To date, the potential impact of hormones on prostate cancer has predominantly focused on receptor-mediated events. However, catechol estrogens, if not inactivated by catechol-O-methyltransferase (COMT), can generate large quantities of reactive oxygen species (ROS). ROS may cause a spectrum of damage including oxidative DNA base lesions, which can lead to irreversible mutation(s) if they are not repaired by base excision repair (BER) systems. hOGG1 is a key enzyme in short patch BER because it recognizes and performs initial excision of the most common form of oxidative DNA base damage, 8-hydroxyguanine (8-oxo-dG). To investigate potential non-receptor-mediated estrogen effects, we evaluated the association between COMT Val158Met and hOGG1 Ser326Cys polymorphisms and prostate cancer in a family-based case-control study (439 prostate cancer cases, 479 brother controls). We observed no noteworthy associations between these polymorphisms and prostate cancer risk in the total study population. However, among men with more aggressive prostate cancer, the hOGG1 326 Cys/Cys genotype was inversely associated with disease (OR=0.30; 95% CI=0.09-0.98). Combining the lower activity CYP1B1 432 Leu/Leu or Leu/Val genotypes (which may decrease the level of catechol estrogens and ROS generated) with the hOGG1 326 Cys/Cys genotype and the XRCC1 399 Arg/Arg or Arg/Gln genotypes (which may enhance BER) resulted in an even further reduced risk in Caucasians with more aggressive disease (OR=0.09; 95% CI=0.01-0.56). Including the high-activity COMT 158Val allele to this combination also lowered aggressive prostate cancer risk but the effect was not as strong (OR=0.20; 95% CI=0.05-0.88). The decreased risk we observed with the hOGG1 326 Cys/Cys genotype confirms an earlier report and the further reduced risk found with the CYP1B1 (432 Leu/Leu or Leu/Val)-hOGG1 (326 Cys/Cys)-XRCC1 (Arg/Arg or Arg/Gln) genotype combination may lend new insights to the importance of ROS generated from non-receptor-mediated estrogenic mechanisms in more aggressive prostate cancer.

Aged↗