In Vitro Production of TNF-alpha,IL-6 and SIL-2R in Chinese Patients with Ulcerative Colitis

World Journal of Gastroenterology : WJG. Jun, 1998  |  Pubmed ID: 11819289

AIM:To determine the tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and soluble interleukin 2 receptor (sIL-2r) from peripheral blood mononuclear cells (PBMC) in 25 Chinese patients with ulcerative colitis and 20 healthy controls.METHODS:PBMC were isolated by density gradient centrifugation of heparinized blood and cultures for 24 or 48 hours by stimulation with LPS or PHA. TNF-alphaand sIL-2r were measured by ELISA method and IL-6 measured by biossay.RESULTS:TNF-alphaproduction stimulated by LPS and sIL-2r production by PHA in ulcerative colitis were significantly lower than in healthy controls (TNF-alpha509(46-7244)ng/L vs 1995(117-18 950)ng/L, P < 0.05; sIL-2r 320U/mlplus minus 165U/ml vs 451U/mlplus minus 247U/ml, P < 0.05).Spontaneous TNF-alphaand sIL-2r production were not significantly different between ulcerative colitis and controls (TNF-alpha304(46-7044)ng/L vs 215(46-4009)ng/L,P > 0.05; sIL-2r 264U/mlplus minus 115U/ml vs 236U/mlplus minus139U/ml, P>0.05). IL-6 production by spontaneous release from PBMC in ulcerative colitis group was 109U/mlplus minus 94U/ml vs 44U/mlplus minus 39U/ml for those in healthy controls, P < 0.01. IL-6 stimulated by LPS in ulcerative colitis group was (261U/ml plus minus 80U/ml) higher than in healthy controls (102U/mlplus minus 54U/ml, P < 0.01). No correlation of TNF-alpha, IL-6, sIL-2r production was found to disease activity, disease location and medication.CONCLUSION:Cytokine production from PBMC was also disturbed in Chinese patients with ulcerative colitis.

Inflammatory Bowel Disease: Definition, Epidemiology, Etiologic Aspects, and Immunogenetic Studies

World Journal of Gastroenterology : WJG. Oct, 1998  |  Pubmed ID: 11819343

Polymorphisms at the TNF Locus in Chinese Han Population

Human Immunology. Jan, 2002  |  Pubmed ID: 11924527

One hundred sixty-four unrelated healthy individuals from Chinese Han population were investigated in order to define the distribution of eight polymorphic loci within the tumor necrosis factor (TNF) gene cluster and determine their relationship between the high polymorphic microsatellite TNFa, b, d, and other elements. The cloning and sequencing for five microsatellites were simultaneously done. In this study, the distribution of TNF alleles apparently vary from other ethnic groups. A new allele was detected and confirmed. It should be emphasized that a very strong association between TNFd8 and TNFe4 is reported and d8e4 haplotype appears to be specific to the population studied. In addition, five extended haplotypes were established in this population: a6b5c1d8e4TNF308-1TNF-betaNco1-1TNFAspH1-2, a2b1c2d5e1TNF308-1TNF-betaNco1-2TNFAspH1-2, a11b4c1d4e3TNF308-1TNF-betaNco1-2TNFAspH1-1, a10b4c1d4e3TNF308-1TNF-betaNco1-2TNFAspH1-1, and a2b3c1d2e3TNF308-2TNFAspH1-2. Data suggest that important ethnic differences may exist and that it is a necessary initiative for further research.

Vitamin C Preserves Endothelial Function in Patients with Coronary Heart Disease After a High-fat Meal

Clinical Cardiology. May, 2002  |  Pubmed ID: 12018880

It has been suggested that an oxidative mechanism is involved with the impaired endothelium-dependent vasodilatation that occurs after a high-fat meal. Hypothesis: The study was undertaken to evaluate the effect of a single oral dose of vitamin C (2 g) on postprandially impaired endothelium-dependent vasodilatation in patients with coronary heart disease (CHD).

[Rapid Inhibition of Extracellular Signal-regulated Kinase 1/2 in a Human Ovarian Cancer Cell Line by Dexamethasone]

Ai Zheng = Aizheng = Chinese Journal of Cancer. Aug, 2002  |  Pubmed ID: 12478895

Activation of extracellular signal-regulated kinase 1/2 (ERK1/2) plays an important role in cell proliferation of a variety of cell types. The authors had previously found that dexamethasone (Dex), a synthetical glucocorticoid, can markedly inhibit the proliferation of a human ovarian cancer cell line HO-8910. This study was designed to observe the effect of Dex on the activation of ERK1/2 in HO-8910 cells in order to explore the signal transduction pathway that mediates the anti-proliferation effect of Dex on these cells.

Topographic Association of Gastric Epithelial Expression of Ki-67, Bax, and Bcl-2 with Antralization in the Gastric Incisura, Body, and Fundus

The American Journal of Gastroenterology. Dec, 2002  |  Pubmed ID: 12492185

Helicobacter pylori (H. pylon) infection seems to induce antralization (ie., gastric mucosal transformation from transitional or body type to antral type), which is strongly associated with gastric atrophy and intestinal metaplasia. The aim of this study was to determine the topographic associations of Ki-67 (a protein expressed in proliferative cells), Bax (a pro-apoptotic protein), and Bcl-2 (an antiapoptotic protein) expression with antralization.

[Synthesis and Monolayer Behaviors of 4-methyl-5-hydroxy-ethyl Isothiazole Stearic Ester]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Dec, 2002  |  Pubmed ID: 12914167

4-methyl-5-hydroxy-ethyl isothiazole stearic ester (HISE) was synthesized and characterized by FTIR spectroscopy, 1H NMR and MS. The monolayer-forming ability of HISE was studied in subphases with different pH values using isotherms of surface pressure-area per molecule (pi-A). It was observed that the collapse pressure and the film-forming ability of the monolayers of HISE increased gradually as pH values ascended. Research of differentiated pi-A curves (d pi(/dA-A) indicated that there were one or two phase change points during the compressing process, and the incompressibility and the stability of HISE monolayers on alkalescent subphases were better than on acid subphases.

The Cold Box Stem-loop Proximal to the 5'-end of the Escherichia Coli CspA Gene Stabilizes Its MRNA at Low Temperature

The Journal of Biological Chemistry. Feb, 2002  |  Pubmed ID: 11741997

The 5'-end region of cspA mRNA contains a Cold Box sequence conserved among several cold-shock mRNAs. This region forms a stable stem-loop structure followed by an AU-rich sequence. Here we show that the Cold Box region is essential for the normal scale of cspA mRNA induction after cold shock because a deletion of the stem-loop significantly destabilizes the mRNA and reduces the cold shock-induced cspA mRNA amount by approximately 50%. The AU-rich track, however, slightly destabilizes the mRNA. The integrity of the stem is essential for the stabilizing function, whereas that of the loop sequence is less important. Overexpression of a mutant cspA mRNA devoid of both the AUG initiation codon and the coding sequence results in a severe growth inhibition at low temperature along with a derepression of the chromosomal cspA expression. Furthermore, the overexpressed RNA is stably associated with the 30 S and 70 S ribosomes. Our results demonstrate that the AUG initiation codon and the coding region containing the downstream box are not required for cspA mRNA to bind ribosomes and that the 5'-untranslated region by itself has a remarkable affinity to ribosomes at low temperature.

Overexpression of the CT GalNAc Transferase in Skeletal Muscle Alters Myofiber Growth, Neuromuscular Structure, and Laminin Expression

Developmental Biology. Feb, 2002  |  Pubmed ID: 11795940

Carbohydrates have been shown to mediate or modulate a number of important events in the development of the nervous system; however, there is little evidence that they participate directly in the development of synapses. One carbohydrate structure that is likely to be important in synaptic development of the neuromuscular junction is the CT carbohydrate antigen [GalNAcbeta1,4[NeuAcalpha2,3]Galbeta1(-3GalNAc or -4GlcNAc)]. The synaptic localization of the CT antigen is due to the presence of the terminal beta1,4 GalNAc linkage, and such linkages are localized to the neuromuscular junction in many species. Here we show that an enzyme that can create the synaptic CT structure, the CT GalNAc transferase, is also confined to the neuromuscular junction in mice. Using transgenic mice, we show that overexpression of the CT GalNAc transferase in extrasynaptic regions in skeletal myofibers caused as much as a 60% reduction in the diameter of adult myofibers and an order of magnitude increase in satellite cells. Neuromuscular junctions of transgenic mice had severely reduced numbers of secondary folds, Schwann cell processes were present in the synaptic cleft, and secondary folds were often misaligned with active zones. In addition, multiple presynaptic specializations occurred on individual myofibers. In addition, some normally synaptic proteins, including laminin alpha4, laminin alpha5, utrophin, and NCAM, were expressed along extrasynaptic regions of myofibers. One of the muscle proteins that displayed increased glycosylation with the CT antigen in the transgenic mice was alpha-dystroglycan. These experiments provide the first in vivo evidence that a synaptic carbohydrate antigen has important roles in the development of the neuromuscular synapse and suggest that the CT antigen is involved in controlling the expression of synaptic molecules.

Overexpression of the Cytotoxic T Cell GalNAc Transferase in Skeletal Muscle Inhibits Muscular Dystrophy in Mdx Mice

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2002  |  Pubmed ID: 11960016

Duchenne muscular dystrophy (DMD) is a congenital X-linked myopathy caused by lack of dystrophin protein expression. In DMD, the expression of many dystrophin-associated proteins (DAPs) is reduced along the sarcolemmal membrane, but the same proteins remain concentrated at the neuromuscular junction where utrophin, a dystrophin homologue, is expressed [Matsumura, K., Ervasti, J. M., Ohlendieck, K., Kahl, K. D. & Campbell, K. (1992) Nature (London) 360, 588-591]. This outcome has led to the concept that ectopic expression of a "synaptic scaffold" of DAPs and utrophin along myofibers might compensate for the molecular defects in DMD. Here we show that transgenic overexpression of the synaptic CT GalNAc transferase in the skeletal muscles of mdx animals (mdx/CT) increases the expression of utrophin and many DAPs, including dystroglycans, sarcoglycans, and dystrobrevins, along myofibers. Protein expression of utrophin and DAPs was equal to or above that of wild-type mice. In addition, alpha-dystroglycan was glycosylated with the CT carbohydrate antigen in mdx/CT but not in mdx muscles. mdx/CT mice have little or no evidence of muscular dystrophy by several standard measures; Serum creatine kinase levels, percentage of centrally located myofiber nuclei, and variance in myofiber diameter in mdx/CT muscles were dramatically reduced compared with mdx mice. These data suggest that ectopic expression of the CT GalNAc transferase creates a functional dystrophin-related complex along myofibers in the absence of dystrophin and should be considered as a target for therapeutic intervention in DMD.

Modulation of Agrin Binding and Activity by the CT and Related Carbohydrate Antigens

Molecular and Cellular Neurosciences. Apr, 2002  |  Pubmed ID: 11988021

Agrin is a nerve-derived signal that is essential for the proper organization of postsynaptic acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction. It is likely that carbohydrates play a significant role in regulating agrin activity, as agrin binds multiple glycan structures and is itself a highly glycosylated protein. Here we provide support for this contention by showing that agrin can be modified with the CT antigen, a carbohydrate structure expressed at the neuromuscular junction, and by describing the resulting changes in agrin binding to neoglycoconjugates and cultured myotubes, as well as changes in agrin-dependent AChR clustering. Glycosylation of agrin with the CT antigen required the mucin domain and the dystroglycan/heparin-binding domain. The presence of the mucin domain lowered agrin binding to several N-acetyllactosaminyl-containing saccharides and C2 myotubes and lowered agrin activity in AChR clustering. Glycosylation of agrin with the CT antigen, by contrast, increased agrin binding to myotubes and potentiated its AChR clustering activity at subsaturating concentrations. Last, sialylated and nonsialylated variants of N-acetyllactosamine differentially modulated AChR clustering and agrin activity, and these changes correlated with the ability of MuSK, an agrin-stimulated kinase, to bind to these structures. These experiments demonstrate that the glycosylation state of agrin affects its activity and suggest a role for the CT antigen in modulating agrin function.

Solution NMR Structure of Ribosome-binding Factor A (RbfA), a Cold-shock Adaptation Protein from Escherichia Coli

Journal of Molecular Biology. Mar, 2003  |  Pubmed ID: 12628255

Ribosome-binding factor A (RbfA) from Escherichia coli is a cold-shock adaptation protein. It is essential for efficient processing of 16S rRNA and is suspected to interact with the 5'-terminal helix (helix I) of 16S rRNA. RbfA is a member of a large family of small proteins found in most bacterial organisms, making it an important target for structural proteomics. Here, we describe the three-dimensional structure of RbfADelta25, a 108 residue construct with 25 residues removed from the carboxyl terminus of full-length RbfA, determined in solution at pH 5.0 by heteronuclear NMR methods. The structure determination was carried out using largely automated methods for determining resonance assignments, interpreting nuclear Overhauser effect (NOE) spectroscopy (NOESY) spectra, and structure generation. RbfADelta25 has an alpha+beta fold containing three helices and three beta-strands, alpha1-beta1-beta2-alpha2-alpha3-beta3. The structure has type-II KH-domain fold topology, related to conserved KH sequence family proteins whose betaalphaalphabeta subunits are characterized by a helix-turn-helix motif with sequence signature GxxG at the turn. In RbfA, this betaalphaalphabeta subunit is characterized by a helix-kink-helix motif in which the GxxG sequence is replaced by a conserved AxG sequence, including a strongly conserved Ala residue at position 75 forming an interhelical kink. The electrostatic field distribution about RbfADelta25 is bipolar; one side of the molecule is strongly negative and the opposite face has a strong positive electrostatic field. A "dynamic hot spot" of RbfADelta25 has been identified in the vicinity of a beta-bulge at strongly conserved residue Ser39 by 15N R(1), R(2) relaxation rate and heteronuclear 15N-1H NOE measurements. Analyses of these distributions of electrostatic field and internal dynamics, together with evolutionary implications of fold and sequence conservation, suggest that RbfA is indeed a nucleic acid-binding protein, and identify a potential RNA-binding site in or around the conserved polypeptide segment Ser76-Asp100 corresponding to the alpha3-loop-beta3 helix-loop-strand structure. While the structure of RbfADelta25 is most similar to that of the KH domain of the E.coli Era GTPase, its electrostatic field distribution is most similar to the KH1 domain of the NusA protein from Thermotoga maritima, another cold-shock associated RNA-binding protein. Both RbfA and NusA are regulated in the same E.coli operon. Structural and functional similarities between RbfA, NusA, and other bacterial type II KH domains suggest previously unsuspected evolutionary relationships between these cold-shock associated proteins.

Overexpression of the CT GalNAc Transferase Inhibits Muscular Dystrophy in a Cleavage-resistant Dystroglycan Mutant Mouse

Biochemical and Biophysical Research Communications. Mar, 2003  |  Pubmed ID: 12646245

Transgenic mice that express dystroglycan containing a serine to alanine point mutation at the normal site of cleavage (DG(S654A)) in their skeletal muscles fail to express endogenously cleaved dystroglycan and have muscular dystrophy [Neuromusc. Disord., in press]. Dystrophic DG(S654A) muscles have reduced binding of antibodies, including VIA4-1, that recognize carbohydrate antigens on alpha dystroglycan, a finding similar to muscles in some forms of congenital muscular dystrophy. Here we describe one DG(S654A) transgenic line where VIA4-1 antibody binding is absent in skeletal muscle. In theory, the absence of this carbohydrate antigen should inhibit later glycosylation events that would occur on the structure or structures this antibody binds to. One such modification is likely to be the CT carbohydrate antigen, which is present on alpha dystroglycan in muscles overexpressing the CT GalNAc transferase [Dev. Biol. 242 (2002) 58]. To test the relationship between the VIA4-1 and CT carbohydrate antigens, we made DG(S654A)/CT GalNAc transferase (DG(S654A)/CT) transgenic mice. Surprisingly, dystroglycan was cleaved, and alpha dystroglycan was glycosylated with the VIA4-1 antigen, in DG(S654A)/CT muscles. In addition, muscles in DG(S654A)/CT transgenic mice had little or no evidence of muscular dystrophy when compared to DG(S654A) littermates. These experiments demonstrate that the CT GalNAc transferase can affect the post-translational processing of dystroglycan and the extent of muscular dystrophy even in muscles where the VIA4-1 antigen is not present.

[Synthesis, Characterization and Properties of N,N-dimethylferrocenylmethylhexadecylammonium Bromide]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Jun, 2003  |  Pubmed ID: 12953532

N,N-dimethylferrocenylmethylhexadecylammonium bromide (FC16AB) was synthesized and characterized by the spectra of UV-Visible, FTIR 1H NMR, ESMS, etc. Surface tensions of different concentrations of FC16AB water solution were measured, which shows that FC16AB has good surface activity. The surface pressure-area (pi-A) curves and differentiated pi-A curves of FC16AB on water, Cl-, and SO(4)2- subphases were studied. The results indicate that FC16AB molecules can form the most stable monolayer on the subphase containing Cl-.

The Role of RbfA in 16S RRNA Processing and Cell Growth at Low Temperature in Escherichia Coli

Journal of Molecular Biology. Sep, 2003  |  Pubmed ID: 12963368

RbfA, a 30S ribosome-binding factor, is a multicopy suppressor of a cold-sensitive C23U mutation of the 16S rRNA and is required for efficient processing of the 16S rRNA. At 37 degrees C, DeltarbfA cells show accumulation of ribosomal subunits and 16S rRNA precursor with a significantly reduced polysome profile in comparison with wild-type cells. RbfA is also a cold-shock protein essential for Escherichia coli cells to adapt to low temperature. In this study, we examined its association with the ribosome and its role in 16S rRNA processing and ribosome profiles at low temperature. In wild-type cells, following cold shock at 15 degrees C, the amount of free RbfA remained largely stable, while that of its 30S subunit-associated form became several times greater than that at 37 degrees C and a larger fraction of total 30S subunits was detected to be RbfA-containing. In DeltarbfA cells, the pre-16S rRNA amount increased after cold shock with a concomitant reduction of the mature 16S rRNA amount and the formation of polysomes was further reduced. A closer examination revealed that 30S ribosomal subunits of DeltarbfA cells at low temperature contained primarily pre-16S rRNA and little mature 16S rRNA. Our results indicate that the cold sensitivity of DeltarbfA cells is directly related to their lack of translation initiation-capable 30S subunits containing mature 16S rRNA at low temperature. Importantly, when the C-terminal 25 residue sequence was deleted, the resulting RbfADelta25 lost the abilities to stably associate with the 30S subunit and to suppress the dominant-negative, cold-sensitive phenotype of the C23U mutation in 16S rRNA but was able to suppress the 16S rRNA processing defect and the cold-sensitive phenotype of the DeltarbfA cells, suggesting that RbfA may interact with the 30S ribosome at more than one site or function in more than one fashion in assisting the 16S rRNA maturation at low temperature.

Enhancement of Translation Initiation by A/T-rich Sequences Downstream of the Initiation Codon in Escherichia Coli

Journal of Molecular Microbiology and Biotechnology. 2003  |  Pubmed ID: 15153766

The region located downstream of the initiation codon constitutes part of the translation initiation signal, significantly affecting the level of protein expression in E. coli. In order to determine its influence on translation initiation, we inserted random 12-base sequences downstream of the initiation codon of the lacZ gene. A total of 119 random clones showing higher beta-galactosidase activities than the control lacZ gene were isolated and subsequently sequenced. Analysis of these clones revealed that their insertion sequences are strikingly rich in A and T, but poor in G, with no consensus sequences among them. Toeprinting experiments and polysome profile analysis confirmed that the A/T-rich sequences enhance translation at the level of initiation. Collectively, the present data demonstrate that A/T richness of the region following the initiation codon plays a significant role in E. coli gene expression.

Inhibition of Dystroglycan Cleavage Causes Muscular Dystrophy in Transgenic Mice

Neuromuscular Disorders : NMD. Jun, 2003  |  Pubmed ID: 12798792

Dystroglycan (DG) is an essential component of the dystrophin-glycoprotein complex, a molecular scaffold that links the extracellular matrix to the actin cytoskeleton. Dystroglycan protein is post-translationally cleaved into alpha dystroglycan, a highly glycosylated peripheral membrane protein, and beta dystroglycan, a transmembrane protein. Despite clear evidence of the importance of dystroglycan and its associated proteins in muscular dystrophy, the purpose of dystroglycan proteolysis is unclear. By introducing a point mutation at the normal site of proteolysis (serine 654 to alanine, DGS654A), we have created a dystroglycan protein that is severely inhibited in its cleavage. Transgenic expression of DGS654A in mouse skeletal muscles inhibited the expression of endogenously cleaved dystroglycan, while overexpression of wild type dystroglycan by similar amounts did not. DGS654A animals had increased serum creatine kinase activity and most muscles had increased numbers of central nuclei. Overexpression of wild type dystroglycan, by contrast, caused no dystrophy by these measures. Dystrophy in DGS654A muscles correlated with reduced binding of antibodies that recognize glycosylated forms of alpha dystroglycan. Lastly, neuromuscular junctions in DGS654A muscles were aberrant in structure. These data show that aberrant processing of the dystroglycan polypeptide causes muscular dystrophy and suggest that dystroglycan processing is important for the proper glycosylation of alpha dystroglycan.

CTLA-4 and CD28 Gene Polymorphisms in Susceptibility, Clinical Course and Progression of Multiple Sclerosis

Journal of Neuroimmunology. Jul, 2003  |  Pubmed ID: 12864988

The balance between CD28 and CTLA-4 signalling is important for regulation of the immune response. We were interested whether a genetically mediated disturbance of this balance could be related to susceptibility or severity of multiple sclerosis (MS). We examined three polymorphisms in these genes, CTLA-4-318, CTLA-4+49 and CD28-I3+17, in 514 patients with MS and 181 controls. As the loci cannot be assumed independent of each other, we analysed the effects of each of the three polymorphisms corrected for the presence of the other two. We found no association between carriership of any of the alleles either with susceptibility to MS or with clinical features. For a subgroup of patients, longitudinal magnetic resonance imaging (MRI) data were available. We observed no effects of the polymorphisms on brain and lesion volumes. These data suggest that the polymorphisms under investigation do not affect the risk of developing MS and have no influence on the course of disease.

Glucocorticoid Modulation of Extracellular Signal-regulated Protein Kinase 1/2 and P38 in Human Ovarian Cancer HO-8910 Cells

Chinese Medical Journal. May, 2003  |  Pubmed ID: 12875695

To investigate the signaling pathway through testing the effects of dexamethasone (Dex) on the activation of the extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38 kinase (p38) in HO-8910 cells.

Cold-shock Induced High-yield Protein Production in Escherichia Coli

Nature Biotechnology. Jul, 2004  |  Pubmed ID: 15195104

Overexpression of proteins in Escherichia coli at low temperature improves their solubility and stability. Here, we apply the unique features of the cspA gene to develop a series of expression vectors, termed pCold vectors, that drive the high expression of cloned genes upon induction by cold-shock. Several proteins were produced with very high yields, including E. coli EnvZ ATP-binding domain (EnvZ-B) and Xenopus laevis calmodulin (CaM). The pCold vector system can also be used to selectively enrich target proteins with isotopes to study their properties in cell lysates using NMR spectroscopy. We have cloned 38 genes from a range of prokaryotic and eukaryotic organisms into both pCold and pET14 (ref. 3) systems, and found that pCold vectors are highly complementary to the widely used pET vectors.

[Study of Muscle Pressure Exerted on Deciduous Normal Occlusion]

Zhejiang Da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences. Jul, 2004  |  Pubmed ID: 15269988

To measure the muscle pressure exerted on the deciduous normal occlusion and to explore the relationship between the denture,occlusion, skeleton and muscle pressure.

Transgenic Overexpression of Dystroglycan Does Not Inhibit Muscular Dystrophy in Mdx Mice

The American Journal of Pathology. Feb, 2004  |  Pubmed ID: 14742274

Recently, there have been a number of studies demonstrating that overexpression of molecules in skeletal muscle can inhibit or ameliorate aspects of muscular dystrophy in the mdx mouse, a model for Duchenne muscular dystrophy. Several such studies involve molecules that increase the expression of dystroglycan, an important component of the dystrophin-glycoprotein complex. To test whether dystroglycan itself inhibits muscular dystrophy in mdx mice, we created dystroglycan transgenic mdx mice (DG/mdx). The alpha and beta chains of dystroglycan were highly overexpressed along the sarcolemmal membrane in most DG/mdx muscles. Increased dystroglycan expression, however, did not correlate with increased expression of utrophin or sarcoglycans, but rather caused their decreased expression. In addition, the percentage of centrally located myofiber nuclei and the level of serum creatine kinase activity were not decreased in DG/mdx mice relative to mdx animals. Therefore, dystroglycan overexpression does not cause the concomitant overexpression of a utrophin-glycoprotein complex in mdx muscles and has no effect on the development of muscle pathology associated with muscular dystrophy.

Effects of Low Molecular Weight Heparin on Platelet Surface P-selectin Expression and Serum Interleukin-8 Production in Rats with Trinitrobenzene Sulphonic Acid-induced Colitis

World Journal of Gastroenterology : WJG. Mar, 2004  |  Pubmed ID: 14991948

To observe the effects of low molecular weight heparin (LMWH) on platelet surface P-selectin expression and serum interleukin-8 production in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis.

NOD2 3020insC Frameshift Mutation is Not Associated with Inflammatory Bowel Disease in Chinese Patients of Han Nationality

World Journal of Gastroenterology : WJG. Apr, 2004  |  Pubmed ID: 15052696

An insertion mutation at nucleotide 3020 (3020insC) in the Caspase recruitment domain gene (CARD15), originally reported as NOD2, is strongly associated with Crohn's disease. The C-insertion mutation at nucleotide 3020 (3020inC) in the leucine-rich repeat (LRR) region results in a frameshift in the 10(th) LRR followed by a premature stop codon. This truncation mutation is responsible for the inability to activate nuclear factor (NF)-kappaB in response to bacterial lipopolysaccharide (LPS). The present study aimed to genotype NOD2/CARD15 gene 3020insC frameshift mutation in Chinese patients with inflammatory bowel disease.

[Association Between the Cytotoxic T Lymphocyte Antigen-4 Gene Microsatellite Polymorphism and Inflammatory Bowel Diseases in the Chinese]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Mar, 2004  |  Pubmed ID: 15059373

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation as a result of an exaggerated T-cell response. Cytotoxic T lymphocyte antigen-4 (CTLA-4) expressed mainly on activated T cells, inhibits T cell activation by combining B(7) through competing CD(28) and maintains immune system homeostasis. Polymorphisms in the CTLA-4 gene are known to be associated with several autoimmune diseases, but no studies related to IBD. The aim of the study is to investigate an association between CTLA-4 gene microsatellite polymorphisms and IBD.

Association of Tumor Necrosis Factor Genetic Polymorphism with Chronic Atrophic Gastritis and Gastric Adenocarcinoma in Chinese Han Population

World Journal of Gastroenterology : WJG. May, 2004  |  Pubmed ID: 15112338

To investigate the association of TNF polymorphisms with chronic atrophic gastritis (CAG) and gastric adenocarcinoma in Chinese Han patients.

Association of Fas-670 Gene Polymorphism with Inflammatory Bowel Disease in Chinese Patients

World Journal of Gastroenterology : WJG. Jan, 2005  |  Pubmed ID: 15637757

Recent studies suggest that Fas-mediated apoptosis is involved in the pathogenesis of inflammatory bowel disease (IBD). It has been hypothesized that either increased apoptosis of intestinal epithelium or decreased apoptosis of lamina propria lymphocytes may induce inflammation of gut. The aim of this study was to determine whether the Fas gene promoter polymorphism at position-670 was associated with IBD in Chinese patients.

TNF Gene Polymorphisms and Helicobacter Pylori Infection in Gastric Carcinogenesis in Chinese Population

The American Journal of Gastroenterology. Feb, 2005  |  Pubmed ID: 15667484

Helicobacter pylori (H. pylori) is a major cause of chronic gastritis and peptic ulcer disease, and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms have not been fully understood although the interactions between environmental, bacterial, and multiple genetic components are likely to be involved. Tumor necrosis factor (TNF) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine the di-allelic polymorphisms of TNF gene and their association with H. pylori infection and gastroduodenal diseases in Chinese population of Han nationality.

Use of a Simple Intraoral Instrument to Standardize Film Alignment and Improve Image Reproducibility

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. Jul, 2005  |  Pubmed ID: 15953923

A lot of instruments and devices were reported in standardized realignment of intraoral film. However, these instruments either are too cumbersome and time consuming to be used or require extensive fabrication. In this study we described a prototype of a instrument for realignment of intraoral film and evalated its reproducibility.

Reaction of Porous Silicon with Both End-functionalized Organic Compounds Bearing Alpha-bromo and Omega-carboxy Groups for Immobilization of Biomolecules

The Journal of Physical Chemistry. B. Nov, 2005  |  Pubmed ID: 16853669

Both end-functionalized (alpha-bromo and omega-carboxy) compounds were first tested for the radical reaction on the silicon-hydride (Si-H) terminated porous silicon (PSi) with/without the presence of diacyl peroxide initiator under microwave irradiation. Then the carboxylic acid monolayers (CAMs) assembled on PSi through the robust Si-C bonds were converted to amino-reactive linker, N-hydroxysuccinimide (NHS)-ester, terminated monolayers. And finally two proteins of bovine serum albumin (BSA) and lysozyme (Lys) were immobilized through amide bonds. The optimum PSi membrane for protein immobilization without collapse, with parameters of porous radii 4-10 nm and depth 0.2-4.6 mum, was prepared from the (100)-oriented p-type silicon wafer. The chemically converted surface products were monitored with Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and field emission scanning electron microscopy (FESEM).

CTLA-4 Gene Polymorphisms in Chinese Patients with Ulcerative Colitis

Inflammatory Bowel Diseases. Jul, 2005  |  Pubmed ID: 15973119

Ulcerative colitis (UC) is characterized by chronic inflammation of the colon and rectum as a result of an exaggerated T-cell response. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a T cell-restricted surface molecule induced with TCR or CD28 activation. There is evidence for genetic involvement of CTLA-4 in several autoimmune diseases, with the focus on the possible role of genetic variation of the CTLA-4 locus. The aim of this study was to investigate CTLA-4 gene polymorphisms in patients with UC in a Chinese population with Han nationality.

MHC Class I Chain-related Gene A-A5.1 Allele is Associated with Ulcerative Colitis in Chinese Population

Clinical and Experimental Immunology. Oct, 2005  |  Pubmed ID: 16178876

The human MHC class I chain-related gene A (MICA) plays a role in regulating protective responses by intestinal epithelial Vdelta1 gamma delta T cells and the polymorphism of MICA were reported to be related to several autoimmune diseases. The present study aimed to investigate the association of the microsatellite polymorphisms of TM region of MICA gene with the susceptibility to ulcerative colitis (UC) in Chinese population. The microsatellite polymorphisms of the MICA were genotyped in unrelated 86 Chinese patients with UC and 172 ethnically matched healthy controls by a semiautomatic fluorenscently labelled PCR method. All the subjects were the Chinese with Han nationality. The frequency of MICA-A5.1 homozygous genotype and A5.1 allele were significantly increased in UC patients compared with healthy controls (22.1%versus 7%, P = 0.0009, Pc = 0.0126, OR = 3.781, 95%CI: 1.738-8.225 and 30.2%versus 17.4%, P = 0.0014, Pc = 0.007, OR = 2.051, 95%CI: 1.336-3.148, respectively). Adjusted the effects of gender and age at onset, MICA-A5.1 homozygous genotype and A5.1 allele were also increased in the UC patients. Moreover MICA-A5.1 allele was significantly increased in frequency in the female UC patients (38.2%versus 21.0%, P = 0.0095, Pc = 0.0475, OR = 2.326, 95%CI: 1.234-4.382). Logistic regression analysis also revealed that gender was independently associated with UC patients carried MICA-A5.1 allele (P = 0.046, OR (male) = 0.511, 95% CI: 0.264-0.987). Although the UC patients with extensive colitis (32.5%versus 17.4% in the healthy controls, P = 0.005, Pc = 0.025) and the UC patients with extraintestinal manifestations (36%versus 17.4% in the healthy controls, P = 0.0039, Pc = 0.0195) were more likely to carry the MICA-A5.1 allele, EIMs was associated with extent of disease (P < 0.0001, OR (with EIMs) = 3.511, 95% CI 1.747-7.056) and MICA-A5.1 allele was not associated with UC patients with extensive colitis or with EIMs in the logistic regression analysis. Therefore, the MICA-A5.1 homozygous genotype and A5.1 allele were closely associated with UC and the MICA-A5.1 allele was positively associated with the female UC patients in Chinese population.

Aptamers That Preferentially Bind Type IVB Pili and Inhibit Human Monocytic-cell Invasion by Salmonella Enterica Serovar Typhi

Antimicrobial Agents and Chemotherapy. Oct, 2005  |  Pubmed ID: 16189080

Salmonella enterica serovar Typhi is an important pathogen exclusively for humans and causes typhoid or enteric fever. It has been shown that type IVB pili, encoded by the S. enterica serovar Typhi pil operon located in Salmonella pathogenicity island 7, are important in the pathogenic process. In this study, by using both an adhesion-invasion assay and fluorescence quantitative PCR analysis, we demonstrated that the entry of type IVB piliated S. enterica serovar Typhi A21-6 (pil(+) Km(r)) into human THP-1 monocytic cells was greater than that of a nonpiliated S. enterica serovar Typhi pilS::Km(r) (pil mutant) strain. We have applied a systematic evolution of ligands by exponential enrichment approach to select oligonucleotides (aptamers) as ligands that specifically bind to type IVB pili. Using this approach, we identified a high-affinity single-stranded RNA aptamer (S-PS(8.4)) as a type IVB pilus-specific ligand and further found that the selected aptamer (S-PS(8.4)) could significantly inhibit the entry of the piliated strain (but not that of the nonpiliated strain) into human THP-1 cells. The binding affinities between aptamers and pre-PilS (structural protein of type IVB pili) were determined by nitrocellulose filter-binding assays, and the K(d) value was determined to be 8.56 nM for the S-PS(8.4) aptamer alone. As an example of an aptamer against type IVB pili of S. enterica serovar Typhi, the aptamer S-PS(8.4) can serve as a tool for analysis of bacterial type IVB pilus-host cell interactions and may yield information for the development of putative new drugs against S. enterica serovar Typhi bacterial infections, useful both in prevention of infection and in therapeutic treatment.

Application of 3' Untranslated Region (UTR) Sequence-based Amplified Polymorphism Analysis in the Rapid Authentication of Radix Astragali

Journal of Agricultural and Food Chemistry. Nov, 2005  |  Pubmed ID: 16248552

Radix astragali (root of Astragalus membranaceus) is an important traditional Chinese medicine. It has been used as a tonic herb for thousands of years in China. The water extract of the roots has a wide range of immunopotentiating effects and has been proven to be efficacious as an adjunct cancer therapy. Authentication of the herbal plant is routinely required for general practice in the field of herbal medicine. To facilitate rapid identification of numerous varieties of Radix astragali that are circulating on the herb markets, a rapid molecular genetic method, named 3' untranslated region (3' UTR) sequence-based amplified polymorphism (UAP), has been developed. A cDNA library was first built from transcripts of an authentic A. membranaceus species. Several cDNA clones specific to A. membranaceus were identified through subtractive hybridization of the A. membranaceus cDNA library with Arabidopsis total cellular RNA. On the basis of these cDNA sequences of the 3' untranslated region (3' UTR) of selected cDNA clones, a Polymerase Chain Reaction (PCR) was performed on genomic DNAs of the dry roots of several putative A. membranaceus. PCR fragment length polymorphism was found between A. membranaceus and its relatives. By using this method, it was possible to differentiate the authentic A. membranaceus root from those putative ones obtained from herbal medicine markets. To the authors' knowledge, this is the first paper applying UAP in the authentication of traditional Chinese medicine plants.

Diffusion of Hydrosilanes from the Control Layer to the Vinylsilane-rich Flow Membrane During the Fabrication of Microfluidic Chips

Langmuir : the ACS Journal of Surfaces and Colloids. Nov, 2005  |  Pubmed ID: 16262310

During the fabrication of poly(dimethylsiloxane) (PDMS)-based microfluidic chips, polymethylhydrosiloxane (PMHS) species in the control layer diffuse into the flow membrane, which contains polymethylvinylsiloxane (PMVS), and the components cross-link together to form the mechanically enhanced membrane. The diffusion course was investigated by using attenuated total reflectance FTIR and the improvement of mechanical properties of the flow membrane was studied by measuring the Young's modulus and the tensile strength.

Study of Cis-cinnamic Acid in Arabidopsis Thaliana

Plant Physiology and Biochemistry : PPB / Société Française De Physiologie Végétale. Oct-Nov, 2005  |  Pubmed ID: 16310363

Trans-cinnamic acid (CA) can be isomerized to cis-CA in Arabidopsis thaliana extract under sunlight. Piperonylic acid treatment of Arabidopsis under ultraviolet (UV) light increased the level of cis-CA in these treated tissues. Similarly, cis-CA was also detected from Oryza sativa seedlings grown under sunlight. These results suggest that cis-CA may occur in planta. Application of cis-CA to seedlings of both wild type Arabidopsis and auxin-insensitive mutants, aux1 and axr2, resulted in nearly identical dose response curves in root growth, indicating that the mode of action by which cis-CA affects plant growth is different from that of auxins. According to root growth inhibition assay, cis-CA is nearly 10 times more active than trans-CA. These results suggest that cis-CA is a unique plant growth regulator but its in vivo function remains to be elucidated.

Matrine Improves 2,4,6-trinitrobenzene Sulfonic Acid-induced Colitis in Mice

Pharmacological Research : the Official Journal of the Italian Pharmacological Society. Mar, 2006  |  Pubmed ID: 16332442

Matrine is an alkaloid found in kinds of Sophora plants mainly including Sophora flavescens, Sophora alopecuroides and Sophora subprotrata. The aim of the present study was to evaluate therapeutic effects of matrine on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Two hours following colonic instillation of TNBS, matrine with several doses was given by gastric gavage once daily for 7 days. Comparing with the 0.9% NaCl-treated mice with TNBS-induced colitis, matrine (10 and 20 mg kg(-1))-treated mice with TNBS-induced colitis were shown improvements of weight loss, macroscopic score, histological score, and myeloperoxidase (MPO) activity. Moreover, treatments with matrine (10 and 20 mg kg(-1)) decreased the up-regulated mRNA and protein levels of tumour necrosis factor-alpha (TNF-alpha) caused by TNBS. Our findings suggest that matrine improves TNBS-induced colitis in mice and the therapeutic mechanism might be related to the reduction of up-regulated colonic TNF-alpha production caused by TNBS.

Retrospective Survey of 452 Patients with Inflammatory Bowel Disease in Wuhan City, Central China

Inflammatory Bowel Diseases. Mar, 2006  |  Pubmed ID: 16534423

Inflammatory bowel disease (IBD) had been uncommon in China until about 1990, but since then, it has been seen in the clinical setting more and more. The prevalence and phenotype of IBD in the Chinese population is not well known. The present study investigates the trend of prevalence in ulcerative colitis (UC) and Crohn's disease (CD) in Wuhan City, central China, and evaluates clinical features, extraintestinal manifestations, and the treatment of IBD in the last 14 years.

MICB Microsatellite Polymorphism is Associated with Ulcerative Colitis in Chinese Population

Clinical Immunology (Orlando, Fla.). Aug, 2006  |  Pubmed ID: 16679067

The MHC class I-related molecules A and B (MICA and MICB) are stress-inducible cell surface antigens that are recognized by immunocytes bearing the receptor NKG2D, including intestinal epithelial Vdelta1 gammadelta T cells, which may play a role in immunological reaction in intestinal mucosa. The present study was aimed to investigate the association of the microsatellite polymorphisms in the intron 1 of MICB and the MICA-MICB haplotype with the susceptibility to ulcerative colitis (UC) in Chinese population. The microsatellite polymorphisms of MICB were genotyped in unrelated 127 Chinese patients with UC and 193 ethnically matched healthy controls by a semiautomatic fluorescently labeled PCR method. All the subjects were the Chinese with Han nationality. The frequency of MICB-CA18 was significantly higher in UC patients compared with the healthy controls (14.0% vs. 5.8%, P = 0.0016, Pc = 0.024, OR = 2.637, 95%CI: 1.443-4.820) and was increased in the female patients compared with the female healthy controls (18.3% vs. 4.1%, P = 0.0006, Pc = 0.0080, OR = 5.224, 95%CI: 1.940-14.069). Thus, MICB-CA18 is positively associated with UC and female UC patients in Chinese population.

Polymorphism of CD14 Gene but Not the Mutation of TLR4 Gene is Associated with Colorectal Cancer in Chinese Patients

Journal of Gastroenterology and Hepatology. Jan, 2006  |  Pubmed ID: 16706818

Toll-like receptor 4 and CD14 are components of the lipopolysaccharide receptor complex. Our study aimed to investigate an association between TLR4 Asp299Gly and CD14-260 polymorphisms in Chinese patients with colorectal cancer.

Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2

Molecular Cell. Jun, 2006  |  Pubmed ID: 16793542

BRCA2 mutations predispose carriers to breast and ovarian cancer and can also cause other cancers and Fanconi anemia. BRCA2 acts as a "caretaker" of genome integrity by enabling homologous recombination (HR)-based, error-free DNA double-strand break repair (DSBR) and intra-S phase DNA damage checkpoint control. Described here is the identification of PALB2, a BRCA2 binding protein. PALB2 colocalizes with BRCA2 in nuclear foci, promotes its localization and stability in key nuclear structures (e.g., chromatin and nuclear matrix), and enables its recombinational repair and checkpoint functions. In addition, multiple, germline BRCA2 missense mutations identified in breast cancer patients but of heretofore unknown biological/clinical consequence appear to disrupt PALB2 binding and disable BRCA2 HR/DSBR function. Thus, PALB2 licenses key cellular biochemical properties of BRCA2 and ensures its tumor suppression function.

[Cytotoxic T Lymphocyte Antigen-4 Promoter Gene Polymorphism is Significantly Associated with Ulcerative Colitis]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Jun, 2006  |  Pubmed ID: 16831326

Inflammatory bowel disease (IBD) is characterized by the T-cell excessive activation of intestinal mucosa. Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) is a negative regulator of T-lymphocyte activation. The aim of the present study is to investigate the association between CTLA-4 promoter -1722 (T/C), -1661 (A/G) polymorphisms and ulcerative colitis (UC) in Han Chinese, in Hubei province of central China.

Association of CTLA-4 Gene Microsatellite Polymorphism with Ulcerative Colitis in Chinese Patients

Inflammatory Bowel Diseases. May, 2006  |  Pubmed ID: 16670525

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation as a result of an exaggerated T cell response. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), expressed mainly in activated T cells, inhibits T cell activation and proliferation by combining B7 through competing CD28 and maintains immune homeostasis. Polymorphisms of the CTLA-4 gene are known to be associated with several autoimmune diseases. The aim of this study was to investigate the association between the CTLA-4 gene microsatellite polymorphism and UC in Chinese patients. Unrelated 100 Chinese patients with UC and 140 healthy controls were studied. The (AT) repeats in the 3' untranslated region of exon 4 of the CTLA-4 gene were amplified by allele-specific polymerase chain reaction (PCR). The amplified products were electrophoresed on a 12% polyacrylamide gel, followed by silver staining. Twenty alleles were found in Chinese patients and healthy controls. The 122-bp allele was increased in UC compared with healthy controls (9.5% vs 0.7%, P = 0.0001/Pc = 0.002, OR = 14.591, 95%CI 3.357-63.420). The frequency of the longer alleles (>or=118 bp) of UC was higher than that in healthy controls (26% vs 4%, P = 0.0001/Pc = 0.0002, OR = 7.644, 95%CI 3.950-14.792), but was not associated with location and severity of the disease. Furthermore, the longer alleles were not associated with haplotypes of C-318T/A+49G of the CTLA-4 gene in Chinese patients with UC. The longer alleles of the CTLA-4 gene microsatellite polymorphism were strongly associated with UC in Chinese patients.

[Serum Angiogenin Concentration in Nasopharyngeal Carcinoma Patients and Its Clinical Significance]

Lin Chuang Er Bi Yan Hou Ke Za Zhi = Journal of Clinical Otorhinolaryngology. Jul, 2006  |  Pubmed ID: 17017190

To determine the serum angiogenin (ANG) concentration in patients with nasopharyngeal carcinoma (NPC) and analyze its clinical significance.

Distribution of Signal Transducer and Activator of Transcription 6 Gene G2964A Polymorphism in Chinese Patients with Ulcerative Colitis

Journal of Gastroenterology and Hepatology. Dec, 2006  |  Pubmed ID: 17074026

The signal transducer and activator of transcription 6 (STAT6) gene is located on chromosome 12q13.3-14.1 just within the IBD2 region and is a key transcription factor involved in interleukin (IL)-4 and IL-13-mediated Th2 response. The aim of the present study was to determine distribution of the STAT6 gene polymorphism in Chinese patients with ulcerative colitis.

Metal Acetylacetonate Domains Grown on H-terminated Porous Silicon at Room Temperature and Their Specific I-V Behavior

The Journal of Physical Chemistry. B. Dec, 2006  |  Pubmed ID: 17134216

Porous silicon (PS) was incubated in an organic solution of metal acetylacetonates of Mn(acac)(3), Fe(acac)(3), Co(acac)(3), and Ni(acac)(2) (acac = MeCOCHCOMe) at room temperature. Crystal-like domains were found to be spontaneously self-assembled on PS surfaces by atomic force microscopy (AFM). Spectroscopic studies with attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) revealed that the domains were grown from metal acetylacetonates. Current sensing atomic force microscopy (CSAFM) was used to measure the I-V curves of domains in nanoscale and specific step-jump currents on the manganese and cobalt acetylacetonate domains were surprisingly detected.

Nonlithographic Fabrication of Microfluidic Devices

Journal of the American Chemical Society. Dec, 2006  |  Pubmed ID: 17165759

A facile nonlithographic method for expedient fabrication of microfluidic devices of poly(dimethylsiloxane) is described. Positive-relief masters for the molds are directly printed on smooth substrates. For the formation of connecting channels and chambers inside the polymer components of the microfluidic devices, cavity-forming elements are adhered to the surfaces of the masters. Using this nonlithographic approach, we fabricated microfluidic devices for detection of bacterial spores on the basis of enhancement of the emission of terbium (III) ions.

[The Influence of Promoter Methylation of RASSF1A on RASSF1A MRNA and Protein Expression in Gastric Cancer Tissues]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Dec, 2006  |  Pubmed ID: 17327001

To investigate RASSF1A expression in tissue of primary gastric cancer (GC) at mRNA and protein levels and analyze the relationship between DNA methylation status and RASSF1A expression in GC.

Arbitrary Optical Waveform Generation Using 2D Ring Resonator Arrays

Optics Express. Jul, 2006  |  Pubmed ID: 19516842

The direct temporal domain approach can be applied for arbitrary optical waveform generation using 2D ring resonator arrays (RRAs). To demonstrate the approach, we provide numerical examples which show the generation of two very different waveforms from the same input pulse. In particular, we consider a hyperbolic secant input pulse with 8 ps full width half maximum and generate (1) a 50 ps square-like waveform with 5 ps rising and falling times and a 40 ps flat-top as well as (2) a 60 ps triangular waveform with 30 ps rising and falling times, both with a 5x5 RRA. Simulations show that the generated waveforms are well-matched to their targets.

Prevalence and Risk Factors of Fatty Liver Disease in the Shuiguohu District of Wuhan City, Central China

Postgraduate Medical Journal. Mar, 2007  |  Pubmed ID: 17344575

Fatty liver disease (FLD) is highly prevalent in Western countries, but recent data have shown that FLD is also emerging in China.

Vascular and Cellular Stress in Inflammatory Bowel Disease: Revisiting the Role of Homocysteine

The American Journal of Gastroenterology. May, 2007  |  Pubmed ID: 17355415

Moderate hyperhomocysteinemia is a complex trait commonly associated with inflammatory bowel disease (IBD). Nutritional deficiencies and genetic determinants have been identified as risk factors for moderate hyperhomocysteinemia, such as folate and vitamin B(12) deprivation and polymorphisms in the 5,10 methylenetetrahydrofolate reductase (MTHFR) encoding gene, respectively. Homocysteine has a crucial role in cellular stress, epigenetic events, inflammatory processes, and host-microbial interactions. Hyperhomocysteinemia might therefore influence the clinical history of IBD, including disease severity, susceptibility to particular enteric infections, and the risk for the development of colorectal cancer. In contrast, homocysteine metabolism does not seem to contribute to the greater risk of thrombosis in IBD subjects. Herein, we review the evidence linking homocysteine metabolism to the pathophysiology of IBD. Furthermore, we discuss the relevance of screening and treating folate and vitamin B(12) deficiencies in IBD subjects. Given the peculiar frequency of such deficiencies in IBD, normalizing vitamin levels should be an integral part of the management of these patients, especially those with active disease, history of intestinal resection, and/or treated with methotrexate.

N-acetyltransferase 2 Slow Acetylator Genotype Associated with Adverse Effects of Sulphasalazine in the Treatment of Inflammatory Bowel Disease

Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. Mar, 2007  |  Pubmed ID: 17377643

N-acetyltransferase 2 (NAT2) is an important enzyme catalyzing N-acetylation of sulfasalazine (SASP). The aim of the present study was to investigate associations of the genotypes of NAT2 with inflammatory bowel disease (IBD), and with adverse effects of SASP, which is used as the first-line treatment of IBD.

Sinomenine Attenuates 2, 4, 6-trinitrobenzene Sulfonic Acid-induced Colitis in Mice

International Immunopharmacology. May, 2007  |  Pubmed ID: 17386408

Sinomenine is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum. It was demonstrated that sinomenine had anti-inflammatory and immunosuppressive effects in the previous studies. The aim of the present study was to evaluate therapeutic effects of sinomenine on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) induced colitis in mice. Two hours following colonic instillation of TNBS, sinomenine with several doses (30, 100, 200 mg/kg) was given by gastric gavage once daily for 7 days. Comparing with the saline-treated mice with TNBS-induced colitis, sinomenine (100 mg/kg and 200 mg/kg)-treated mice with TNBS-induced colitis were shown improvements of weight loss, macroscopic score, histological score, and myeloperoxidase activity. Moreover, treatments with sinomenine (100 mg/kg and 200 mg/kg) decreased the up-regulated mRNA and protein levels of tumour necrosis factor-alpha(TNF-alpha) and interferon-gamma (IFN-gamma) caused by TNBS. Our findings suggest that sinomenine attenuates TNBS-induced colitis in mice and the therapeutic mechanism might be related to the reduction of up-regulated colonic TNF-alpha and IFN-gamma production caused by TNBS.

Analysis of PALB2/FANCN-associated Breast Cancer Families

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2007  |  Pubmed ID: 17420451

No more than approximately 30% of hereditary breast cancer has been accounted for by mutations in known genes. Most of these genes, such as BRCA1, BRCA2, TP53, CHEK2, ATM, and FANCJ/BRIP1, function in DNA repair, raising the possibility that germ line mutations in other genes that contribute to this process also predispose to breast cancer. Given its close relationship with BRCA2, PALB2 was sequenced in affected probands from 68 BRCA1/BRCA2-negative breast cancer families of Ashkenazi Jewish, French Canadian, or mixed ethnic descent. The average BRCAPRO score was 0.58. A truncating mutation (229delT) was identified in one family with a strong history of breast cancer (seven breast cancers in three female mutation carriers). This mutation and its associated breast cancers were characterized with another recently reported but unstudied mutation (2521delA) that is also associated with a strong family history of breast cancer. There was no loss of heterozygosity in tumors with either mutation. Moreover, comparative genomic hybridization analysis showed major similarities to that of BRCA2 tumors but with some notable differences, especially loss of 18q, a change that was previously unknown in BRCA2 tumors and less common in sporadic breast cancer. This study supports recent observations that PALB2 mutations are present, albeit not frequently, in breast cancer families. The apparently high penetrance noted in this study suggests that at least some PALB2 mutations are associated with a substantially increased risk for the disease.

Risk Factors for Ulcerative Colitis in a Chinese Population: an Age-matched and Sex-matched Case-control Study

Journal of Clinical Gastroenterology. Mar, 2007  |  Pubmed ID: 17426467

Cigarette smoking, alcohol use, appendectomy, and family history of inflammatory bowel disease (IBD) have all been shown to be associated with IBD, but there were no reports of risk factors for IBD in a Chinese population in which the incidence of IBD is increasing during the past decade. We conducted a case-control study to examine associations between previously reported environmental risk factors and development of ulcerative colitis (UC) in Wuhan city, central China.

RAP80 Targets BRCA1 to Specific Ubiquitin Structures at DNA Damage Sites

Science (New York, N.Y.). May, 2007  |  Pubmed ID: 17525341

Mutations affecting the BRCT domains of the breast cancer-associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gammaH2AX-dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs.

Photoinduced Electron Transfer in Arylacridinium Conjugates in a Solid Glass Matrix

The Journal of Physical Chemistry. B. Jun, 2007  |  Pubmed ID: 17539680

The photophysical properties of a series of 9-arylacridinium conjugates in solid glass matrices composed of sucrose octaacetate have been determined. The fluorescence of the charge-shift states is significantly enhanced because of the retardation of nonradiative pathways for back-electron transfer. Changes of more than 3 orders of magnitude in back-electron-transfer rates (sucrose octaacetate glass vs conventional solvents at room temperature) were observed. Transient spectra displayed long-lived charge-shift species in the microsecond time regime for thianthrene acridinium conjugates. The rate retardation is associated with slow solvation times for surrounding solvent layers in the solid matrix. The red-edge effect (excitation wavelength-dependent fluorescence) for the arylacridinium ions in solid glass confirms the microheterogeneity of the sucrose octaacetate medium.

Type IVB Pilus Operon Promoter Controlling Expression of the Severe Acute Respiratory Syndrome-associated Coronavirus Nucleocapsid Gene in Salmonella Enterica Serovar Typhi Elicits Full Immune Response by Intranasal Vaccination

Clinical and Vaccine Immunology : CVI. Aug, 2007  |  Pubmed ID: 17596427

Attenuated Salmonella enterica serovar Typhi strains have been considered to be attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar Typhi strain stably expressing conserved nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) by integrating the N gene into the pilV gene, which was under the control of the type IVB pilus operon promoter in S. enterica serovar Typhi. BALB/c mice were immunized with this recombinant strain through different routes: intranasally, orogastrically, intraperitoneally, and intravenously. Results showed that the intranasal route caused the highest production of specific immunoglobulin G (IgG), IgG2a, and secretory IgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T-lymphocyte activities and increased gamma interferon-producing T cells compared with the parental strain. Our work provides insights into how the type IVB pilus operon promoter controlling SARS-CoV N gene expression in Salmonella might be attractive for a live-vector vaccine against SRAS-CoV infection, for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pilus operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.

Association of Diminished Expression of RASSF1A with Promoter Methylation in Primary Gastric Cancer from Patients of Central China

BMC Cancer. 2007  |  Pubmed ID: 17608924

Although methylation-mediated inactivation of expression of RASSF1A, a candidate tumor suppressor gene, has been observed in several human cancers, the data concerning alteration of RASSF1A expression and methylation in Chinese primary gastric cancer are scarce. Moreover, direct evidence showing the association between protein expression of RASSF1A and primary human cancers is lacking. The aim of this study was to investigate RASSF1A expression in tissue of primary gastric cancer (GC) at mRNA and protein levels, and to establish the possible relationship between DNA methylation status and protein expression of RASSF1A in Chinese.

Comparative Study on Treatment of Midshaft Tibial Fracture with Expandable and Interlocking Intramedullary Nails

Chinese Journal of Traumatology = Zhonghua Chuang Shang Za Zhi / Chinese Medical Association. Aug, 2007  |  Pubmed ID: 17651592

To evaluate the clinical results of treatment of midshaft tibial fracture with expandable intramedullary nails compared with interlocking intramedullary nails.

Deletion of N-glycosylation Sites of Hepatitis C Virus Envelope Protein E1 Enhances Specific Cellular and Humoral Immune Responses

Vaccine. Sep, 2007  |  Pubmed ID: 17675185

N-linked glycosylations of viral proteins have been implicated in immunogenicity. In this study, the effects of the N-linked glycosylation of the hepatitis C virus (HCV) E1 protein, a naturally poor immunogen, on the induction of specific immune response were examined. We constructed the plasmids containing the genes encoding both wild type and mutant E1 proteins in which N-linked glycosylation sites are mutated individually or in combination by site-directed mutagenesis. The immunogenicity of wild type E1 and six mutated E1 proteins was analyzed in BALB/C mice using a DNA-based vaccination approach. We found that E1-M2 mutant (at site of N209SS) significantly enhanced E1-specific CD8(+)T cells cytotoxic T lymphocytes (CTL) activities, expression of IFN-gamma producing T cells, and suppression of tumor growth. While E1-M4 mutant (at site of N305CS) induced the highest specific antibody response among all groups. Moreover, E1 wild-type vaccinated mice developed a mixture of IgG1 and Ig2a, but E1-M2 mutant induced only IgG2a isotype, and E1-M4 mutant dominantly developed IgG1 isotype. Our data showed that N-linked glycosylation can limit both cellular and antibody response to the HCV E1 protein and deletion of the N-glycosylation sites at N209SS and N305CS of hepatitis C virus envelope protein E1 provided potential applications for the development of DNA vaccine with enhanced immunogenicity.

Cadmium Tolerance and Accumulation by Two Species of Iris

Ecotoxicology (London, England). Nov, 2007  |  Pubmed ID: 17701346

Seedlings of Iris lactea var. chinensis (Fisch.) Koidz. and I. tectorum Maxim. were subjected to 0-160 mg l(-1) Cd in hydroponic system and harvested after 42 days to determine effects on root and shoot dry mass. A subset of 16-day-old seedlings was exposed to 1000 mg l(-1) Cd to characterize sub-cellular localization of Cd in root cells. The Cd contents in the shoots of I. lactea var. chinensis reached 529 microg g(-1 )dry weight (dw) at 80 mg l(-1) Cd treatment and in the shoots of I. tectorum reached 232 microg g(-1) dw at 40 mg l(-1) Cd treatment, without showing signs of visible toxicity. The Cd contents in the shoots of both two test species exceeded 100 microg g(-1), the critical value of Cd hyperaccumulator. The indices of tolerance (ITs) of I. lactea var. chinensis were higher than those of I. tectorum under 10-160 mg l(-1)Cd stress. Sub-cellular localization of Cd in root cells was evaluated using transmission electron microscopy (TEM) and Cd deposits were found in the cell walls, in the cytoplasm and on the inner surface of xylem vessels in the root tip of I. lactea var. chinensis and I. tectorum. A few cells in the root tip of I. tectorum were necrotic. The results showed that the tolerance and accumulation of Cd by I. lactea var. chinensis were higher than those of I. tectorum, suggesting that I. lactea var. chinensis has potential application in phytoremediation.

CCL19 and CXCL13 Synergistically Regulate Interaction Between B Cell Acute Lymphocytic Leukemia CD23+CD5+ B Cells and CD8+ T Cells

Journal of Immunology (Baltimore, Md. : 1950). Sep, 2007  |  Pubmed ID: 17709502

Interacting with T cells, cytokine-producing B cells play a critical protective role in autoimmune diseases. However, the interaction between malignant B and T cells remains to be fully elucidated. In a previous study, we have reported that ligation of CCL19-CCR7 and CXCL13-CXCR5 activates paternally expressed gene 10 (PEG10), resulting in an enhancement of apoptotic resistance in B-cell acute lymphocytic leukemia (B-ALL) CD23+CD5+ B cells. Here, we report that B-ALL CD23+CD5+ B cells produce IL-10 at high level, which can be further elevated by costimulation with CCL19 and CXCL13. CCL19/CXCL13-activated B-ALL CD23+CD5+ B cells, in turn, increase IL-10 expression in syngeneic CD8+ T cells in a B cell-derived IL-10-dependent manner and requiring a cell-cell contact. IL-10 secreted from B-ALL CD23+CD5+ B cells in vitro impairs tumor-specific CTL responses of syngeneic CD8+ T cells. The impairment of cytotoxicity of syngeneic CD8+ T cells is escalated by means of CCL19/CXCL13-induced up-regulation of IL-10 from B-ALL CD23+CD5+ B cells. Moreover, using a short hairpin RNA to knockdown PEG10, we provide direct evidence that increased expression of PEG10 in B-ALL CD23+CD5+ B cells is involved in malignant B-T cell interaction, contributing to the up-regulation of IL-10 expression, as well as to the impairment of cytotoxicity of syngeneic CD8+ T cells. Thus, malignant B-ALL CD23+CD5+ B cells play an immunoregulatory role in controlling different inflammatory cytokine expressions. IL-10 may be one of the critical cellular factors conferring B-ALL CD23+CD5+ B cells to escape from host immune surveillance.

[Selection of the Microorganism for Dioscin Hydrolyze]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Aug, 2007  |  Pubmed ID: 18074832

To select the microorganism which can hydrolyze dioscin to diosgenin.

Fanconi Anemia is Associated with a Defect in the BRCA2 Partner PALB2

Nature Genetics. Feb, 2007  |  Pubmed ID: 17200672

The Fanconi anemia and BRCA networks are considered interconnected, as BRCA2 gene defects have been discovered in individuals with Fanconi anemia subtype D1. Here we show that a defect in the BRCA2-interacting protein PALB2 is associated with Fanconi anemia in an individual with a new subtype. PALB2-deficient cells showed hypersensitivity to cross-linking agents and lacked chromatin-bound BRCA2; these defects were corrected upon ectopic expression of PALB2 or by spontaneous reversion.

Environmental Influence on the Worldwide Prevalence of a 776C->G Variant in the Transcobalamin Gene (TCN2)

Journal of Medical Genetics. Jun, 2007  |  Pubmed ID: 17220211

A 776C-->G variant (dbSNP ID: rs1801198) in the transcobalamin gene (TCN2; MIM# 275350) decreases the cellular and plasma concentration of transcobalamin and thereby influences the cellular availability of vitamin B(12).

A Recurrent Mutation in PALB2 in Finnish Cancer Families

Nature. Mar, 2007  |  Pubmed ID: 17287723

BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer. Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified. The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity. Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development.

Association Between Interleukin-1 Gene Polymorphisms and Helicobacter Pylori Infection in Gastric Carcinogenesis in a Chinese Population

Journal of Gastroenterology and Hepatology. Feb, 2007  |  Pubmed ID: 17295877

Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients.

Downregulation of Connexin 43 in Nasopharyngeal Carcinoma Cells is Related to Promoter Methylation

Oral Oncology. Oct, 2007  |  Pubmed ID: 17306607

Down-regulation of Cx43 expression had been shown to occur in nasopharyngeal carcinoma cells. The present study was undertaken to estimate if methylation of the promoter region in Cx43 gene was responsible for the repression of Cx43 expression in the CNE-1 nasopharyngeal carcinoma cells. Calcein transfer and lucifer yellow transfer were detected to evaluate gap junction intercellular communication (GJIC) in CNE-1 cells. It was found that the control CNE-1 cells showed no fluorescent dye transfer. After treatment with DNA methyltransferase inhibitor 5-aza-CdR, fluorescent dye transfer between cells became obvious. RT-PCR and Western blot were performed to determine the expression of Cx43 gene. The control CNE-1 cells showed a low expression level of Cx43, whereas 5-aza-CdR-treated CNE-1 cells showed an enhanced level of Cx43 expression. Methylation-sensitive restriction enzyme and PCR analysis showed that the methylation of the Cx43 gene promoter region occurred in CNE-1 cells. In addition, treatment with 5-aza-CdR inhibited the growth (including anchorage-independent growth) of CNE-1 cells, and resulted in an accumulation of cells in G0/G1 phase. These results indicate the promoter methylation as an important role in inactivation of Cx43 in CNE-1 cells.

[Chemical Constituents in the Root of Cynanchum Auriculatum]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Oct, 2007  |  Pubmed ID: 18300493

To study on the chemical constituents of root of Cynanchum auriculatum Royle ex Wight.

Penetrance Analysis of the PALB2 C.1592delT Founder Mutation

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Jul, 2008  |  Pubmed ID: 18628482

PALB2 is a recently identified breast cancer susceptibility gene. We have previously identified in the Finnish population a PALB2 c.1592delT founder truncation mutation that is associated with an increased risk of breast cancer. In the present study, we wanted to assess in more detail the increased risk (hazard ratio, HR) and the age-specific cumulative risk (penetrance) of c.1592delT with regard to susceptibility to breast and other forms of cancer.

CD19+CD5+ B Cells in Primary IgA Nephropathy

Journal of the American Society of Nephrology : JASN. Nov, 2008  |  Pubmed ID: 18650480

The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19(+)CD5(+) B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19(+)CD5(+) B cells did not change. CD19(+)CD5(+) B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-gamma, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19(+)CD5(+) B cells play a prominent role in the pathogenesis of primary IgA nephropathy.

Methionine Synthase A2756G Polymorphism May Predict Ulcerative Colitis and Methylenetetrahydrofolate Reductase C677T Pancolitis, in Central China

BMC Medical Genetics. 2008  |  Pubmed ID: 18700049

The association of genetic polymorphisms related to metabolism of homocysteine with inflammatory bowel disease has been evidenced in Crohn disease and remains an open question in ulcerative colitis. We evaluated the association of the polymorphisms of MTHFR, MTR, MTRR and TCN2 genes with ulcerative colitis in Central China.

Semi-permeable Nanocapsules of Konjac Glucomannan-chitosan for Enzyme Immobilization

International Journal of Pharmaceutics. Nov, 2008  |  Pubmed ID: 18725277

Carboxymethyl konjac glucomannan-chitosan (CKGM-CS) nanocapsules, spontaneously prepared under very mild conditions by electrostatic complexation, were used for immobilizing L-asparaginase. The matrix has semi-permeability to allow the substrate and product to pass through and to keep L-asparaginase in the matrix to prevent leaking. The cell-like hydrogel matrix was prepared in aqueous system without organic solvents and reagents. The process of the preparation does not denature the enzyme and the activity of the immobilized and native enzyme is very similar. The activity, stability, and characters of the enzyme-loaded nanocapsules were studied. The results indicated the immobilized enzyme has better stability and activity in contrast to the native enzyme. These studies may supply a new material for the immobilization of pH and temperature-sensitive enzyme.

[An Association Between MICB 0106 Allele and Ulcerative Colitis in Chinese Han in Hubei Province]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Mar, 2008  |  Pubmed ID: 18785505

To investigate the association between the exon 2, 3, 4 of MHC class I chain-related gene-B (MICB) and ulcerative colitis (UC) in Chinese Han.

[Genetic Variations in TrnL-F Sequence and Phylogenetic Clustering of Lycoris Species]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Jul, 2008  |  Pubmed ID: 18837305

To identify some closely related Lycoris species and evaluate interspecific relationships among them.

[Search for Fanconi Anemia/BRCA Pathway Defects in Lymphoma Cell Lines]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Oct, 2008  |  Pubmed ID: 18841560

To investigate the possible relationship between defects in the FA/BRCA pathway of genomic stability and potential pathogenesis of T and B cell lymphoma.

The Microenvironmental Determinants for Kidney Epithelial Cyst Morphogenesis

European Journal of Cell Biology. Apr, 2008  |  Pubmed ID: 18191498

Although epithelial morphogenesis is tightly controlled by intrinsic genetic programs, the microenvironment in which epithelial cells proliferate and differentiate also contributes to the morphogenetic process. The roles of the physical microenvironment in epithelial morphogenesis, however, have not been well dissected. In this study, we assessed the impact of the microenvironment on epithelial cyst formation, which often marks the beginning or end step of morphogenesis of epithelial tissues and the pathological characteristic of some diseases. Previous studies have demonstrated that Madin-Darby canine kidney (MDCK) epithelial cells form cysts when grown in a three-dimensional (3D) extracellullar matrix (ECM) environment. We have now further demonstrated that the presence of ECM in the 3D scaffold is required for the formation of properly polarized cysts. Also, we have found that the full interface of epithelial cells with the ECM environment (in-3D) is not essential for cyst formation, since partial contact (on-3D) is sufficient to induce cystogenesis. In addition, we have defined the minimal ECM environment or the physical threshold for cystogenesis under the on-3D condition. Only above the threshold can the morphological cues from the ECM environment induce cyst formation. Moreover, cyst formation under the on-3D condition described in this study defines a novel and more feasible model to analyze in vitro morphogenesis. Finally, we have found that, during cystogenesis, MDCK cells generate basal microprotrusions and produce vesicle-like structures to the basal extracellular space, which are specific to and correlated with cyst formation. For the first time, we have systematically and quantitatively elucidated the microenvironmental determinants for epithelial cystogenesis.

Defects of FA/BRCA Pathway in Lymphoma Cell Lines

International Journal of Hematology. Dec, 2008  |  Pubmed ID: 19011769

The aim was to find the possible relationship between defects in the FA/BRCA pathway of genomic maintenance and potential pathogenesis of T and B cell lymphoma. We screened 29 cell lines derived from diverse subtypes of lymphoma for possible FA pathway defects. The results indicated: no defect in FANCD2 ubiquitination, BRCA2 and FANCJ expression; absence of FANCN protein in three cell lines: HT, Sudhl4 and JEKO-1. This absence was correlated with enhanced MMC-induced G2 arrest, growth inhibition and high chromosomal breakage rate in the three cell lines. We only found one substitution in HT and JEKO-1 exon-5a fragment: c.1769C > T, p. A590V. But in another lymphoma cell line Sudhl4 with FANCN absence, we have not found any mutation. In conclusion, this mutation maybe the reason which caused FANCN protein expression absent or made the protein very unstable and lose its function in HT and JEKO-1 cell lines.

Functional Protection of Pentoxifylline Against Spinal Cord Ischemia/reperfusion Injury in Rabbits: Necrosis and Apoptosis Effects

Chinese Medical Journal. Dec, 2008  |  Pubmed ID: 19102966

Little is known about neuronal death mechanisms following spinal cord ischemia. The present study aimed to investigate the protective effect of pentoxifylline (PTX) against spinal cord ischemia/reperfusion (I/R) injury.

[Studies on Chemical Constituents from Zephyranthes Candida]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Oct, 2008  |  Pubmed ID: 19230401

To study on the chemical constituents of Zephyranthes candida.

Long-lived Photogenerated States of Alpha-oligothiophene-acridinium Dyads Have Triplet Character

The Journal of Physical Chemistry. A. Apr, 2009  |  Pubmed ID: 19267468

Photoinduced processes, leading to charge-transfer states with extended lifetimes, are of key importance for solar-energy-conversion applications. Utilizing external heavy-atom effect allowed us to photogenerate long-lived transients of electron donor-acceptor dyads. For an electron acceptor and a principal chromophore of the dyads, we selected N-methylacridinium, and for electron donors thiophene, bithiophene, and terthiophene were selected. While the photoinduced charge transfer, mediated by the investigated dyads, occurred in the picosecond time domain, the lifetime of the transients extended to the microsecond time domain. We ascribed the relatively long lifetimes to the triplet character of the observed transients. An increase in the size of the donor lowered the energy of the charge-transfer states of the dyads. When the energy level of the acridinium triplet lies below the energy level of the charge-transfer state, the locally excited triplet accounted for the long-lived transient. For the conjugates with charge-transfer states lying below all other excited states, the long-lived transients were, indeed, the charge-transfer species.

PALB2 Links BRCA1 and BRCA2 in the DNA-damage Response

Current Biology : CB. Mar, 2009  |  Pubmed ID: 19268590

BRCA1 and BRCA2 are often mutated in familial breast and ovarian cancer. Both tumor suppressors play key roles in the DNA-damage response. However, it remains unclear whether these two tumor suppressor function together in the same DNA-damage response pathway. Here, we show that BRCA1 associates with BRCA2 through PALB2/FANCN, a major binding partner of BRCA2. The interaction between BRCA1 and BRCA2 is abrogated in PALB2-deficient Fanconi anemia cells and in the cells depleted of PALB2 by small interfering RNA. Moreover, we show that BRCA1 promotes the concentration of PALB2 and BRCA2 at DNA-damage sites and the interaction between BRCA1 and PALB2 is important for the homologous recombination repair. Taken together, our results indicate that BRCA1 is an upstream regulator of BRCA2 in the DNA-damage response, and PALB2 is the linker between BRCA1 and BRCA2.

Cloning and Heterologous Expression of a New 3'-hydroxylase Gene from Lycoris Radiata

Zeitschrift Für Naturforschung. C, Journal of Biosciences. Jan-Feb, 2009  |  Pubmed ID: 19323279

A full-length cDNA (LC3'H) was obtained from a cDNA library of Lycoris radiata by DOP-PCR (degenerate oligonucleotide primer PCR), 3'race and 5'race methods. Compared with the other reported enzymes from different plants, the deduced amino acid sequence of LC3'H exhibits significant homologies to 3'-hydroxylases that are involved in the caffeic acid biosynthesis. These findings suggest that the new gene is closely related to the biosynthesis of caffeic acid, which is also an important step of the galanthamine biosynthesis in Amaryllidaceae plants.

Can Pancreatic Duct-derived Progenitors Be a Source of Islet Regeneration?

Biochemical and Biophysical Research Communications. Jun, 2009  |  Pubmed ID: 19324022

The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing beta-cells. The functional mass of beta-cells is decreased in type 1 diabetes, so replacing missing beta-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the beta-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding beta-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet beta-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the "gold standard" of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as an in vivo progenitor for pancreatic beta-cells has implications for a potentially important, expandable source of new islets for diabetic replenishment therapy.

[Treatment of Humeral Shaft Fractures with Retrograde Expandable Intramedullary Nailing System]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Apr, 2009  |  Pubmed ID: 19408773

[Patch Diversity and Spatial Structure of Wild Thymus Quinquecostatus]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Jan, 2009  |  Pubmed ID: 19449560

With the combination of ISSR (inter-simple sequence repeats), SRAP (sequence-related amplified polymorphism) and spatial autocorrelation, the genetic diversity and spatial structure per unit patch of three Huaiyuan populations of Thymus quinquecostatus in southeast China were analyzed. The results showed that there existed higher levels of genetic and clonal diversity among the patches within the wild T. quinquecostatus populations, with the percentage of polymorphic loc being 75.75%, Nei's gene diversity being 0.2537, Shannon's information index being 0.3811, percent of genetype (G/N) being 0.61, Simpson index (D) being 0.96, and Fager index (E) being 0.91. Analysis of molecular variance (AMOVA) showed that only 9.65% of genetic variation resided among the populations, while 90.35% of it resided among the individuals within the populations. No genotype patches in common were observed among the three populations. The spatial distribution of the same patches showed a concentrated distribution about 0-25 m, and that of different patches showed an inlaid distribution. Except for some locations that showed par correlations in the Huaiyuan populations of T. quinquecostatus, most locations lacked in spatial structure according to spatial autocorrelation analysis. The possible mechanism causing the establishment of the patches of T. quinquecostatus populations was due to seed dispersing, and the following clonal reproduction played important roles in patch development and population expanding.

Role of Major Histocompatibility Complex Class I-related Molecules A*A5.1 Allele in Ulcerative Colitis in Chinese Patients

Immunology. Sep, 2009  |  Pubmed ID: 19016911

The major histocompatibility complex (MHC) class I-related molecules A (MICA) is a stress-inducible cell surface antigen that is recognized by intestinal epithelial Vdelta1 gammadelta T cells, natural killer (NK) cells and CD8(+) T cells with NKG2D receptor participating in the immunological reaction in the intestinal mucosa. The present study aimed to investigate the functions of the MICA*A5.1 allele in the development of ulcerative colitis (UC) in the Chinese population. The microsatellite polymorphisms of MICA were genotyped in 124 unrelated Chinese patients with UC and 172 ethnically matched healthy controls using a semiautomatic fluorescently labelled polymerase chain reaction. MICA*A5.1-expressing Raji cells were generated by gene transfection. Cytotoxicity of NK cells to Raji cells expressing different MICA molecules was detected using the lactate dehydrogenase method. Soluble MICA in the culture supernatant was detected by enzyme-linked immunosorbent assay. The frequency of MICA*A5.1 was significantly higher in UC patients compared with the healthy controls (29.0% versus 17.4%, P = 0.001, corrected P = 0.005, OR = 1.936, 95% CI 1.310-2.863) and the frequency of a MICA*A5.1/A5.1 homozygous genotype was increased in UC patients (18.5% versus 7% in healthy controls, P = 0.0032, corrected P = 0.048, OR = 3.036, 95% CI 1.447-6.372). Raji cells with MICA*A5.1 expression produced more soluble MICA (t = 5.75, P < 0.01) than Raji cells with full-length MICA expression in culture supernatant. Raji cells with MICA*A5.1 expression were more resistant to killing by NK cells than Raji cells with full-length MICA expression. The MICA*A5.1 allele and MICA*A5.1/A5.1 genotype are significantly associated with Chinese UC patients in central China. MICA*A5.1 may play a role in the development of UC by producing more soluble MICA and resistance to NK cells.

Cytotoxic T Lymphocyte Antigen-4 Promoter -658CT Gene Polymorphism is Associated with Ulcerative Colitis in Chinese Patients

International Journal of Colorectal Disease. May, 2009  |  Pubmed ID: 19089435

Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a role in the downregulation of T cell activation. The present study aimed to examine an association between the CTLA-4 gene polymorphisms and ulcerative colitis (UC) in the Han Chinese in central China.

Two Novel Ceramides with a Phytosphingolipid and a Tertiary Amide Structure from Zephyranthes Candida

Lipids. Jan, 2009  |  Pubmed ID: 18941821

Two novel ceramides, Candidamide A (1) with a phytosphingolipid structure, and Candidamide B (2) with a tertiary amide structure, together with 12 known compounds (3-14) have been isolated from the bulbs of Zephyranthes candida, The structures of 1 and 2 have been elucidated to be 1,3,5,6-tetrahydroxy-2-(2'-hydroxytetracosanoyl amino)-8-(E)-octadecadiene (1) and (2S,3S,4R,8E,2'R)-2-[N-(2'-hydroxyoctadecanoyl)-N-(1'',2''-dihydroxyethyl)-amino]-8-hexacosene-1,3,4-triol (2) on the basis of spectroscopic evidence including IR, MS, NMR ((1)H-NMR, (13)C-NMR, DEPT, (1)H-(1)H COSY, HSQC, HMBC). The known compounds were identified as (2S)-3',7-dihydroxy-4'-methoxyflavan (3), (2S)-4'-hydroxy-7-methoxyflavan (4), (2S)-4',7-dihydroxyflavan (5), 7-hydroxy-3', 4'-methylenedioxyflavan (6), ambrettolide (7), beta-sitostero1 (8), beta-daucosterin (9), rutin (10), pancratistatin (11), lycorine (12), haemanthidine (13), and haemanthamine (14). In the antimicrobial assay, candidamide A (1) and candidamide B (2) displayed moderate activities against bacteria Staphylococcus aureus and Escherichia coli, and fungi Aspergillus niger, Candida albicans and Trichophyton rubrum.

Possible Therapeutic Effect of a Traditional Chinese Medicine, Sinisan, on Chronic Restraint Stress Related Disorders

Neuroscience Letters. Jan, 2009  |  Pubmed ID: 19007859

According to Traditional Chinese Medicine (TCM), the liver is the origin or most associated with stress related disorders such as depression. Sinisan, a TCM prescription, has been used as a hepatic protectant. We examined whether Sinisan exerts therapeutic effects in an experimental animal model: the chronic restraint stress (CRS) model. Sinisan was administered in the animal's drinking water at a concentration of 100mg/kg for 21 days (7 days pre-CRS and 14 days during the CRS). Spatial learning and memory were measured 24h after the CRS procedures using the Morris Water Maze (MWM). Aggressive behavior and body weight were determined as well. The Sinisan treatment decreased aggressive behaviors and reversed CRS-induced impairment of spatial learning and memory as well as decreased rate of growth. In conclusion, our results suggest that Sinisan does exert measurable therapeutic effects in an experimental chronic stress model.

[Association of IL-10 Gene Polymorphisms with Gastroduodenal Diseases in Hubei Han Population]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Aug, 2009  |  Pubmed ID: 20017308

To study the distribution of IL-10 gene polymorphisms in patients with gastroduodenal diseases in Hubei Han population and their association with helicobacter pylori (Hp) infection.

[Association of Cytotoxic T Lymphocyte Antigen-4 Promoter C-658T Polymorphism with Ulcerative Colitis in Chinese]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Aug, 2009  |  Pubmed ID: 20017310

To investigate the association of gene polymorphism of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) with ulcerative colitis (UC) in Chinese.

Recruitment of Fanconi Anemia and Breast Cancer Proteins to DNA Damage Sites is Differentially Governed by Replication

Molecular Cell. Sep, 2009  |  Pubmed ID: 19748364

Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remain unclear. We developed a chromatin-IP-based strategy termed eChIP and detected association of multiple FA proteins with DNA crosslinks in vivo. Interdependence analyses revealed that crosslink-specific enrichment of various FA proteins is controlled by distinct mechanisms. BRCA-related FA proteins (BRCA2, FANCJ/BACH1, and FANCN/PALB2), but not FA core and I/D2 complexes, require replication for their crosslink association. FANCD2, but not FANCJ and FANCN, requires the FA core complex for its recruitment. FA core complex requires nucleotide excision repair proteins XPA and XPC for its association. Consistent with the distinct recruitment mechanism, recombination-independent crosslink repair was inversely affected in cells deficient of FANC-core versus BRCA-related FA proteins. Thus, FA proteins participate in distinct DNA damage response mechanisms governed by DNA replication status.

Effect of Abiotic and Biotic Elicitors on Growth and Alkaloid Accumulation of Lycoris Chinensis Seedlings

Zeitschrift Für Naturforschung. C, Journal of Biosciences. Jul-Aug, 2009  |  Pubmed ID: 19791507

Three-month-old seedlings of Lycoris chinensis were treated with biotic and abiotic elicitors: yeast elicitor (YE), methyl jasmonate (MJ), salicylic acid (SA), and sodium nitroprusside as NO donator (NO). We have shown that the addition of MJ and NO promotes the accumulation of galanthamine in these seedlings. The effect of these elicitors on the growth of the seedlings, as well as on the amount of the alkaloids accumulated in the seedlings was studied. The results showed that, in general, high doses of MJ and SA had a negative effect on the growth of the seedlings, while appropriate doses of NO and YE had a positive effect on the growth of the seedlings. It was remarkable that the addition of MJ, NO, and YE can promote galanthamine accumulation in seedlings. The accumulation was higher in treatments at higher concentrations of NO (100 microM), where the release of galanthamine was 1.72-fold higher than that of the control at the 10th day of culture. The highest values of lycorine were obtained in seedlings treated with YE at a concentration of 0.01 g/l and by the 10th day of culture; the level was 1.38 times of the control.

A New Triterpene from the Fruiting Bodies of Ganoderma Lucidum

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Jul, 2009  |  Pubmed ID: 19806918

A new lanostanoid triterpene, named ganoderitriol M (1), together with a known triterpene ganoderic acid epsilon (2), were isolated from the fruiting bodies of G lucidum. Compound 1 was deduced as (24S)-lanosta-7-oxo-8-en-3beta, 24, 25-triol on the basis of spectral analysis (UV, IR, MS, 1H NMR, 13C NMR and 2D NMR).

Inferior Alveolar Canal Course: a Radiographic Study

Clinical Oral Implants Research. Nov, 2009  |  Pubmed ID: 19719735

To describe the morphology and course of the inferior alveolar canal (IAC) as it appears in digital panoramic radiographs.

[The Relationship Among IL-10, TNF Gene Polymorphisms, Helicobacter Pylori Infection and Gastroduodenal Diseases in Hubei Han Ethnic]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Jul, 2009  |  Pubmed ID: 19957794

To study the distribution of IL-10 and TNF gene polymorphisms in patients with gastroduodenal diseases in Hubei Han ethnic and their association with Helicobacter pylori (Hp) infection.

In Vivo Hypoglycemic Effects of Phenolics from the Root Bark of Morus Alba

Fitoterapia. Dec, 2009  |  Pubmed ID: 19545615

Moracin M (1), Steppogenin-4'-O-beta-D-glucosiade (2), Mullberroside A (3) were isolated from the root bark of Morus alba L. and identified by spectral evidence. Compounds 1, 2 and 3 were studied in hypoglycemic effects on alloxan-diabetic mice. The results showed that compounds 1, 2 and 3 all produced hypoglycemic effects. The compound 2 in a dose of 50 mg/kg exerted significant effect (p<0.05), 2 and 3 in a dose of 100 mg/kg exerted obviously effect (p<0.01). Meantime, the compound 1 in a dose of 100 mg/kg can make the fasting blood glucose level have decreasing tendency.

A New Class of Potent Matrix Metalloproteinase 13 Inhibitors for Potential Treatment of Osteoarthritis: Evidence of Histologic and Clinical Efficacy Without Musculoskeletal Toxicity in Rat Models

Arthritis and Rheumatism. Jul, 2009  |  Pubmed ID: 19565489

Matrix metalloproteinases (MMPs) have long been considered excellent targets for osteoarthritis (OA) treatment. However, clinical utility of broad-spectrum MMP inhibitors developed for this purpose has been restricted by dose-limiting musculoskeletal side effects observed in humans. This study was undertaken to identify a new class of potent and selective MMP-13 inhibitors that would provide histologic and clinical efficacy without musculoskeletal toxicity.

Genetic Polymorphism of Methylenetetrahydrofolate Reductase G1793A, Hyperhomocysteinemia, and Folate Deficiency Correlate with Ulcerative Colitis in Central China

Journal of Gastroenterology and Hepatology. Jun, 2010  |  Pubmed ID: 20594233

Methylenetetrahydrofolate reductase (MTHFR) encoding genes were associated with ulcerative colitis in Chinese in our previous study. We further studied association of a new polymorphism of MTHFR G1793A with ulcerative colitis and assessed relationship of this polymorphism with hyperhomocysteinemia (HHcy, > or = 15 mmol/L) and deficiency of folate (< or = 7 nmol/L) and vitamin B(12) (< or = 150 pmol/L) in a cohort of patients with ulcerative colitis in central China.

[Probiotic Therapy Using Live Combined Bifidobacterium, Lactobacillus and Enterococcus for Experimental Colitis in Rats Model]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. May, 2010  |  Pubmed ID: 20646418

To evaluate the effect of live combined bifidobacterium, lactobacillus and enterococcus capsules for colitis in rats induced by trinitrobenzenesulfonic acid (TNBS), so as to explore a new therapy for inflammatory bowel diseases (IBD).

A New Pathogenesis-related Protein, LrPR4, from Lycoris Radiata, and Its Antifungal Activity Against Magnaporthe Grisea

Molecular Biology Reports. Feb, 2010  |  Pubmed ID: 19728144

A new Lycoris radiata pathogenesis-related (PR)-4 gene, LrPR4 was isolated. LrPR4 encodes a 142 amino acid protein with a predicted molecular mass of 15.43 kDa and pI of 7.56. The putative LrPR4 shows high similarity to PR4 type proteins from various plant species and belongs to the Barwin family. Like other PR4s from monocot plants, LrPR4 protein contains a conserved Barwin domain and has a signal peptide at its N-terminus. The recombinant LrPR4 protein expressed in Escherichia coli showed activity towards hydrolysing RNA from L. radiata bulbs and antifungal activity. The results of this study suggest that LrPR4 may play a role in the disease resistance responses of plant against pathogen attacks though its antifungal activity.

Disease-related Expression of the IL6/STAT3/SOCS3 Signalling Pathway in Ulcerative Colitis and Ulcerative Colitis-related Carcinogenesis

Gut. Feb, 2010  |  Pubmed ID: 19926618

Mouse models have shown that interleukin (IL)6 stimulates survival, proliferation and progression to cancer of intestinal epithelial cells via activation of signal transducers and activators of transcription 3 (STAT3).

[CTLA-4 Gene Polymorphism Regulates CTLA-4 MRNA Stability and Protein Level in Patients with Ulcerative Colitis]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Dec, 2010  |  Pubmed ID: 21154316

To investigate the effect of (AT)n repeat polymorphism of the 3'untranslated region in cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene on CTLA-4 mRNA stability and full length (flCTLA-4) and soluble CTLA4 (sCTLA-4) expression in ulcerative colitis (UC).

MICB0106 Gene Polymorphism is Associated with Ulcerative Colitis in Central China

International Journal of Colorectal Disease. Feb, 2010  |  Pubmed ID: 19662431

The highly polymorphic nonclassical MHC class I chain-related genes A and B (MICA and MICB) encode stress-inducible glycoproteins expressed on various epithelial cells including intestinal epithelial cells. MICA and MICB gene polymorphisms and expressions are associated with autoimmune diseases but not known in ulcerative colitis (UC).

Distribution of Peroxisome Proliferator-activated Receptor-gamma Polymorphisms in Chinese and Dutch Patients with Inflammatory Bowel Disease

Inflammatory Bowel Diseases. Feb, 2010  |  Pubmed ID: 19714744

As peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is frequently expressed in colon, its genetic polymorphism may play a role in the etiology of inflammatory bowel disease (IBD). The aims of the present study were to determine the distribution of PPAR-gamma polymorphisms Pro12Ala and C161T and to explore the association between the PPAR-gamma genotypes and phenotypes of IBD patients.

Impaired PI3K/Akt Signal Pathway and Hepatocellular Injury in High-fat Fed Rats

World Journal of Gastroenterology : WJG. Dec, 2010  |  Pubmed ID: 21182226

to determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt, also known as PKB) pathway.

Removal of Copper from Aqueous Solution by Carbon Nanotube/calcium Alginate Composites

Journal of Hazardous Materials. May, 2010  |  Pubmed ID: 20083351

With bulk production and increasing application of carbon nanotubes (CNTs) as adsorbents in wastewater treatment, they will eventually be discharged into water environment and result in human contact risk to these toxic materials. However, so far few attentions have been paid to resolve the environmental micro-pollution caused by these micro-sized CNTs. In this research, an environmental friendly adsorbent, CNTs immobilized by calcium alginate (CNTs/CA) was prepared. Its copper adsorption properties were investigated via equilibrium studies. Experimental results showed that copper removal efficiency of CNTs/CA is high and reaches 69.9% even at a lower pH of 2.1. The copper adsorption capacity of CNTs/CA can attain 67.9 mg/g at copper equilibrium concentration of 5mg/L.

Mirid Bug Outbreaks in Multiple Crops Correlated with Wide-scale Adoption of Bt Cotton in China

Science (New York, N.Y.). May, 2010  |  Pubmed ID: 20466880

Long-term ecological effects of transgenic Bacillus thuringiensis (Bt) crops on nontarget pests have received limited attention, more so in diverse small holder-based cropping systems of the developing world. Field trials conducted over 10 years in northern China show that mirid bugs (Heteroptera: Miridae) have progressively increased population sizes and acquired pest status in cotton and multiple other crops, in association with a regional increase in Bt cotton adoption. More specifically, our analyses show that Bt cotton has become a source of mirid bugs and that their population increases are related to drops in insecticide use in this crop. Hence, alterations of pest management regimes in Bt cotton could be responsible for the appearance and subsequent spread of nontarget pests at an agro-landscape level.

The Prevalence and Diagnostic Value of Perinuclear Antineutrophil Cytoplasmic Antibodies and Anti-Saccharomyces Cerevisiae Antibodies in Patients with Inflammatory Bowel Disease in Mainland China

Clinica Chimica Acta; International Journal of Clinical Chemistry. Oct, 2010  |  Pubmed ID: 20570669

Perinuclear anti-neutrophil cytoplasmic (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have been studied extensively in Western countries. We determined the prevalence of pANCA and ASCA in the mainland Chinese population and the ability of pANCA and ASCA to discriminate between ulcerative colitis (UC) and Crohn's disease (CD).

Alkaloid Accumulation in Different Parts and Ages of Lycoris Chinensis

Zeitschrift Für Naturforschung. C, Journal of Biosciences. Jul-Aug, 2010  |  Pubmed ID: 20737914

The galanthamine, lycorine, and lycoramine content of Lycoris chinensis was researched during development from young to old plants, i.e. in seeds, ten-day-old seedlings, three-month-old seedlings, one-year-old seedlings, and perennial seedlings. Notably the alkaloid level reduced to its lowest content 10 days after seed germinating. Then the accumulation of galanthamine tended to increase with age, reaching a higher value in perennial seedlings. The production pattern of lycorine and lycoramine was found similar to that of galanthamine. Different plant organs were also evaluated for their galanthamine, lycorine, and lycoramine contents. Mature seeds had the highest content of galanthamine (671.33 microg/g DW). Kernels, seed capsules, and root-hairs were the main repository sites for galanthamine, lycorine, and lycoramine. The leaves were the least productive organs.

PALB2/FANCN: Recombining Cancer and Fanconi Anemia

Cancer Research. Oct, 2010  |  Pubmed ID: 20858716

Partner and localizer of BRCA2 (PALB2) was originally identified as a BRCA2-interacting protein that is crucial for key BRCA2 genome caretaker functions. It subsequently became clear that PALB2 was another Fanconi anemia (FA) gene (FANCN), and that monoallelic PALB2 mutations are associated with increased risk of breast and pancreatic cancer. Mutations in PALB2 have been identified in breast cancer families worldwide, and recent studies have shown that PALB2 also interacts with BRCA1. Here, we summarize the molecular functions and clinical phenotypes of this key DNA repair pathway component and discuss how its discovery has advanced our knowledge of both FA and adult cancer predisposition.

Cooperation of Breast Cancer Proteins PALB2 and Piccolo BRCA2 in Stimulating Homologous Recombination

Nature Structural & Molecular Biology. Oct, 2010  |  Pubmed ID: 20871615

Inherited mutations in human PALB2 are associated with a predisposition to breast and pancreatic cancers. PALB2's tumor-suppressing effect is thought to be based on its ability to facilitate BRCA2's function in homologous recombination. However, the biochemical properties of PALB2 are unknown. Here we show that human PALB2 binds DNA, preferentially D-loop structures, and directly interacts with the RAD51 recombinase to stimulate strand invasion, a vital step of homologous recombination. This stimulation occurs through reinforcing biochemical mechanisms, as PALB2 alleviates inhibition by RPA and stabilizes the RAD51 filament. Moreover, PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion. Finally, we show that PALB2-deficient cells are sensitive to PARP inhibitors. Our studies provide the first biochemical insights into PALB2's function with piBRCA2 as a mediator of homologous recombination in DNA double-strand break repair.

[The Relationship of Methylenetetrahydrofolate Reductase G1793A Gene Polymorphism, Hyperhomocysteinaemia and Ulcerative Colitis]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Aug, 2010  |  Pubmed ID: 20979787

The present study aimed to investigate the associations between genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) G1793A, plasma homocysteine (Hcy) levels, vitamin status and ulcerative colitis (UC) in a cohort of patients in Hubei Han nationality.

[Application Value of FS-3D-FISP Sequence in the Diagnosis of Ankle Cartilage Injury]

Zhonghua Yi Xue Za Zhi. Jul, 2010  |  Pubmed ID: 20979892

To compare several sequences of MRI and arthroscopy for detecting the ankle articular cartilage lesions and to evaluate the clinical outcome of special sequence of FS-3D-FISP.

Effect of Cytotoxic T Lymphocyte-associated Molecule 4 1661 Gene Polymorphism on Its Expression and Transcription in Ulcerative Colitis

Journal of Digestive Diseases. Dec, 2010  |  Pubmed ID: 21091900

Our aim was to investigate the expression of cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) in ulcerative colitis (UC) and to evaluate the effect of CTLA-4 gene -1661A/G polymorphism on CTLA-4 expression and transcription.

Effective Inhibition of Replication of Infectious Bursal Disease Virus by MiRNAs Delivered by Vectors and Targeting the VP2 Gene

Journal of Virological Methods. May, 2010  |  Pubmed ID: 19189848

RNA interference (RNAi) is a potent mechanism against a variety of viral infections. Infectious bursal disease virus (IBDV) causes an important disease economically in chickens, which is difficult to control. As part of the development of viral vector-mediated RNAi strategy against the disease, five anti-VP2 small interference RNAs were selected for construction of microRNA (miRNA) expression vectors tailored for avian cells. Transfection of DF-1 cells with the five vectors resulted in significant inhibition of VP2-EGFP reporter gene expression. More effective miVP2A and miVP2E were selected for further study using single or double miRNA expression vectors. After demonstration of specific miRNA expression, the gene silencing effects were determined in the vector-transfected and IBDV-infected cells. Reverse transcriptase PCR and virus titration showed inhibition rates from 76 to 82% on VP2 expression and significant decreases in virus titer by individual and co-expressed miVP2A and miVP2E. The inhibitory effects lasted for at least 120 h after infection with IBDV. These data suggest that the miRNAs targeting the VP2 can inhibit efficiently replication of IBDV.

Oncogenic RAS Regulates BRIP1 Expression to Induce Dissociation of BRCA1 from Chromatin, Inhibit DNA Repair, and Promote Senescence

Developmental Cell. Dec, 2011  |  Pubmed ID: 22137763

Here, we report a cell-intrinsic mechanism by which oncogenic RAS promotes senescence while predisposing cells to senescence bypass by allowing for secondary hits. We show that oncogenic RAS inactivates the BRCA1 DNA repair complex by dissociating BRCA1 from chromatin. This event precedes senescence-associated cell cycle exit and coincides with the accumulation of DNA damage. Downregulation of BRIP1, a physiological partner of BRCA1 in the DNA repair pathway, triggers BRCA1 chromatin dissociation. Conversely, ectopic BRIP1 rescues BRCA1 chromatin dissociation and suppresses RAS-induced senescence and the DNA damage response. Significantly, cells undergoing senescence do not exhibit a BRCA1-dependent DNA repair response when exposed to DNA damage. Overall, our study provides a molecular basis by which oncogenic RAS promotes senescence. Because DNA damage has the potential to produce additional "hits" that promote senescence bypass, our findings may also suggest one way a small minority of cells might bypass senescence and contribute to cancer development.

Treating TNBS-induced Colitis in Rats with Probiotics

The Turkish Journal of Gastroenterology : the Official Journal of Turkish Society of Gastroenterology. Oct, 2011  |  Pubmed ID: 22234755

We aimed to investigate the therapeutic effects of Peifeikang, a probiotics compound, on colitis in rats induced by trinitrobenzene sulfonic acid and to elucidate its potential mechanism.

Upregulated MRNA Expression of Major Histocompatibility Complex Class I Chain-related Gene A in Colon and Activated Natural Killer Cells of Chinese Patients with Ulcerative Colitis

Journal of Digestive Diseases. Apr, 2011  |  Pubmed ID: 21091928

To explore the expression of major histocompatibility complex class I chain-related gene A (MICA) and its ligand in colonic mucosa and the role of MICA-natural killer (NK) group 2D (NKG2D) interaction in activating NK cells in ulcerative colitis (UC) patients.

Effects of Recombinant Human Intestinal Trefoil Factor on Trinitrobenzene Sulphonic Acid Induced Colitis in Rats

Molecular Biology Reports. Oct, 2011  |  Pubmed ID: 21153768

Intestinal trefoil factor (ITF) has been proved to be effective in treatment of ulcerative colitis. However, the mechanisms of it remain unclear. In this study, we observed the effects of combined treatment with 5-aminosalicylic acid (5-ASA) and recombinant human ITF (rhITF) on the expression of Myeloperoxidase (MPO), nuclear factor-κB (NF-κB) and epidermal growth factor (EGF) in trinitrobenzene sulphonic acid (TNBS) induced colitis in rats. Forty Sprague-Dawley (SD) male rats which were induced to distal colitis by the colonic administration of TNBS, were randomly divided into four groups and colonically treated with normal saline (A), 5-ASA (B), rhITF (C), respectively. The macroscopic and histological changes of the colon, activities of MPO, expressions of serum EGF and tissue NF-κB were detected. The results showed that manifestation, colonic damage score and MPO activities of the rats treated with 5-ASA or/and rhITFs were improved, serum EGF production was augmented and expression of tissue NF-κB was down-regulated. Single usage of 5-ASA or rhITF had no significant difference, but combined using of them had more significant and noticeable effects compared to any single treatment. It could be concluded that topical treatment with 5-ASA and rhITF had beneficial effects in treating TNBS-induced colitis of rats and combined treatment was better than single treatment. It was possibly related to suppression of neutrophil infiltration, down-regulation expression of NF-κB and up-regulation expression of EGF.

Methyl Deficient Diet Aggravates Experimental Colitis in Rats

Journal of Cellular and Molecular Medicine. Nov, 2011  |  Pubmed ID: 21199330

Inflammatory bowel diseases (IBD) result from complex interactions between environmental and genetic factors. Low blood levels of vitamin B12 and folate and genetic variants of related target enzymes are associated with IBD risk, in population studies. To investigate the underlying mechanisms, we evaluated the effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an experimental model of colitis induced by dextran sodium sulphate (DSS), in rat pups from dams subjected to the MDD during gestation and lactation. Four groups were considered (n = 12-16 per group): C DSS(-) (control/DSS(-)), D DSS(-) (deficient/DSS(-)), C DSS(+) (control/DSS(+)) and D DSS(+) (deficient/DSS(+)). Changes in apoptosis, oxidant stress and pro-inflammatory pathways were studied within colonic mucosa. In rat pups, the MDD produced a decreased plasma concentration of vitamin B12 and folate and an increased homocysteine (7.8 ± 0.9 versus 22.6 ± 1.2 μmol/l, P < 0.001). The DSS-induced colitis was dramatically more severe in the D DSS(+) group compared with each other group, with no change in superoxide dismutase and glutathione peroxidase activity, but decreased expression of caspase-3 and Bax, and increased Bcl-2 levels. The mRNA levels of tumour necrosis factor (TNF)-α and protein levels of p38, cytosolic phospolipase A2 and cyclooxygenase 2 were significantly increased in the D DSS(+) pups and were accompanied by a decrease in the protein level of tissue inhibitor of metalloproteinases (TIMP)3, a negative regulator of TNF-α. MDD may cause an overexpression of pro-inflammatory pathways, indicating an aggravating effect of folate and/or vitamin B12 deficiency in experimental IBD. These findings suggest paying attention to vitamin B12 and folate deficits, frequently reported in IBD patients.

Association of Cytotoxic T Lymphocyte Associated Antigen-4 Gene (rs60872763) Polymorphism with Crohn's Disease and High Levels of Serum SCTLA-4 in Crohn's Disease

Journal of Gastroenterology and Hepatology. May, 2011  |  Pubmed ID: 21251066

Our aim was to evaluate cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphisms in Crohn's disease (CD) and explore soluble CTLA-4 (sCTLA-4) levels in serum of CD patients in central China.

Cryptococcus Neoformans Infection in Ulcerative Colitis with Immunosuppressants

Inflammatory Bowel Diseases. Sep, 2011  |  Pubmed ID: 21287669

Biomarker-based Prediction of Inflammatory Bowel Disease-related Colorectal Cancer: a Case-control Study

Cellular Oncology (Dordrecht). Apr, 2011  |  Pubmed ID: 21327897

Regular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy.

Apoptosis and Membrane Permeabilisation Induced by Macranthoside B on HL-60 Cells

Natural Product Research. Feb, 2011  |  Pubmed ID: 21328130

Triterpene saponins are throught to be potential anti-tumour agents in many cell types. This study aims to evaluate the cytotoxic activity and mechanism of a triterpene saponin, macranthoside B (MB), isolated from Lonicera macranthoides Hand.-Mazz. (Caprifoliaceae). A cell viability assay showed that MB inhibited cell growth of a panel of six cancer cell lines, especially in human acute promyelocytic leukaemia HL-60 cells, with an IC50 value of 3.8 µmol. A hypodiploid cells assay and an annexin-V-FITC/PI double staining assay showed a significant increase of apoptosis in a dose-dependent manner on HL-60 cells both 24 and 48 h after MB treatment. MB-induced apoptosis was through the caspase-mediated pathway, by activation of caspase-3. Furthermore, a lactate dehydrogenase (LDH) release test suggested that an MB-cholesterol interaction led to the rearrangement of the lipid bilayer and to subsequent cell membrane impairment. Taken together, these findings demonstrate that MB may exhibit cytotoxic activity against HL-60 cells by inducing apoptosis via caspase-dependent pathways and also membrane permeabilisation.

[The Relationship Between Major Histocompatibility Complex Class I Chain-related Antigens A (MICA)-129 Gene Polymorphism, Soluble MICA Level and Ulcerative Colitis]

Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. Apr, 2011  |  Pubmed ID: 21600151

To investigate the association of the major histocompatibility complex class I chain-related antigens A (MICA)-129 gene polymorphism and soluble MICA (sMICA) levels with ulcerative colitis (UC) in Hubei Han nationality.

Genetics of Inflammatory Bowel Disease in Asia: Systematic Review and Meta-analysis

Inflammatory Bowel Diseases. Sep, 2011  |  Pubmed ID: 21887729

BACKGROUND: Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ between IBD patients in Asia and the West. We aimed to evaluate disease-predisposing genes in Asian IBD patients. METHODS: A systematic review and meta-analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews. RESULTS: In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age- and sex-matched controls. Major nucleotide oligomerization domain (NOD)-2 variants in Western Crohn's disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy-related protein 16-linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84-1.13). Interleukin (IL)-23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16-2.82) and a single nucleotide polymorphism in IL-23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15-0.60). Tumor necrosis factor (TNF) superfamily gene-15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86-3.86), while TNF-308 polymorphisms (OR 1.82; 95% CI 1.15-2.9), cytotoxic T lymphocyte antigen (CTLA)-4 (OR 2.75; 95% CI 1.22-6.22) and MICA allele (OR 2.41; 95% CI 1.89-3.07) were associated with ulcerative colitis in Asians. CONCLUSIONS: Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease-associated mechanisms in this population of rising incidence. (Inflamm Bowel Dis 2011;).

Functional MICA-129 Polymorphism and Serum Levels of Soluble MICA Are Correlated with Ulcerative Colitis in Chinese Patients

Journal of Gastroenterology and Hepatology. Mar, 2011  |  Pubmed ID: 21155878

The aim of the present study was to evaluate the contribution of the dimorphism (MICA-129 val and met) to the genetic susceptibility and functions of ulcerative colitis (UC) in patients in central China.

Epigenetic Regulation of Death-associated Protein Kinase Expression in Primary Gastric Cancers from Chinese Patients

European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP). Oct, 2011  |  Pubmed ID: 21979297

Death-associated protein kinase (DAPK) is a novel serine/threonine kinase involved in apoptosis and tumor suppression. Promoter methylation is an important mechanism by which tumor suppressor gene transcription is repressed in cancer cells. Although reduced expression and aberrant methylation of DAPK has been reported in various human cancers, including gastric cancer (GC), the results remain discrepant. We aimed to investigate DAPK mRNA and protein expression in primary GC tissues from Chinese patients and establish a possible relationship between the promoter methylation status and the decreased expression of DAPK. The mRNA level, protein expression, and promoter methylation of DAPK were examined, in the cancer tissues and the corresponding, adjacent nontumor tissues of the 62 GC cases, by RT-PCR, western blotting and methylation-specific PCR, respectively. DAPK mRNA and protein expression in GC tissues was significantly reduced compared with corresponding nontumor tissues (P<0.0001). The methylation frequency of the DAPK promoter in primary GC tissues is significantly higher than in the corresponding nontumor tissues (54.8 vs. 17.7%, P<0.0001). Furthermore, DAPK mRNA expression in tissues containing aberrant promoter methylation was significantly reduced compared with GC tissues with unmethylated DAPK promoter (P<0.0001). Moreover, a significant correlation was demonstrated between the TNM stage and the degree of DAPK promoter methylation in primary GCs (P=0.04). DAPK protein and mRNA expression was reduced in GC tissues of Chinese patients. Diminished expression of DAPK was associated with promoter methylation.

Tetraspanins Regulate the Protrusive Activities of Cell Membrane

Biochemical and Biophysical Research Communications. Dec, 2011  |  Pubmed ID: 22079629

Tetraspanins have gained increased attention due to their functional versatility. But the universal cellular mechanism that governs such versatility remains unknown. Herein we present the evidence that tetraspanins CD81 and CD82 regulate the formation and/or development of cell membrane protrusions. We analyzed the ultrastructure of the cells in which a tetraspanin is either overexpressed or ablated using transmission electron microscopy. The numbers of microvilli on the cell surface were counted, and the radii of microvillar tips and the lengths of microvilli were measured. We found that tetraspanin CD81 promotes the microvillus formation and/or extension while tetraspanin CD82 inhibits these events. In addition, CD81 enhances the outward bending of the plasma membrane while CD82 inhibits it. We also found that CD81 and CD82 proteins are localized at microvilli using immunofluorescence. CD82 regulates microvillus morphogenesis likely by altering the plasma membrane curvature and/or the cortical actin cytoskeletal organization. We predict that membrane protrusions embody a common morphological phenotype and cellular mechanism for, at least some if not all, tetraspanins. The differential effects of tetraspanins on microvilli likely lead to the functional diversification of tetraspanins and appear to correlate with their functional propensity.

[Correlation of Stromal Cell Derived Factor-1 with Angiogenesis and Cell Apoptosis in Myelodysplastic Syndromes]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Dec, 2011  |  Pubmed ID: 22169299

The study was aimed to investigate the expression of stromal cell derived factor (SDF-1) in bone marrow (BM) and its relation with apoptosis of BM CD34(+) cell and angiogenesis in myelodysplastic syndrome (MDS). 40 patients with MDS were divided into low-risk group and high-risk group according to IPSS score system. BM samples were collected. SDF-1 levels, the apoptosis of CD34(+) cells and microvessel density (MVD) of BM were detected by ELISA, flow cytometry and immunochemistry, respectively. The results showed that the SDF-1 level in MDS patients was significantly higher than that in normal controls(p < 0.05), and SDF-1 level in low-risk group was significantly higher than that in high-risk group. Apoptosis of CD34(+) cells significantly increased in low-risk group compared with other groups (p < 0.05). MVD in BM biopsy significantly increased in high-risk MDS group (p < 0.05), compared with low-risk MDS group which also had higher MVD than the control group (p < 0.05). Positive correlation was found between apoptosis of CD34(+) cells and SDF-1 levels in low-risk group, and SDF-1 level and MVD in high-risk group. It is concluded that the expression of SDF-1, apoptosis of BM CD34(+) cells and MVD were significangtly abnormal in MDS patients, especially in different risk group, suggesting that SDF-1 level is related to cell apoptosis and angiogenesis.

Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains

PLoS Genetics. Dec, 2011  |  Pubmed ID: 22194698

The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with the PALB2 tumor suppressor for activity. Conversely, a BRCA2 fusion peptide deleted for the PALB2 binding domain is dependent on an intact DNA binding domain, providing a role for this conserved domain in vivo; mutagenesis suggests that both single-stranded and double-stranded DNA binding activities in the DNA binding domain are required for its activity. Given that PALB2 itself binds DNA, these results suggest alternative mechanisms to deliver RAD51 to DNA. In addition, the BRCA2 C terminus contains both RAD51-dependent and -independent activities which are essential to HR in some contexts. Finally, binding the small peptide DSS1 is essential for activity when its binding domain is present, but not when it is absent. Our results reveal functional redundancy within the BRCA2 protein and emphasize the plasticity of this large protein built for optimal HR function in mammalian cells. The occurrence of disease-causing mutations throughout BRCA2 suggests sub-optimal HR from a variety of domain modulations.

Molecular Cloning and Characterization of a Phenylalanine Ammonia-lyase Gene (LrPAL) from Lycoris Radiata

Molecular Biology Reports. Mar, 2011  |  Pubmed ID: 20857216

LrPAL is a novel full-length cDNA isolated from Lycoris radiata by degenerate oligonucleotide primer PCR (DOP-PCR), 3'- and 5'-RACE approaches, harbours an open reading frame (ORF) encoding a 708 amino acid product. Sequence alignment showed that the deduced amino acid sequence of LrPAL shared more than 80% identity with other PAL sequences reported in Arabidopsis thaliana and other plants. RT-PCR revealed that LrPAL transcripts were higher in bud flowers and wilting flowers (5 days after blooming) than in blooming flowers. The transcript levels of LrPAL in leaves were significantly induced by methyl jasmonate (MJ) and nitric oxide (NO), and salicylic acid (SA). Similarly, HPLC analysis showed that galantamine (GAL) content was also higher in bud flowers and wilting flowers than in blooming flowers. The GAL content in leaves was significantly induced by MJ and NO, and inhibited by SA. This study enables us to further elucidate the role of LrPAL in the biosynthesis of GAL in Lycoris radiata at a molecular level.

Genetic Polymorphisms of Glutathione S-transferases Are Associated with Ulcerative Colitis in Central China

Cell Biochemistry and Biophysics. Jul, 2011  |  Pubmed ID: 21301992

The present study aimed to investigate the association between genetic polymorphisms of glutathione S-transferases (GSTs) and susceptibility to ulcerative colitis (UC) in central China. The prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms were examined using polymerase chain reaction methods in 270 consecutive UC patients and 623 age- and sex-matched healthy controls. The frequencies of the GSTM1(null) and GSTT1(null) as well as GSTP1 (Val/Val) genotypes were significantly higher in UC patients than in the controls (70.74% vs. 41.74%, P = 0.0001; 64.82% vs. 47.19%, P = 0.0001; and 48.89% vs. 34.35%, P = 0.0004, respectively). When the UC patients were stratified according to clinical features, we found that the frequencies of the GSTT1(null) and GSTP1 (Val/Val) genotypes but not the GSTM1(null) genotype were significantly higher in patients with distal colitis than in extensive colitis (P = 0.0007, P = 0.001, and P = 0.271, respectively). However, these variant GST genotypes were not significantly linked to severity of the disease (P > 0.05). GST variant genotypes are strongly correlated with prevalence and extent but not with severity of UC in the Hubei Han population in central China.

ESIPT-mediated Photocycloadditions of 3-hydroxyquinolinones: Development of a Fluorescence Quenching Assay for Reaction Screening

Organic Letters. Mar, 2011  |  Pubmed ID: 21338078

Irradiation of 1,2-dimethyl-3-hydroxyquinolinone (DMQ) leads to excited state intramolecular proton transfer (ESIPT) generating a 3-oxidoquinolinium species which undergoes [3 + 2] photocycloaddition with dipolarophiles. A parallel, fluorescence quenching assay using a microplate format has been developed to evaluate fluorescence quenching of this species with a range of dipolarophiles.

Removal of Copper Ions from Aqueous Solution by Calcium Alginate Immobilized Kaolin

Journal of Environmental Sciences (China). 2011  |  Pubmed ID: 21520809

Kaolin has been widely used as an adsorbent to remove heavy metal ions from aqueous solutions. However, the lower heavy metal adsorption capacity of kaolin limits its practical application. A novel environmental friendly material, calcium alginate immobilized kaolin (kaolin/CA), was prepared using a sol-gel method. The effects of contact time, pH, adsorbent dose, and temperature on Cu2+ adsorption by kaolin/CA were investigated. The Langmuir isotherm was used to describe the experimental adsorption, the maximum Cu2+ adsorption capacity of the kaolin/CA reached up to 53.63 mg/g. The thermodynamic studies showed that the adsorption reaction was a spontaneous and endothermic process.

Eugene--a Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems

PloS One. 2011  |  Pubmed ID: 21559524

Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts.

The Effect of Bioequivalent Radiation Dose on Survival of Patients with Limited-stage Small-cell Lung Cancer

Radiation Oncology (London, England). 2011  |  Pubmed ID: 21592406

To investigate the biological radiation dose-response for patients of limited-stage small-cell lung cancer (LS-SCLC) treated with high radiation dose.

Effect of Bone Sialoprotein on Proliferation and Osteodifferentiation of Human Bone Marrow-derived Mesenchymal Stem Cells In Vitro

Biologicals : Journal of the International Association of Biological Standardization. Jul, 2011  |  Pubmed ID: 21600786

We performed this study to investigate the effects of recombinant human bone sialoprotein (BSP) on the proliferation and osteodifferentiation of human BMSCs(hBMSCs). The hBMSC cultures were divided into 4 groups: control group, 10(-10) M BSP group (BSP group), osteogenic medium group (10 nM dexamethasone, 10 mM β-glycerophosphate, and 50 mg/L ascorbic acid, OM group) and BSP + OM group (OM plus10(-10) M BSP). Compared with the control group, cell growth of the other three groups slowed down, while fluorescence at the G(0)/G(1) phase increased. After 28 days, in the OM group and the BSP + OM group, the proportion of STRO-1-positive cells decreased by 22.7% and 38.4% and ALP activity increased by 50% and 71.43%, respectively. CD271 mRNA expression decreased while Cbfa1, osteocalcin and osterix mRNA levels increased in the OM and BSP + OM groups, and the mRNA level change was greater in the BSP + OM group. After 28 days, the number of nodules in the BSP + OM group was 112.5% more than that in the OM group, but nodules did not formed in the control or BSP group. We conclude that BSP is capable of inhibiting hBMSCs proliferation and enhancing their osteogenic differentiation and mineralization in the presence of OM.

Developer's and User's Guide to Clotho V2.0 A Software Platform for the Creation of Synthetic Biological Systems

Methods in Enzymology. 2011  |  Pubmed ID: 21601675

To design the complex systems that synthetic biologists propose to create, software tools must be developed. Critical to success is the enablement of collaboration across our community such that individual tools that perform specific tasks combine with other tools to provide multiplicative benefits. This will require standardization of the form of the data that exists within the field (Parts, Strains, measurements, etc.), a software environment that enables communication between tools, and a sharing mechanism for distributing the tools. Additionally, this data model must describe the data in a sufficiently rigorous and validated form such that meaningful layers of abstraction can be built upon the base. Herein, we describe a software platform called "Clotho" which provides such a data model, and the plugin and sharing mechanisms needed for a rich tool environment. This document provides a tutorial for users of Clotho and information for software developers who wish to contribute new tools (known as "Apps") to it.

[Inhibitory Effect of Bone Sialoprotein Silencing on the Adhesion Ability of Breast Cancer Cells to Bone Matrix]

Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology. Feb, 2011  |  Pubmed ID: 21650048

We performed this research mainly to explore the effect of bone sialoprotein (BSP) silence by siRNA on the adhesion ability to bone matrix of bone-seeking breast cancer cells (MDA-MB-231BO). Also we aimed to provide experimental data for prevention and treatment of breast cancer bone metastasis by targeting BSP. We explored the effects of BSP gene silence on characteristics of bone-seeking breast cancer cells: proliferation by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay, bone adhesion ability by a mouse bone adhesion model in vitro, morphology of the cells by SEM, and secretion of transforming growth factor-beta1 (TGF-beta1) and receptor activator of nuclear factor-kappa B ligand (RANKL) by ELISA kits. We performed intra-cardiac injection in nude mice to explore bone metastatic ability of different cell lines. The results showed that knockdown of BSP significantly inhibited the proliferation of MDA-MB-231BO cells and their adhesion to bone matrix. We also observed bone destruction caused by bone resorption around some adhering cells. The appearances of the cells changed in BSP gene silenced group, and the secretion of TGF-beta1 and RANKL decreased. The results showed BSP gene silence can partial inhibition bone metastasis of breast cancer cells in nude mice by X-ray assay and hematoxylin-eosin staining. Based on our research, siRNA-mediated BSP silencing can inhibit proliferation and adhesion to bone matrix of bone-seeking breast cancer cells and change their surface structure, thus inhibits their bone metastatic ability.

Amyloid Histology Stain for Rapid Bacterial Endospore Imaging

Journal of Clinical Microbiology. Aug, 2011  |  Pubmed ID: 21653779

Bacterial endospores are some of the most resilient forms of life known to us, with their persistent survival capability resulting from a complex and effective structural organization. The outer membrane of endospores is surrounded by the densely packed endospore coat and exosporium, containing amyloid or amyloid-like proteins. In fact, it is the impenetrable composition of the endospore coat and the exosporium that makes staining methodologies for endospore detection complex and challenging. Therefore, a plausible strategy for facile and expedient staining would be to target components of the protective surface layers of the endospores. Instead of targeting endogenous markers encapsulated in the spores, here we demonstrated staining of these dormant life entities that targets the amyloid domains, i.e., the very surface components that make the coats of these species impenetrable. Using an amyloid staining dye, thioflavin T (ThT), we examined this strategy. A short incubation of bacillus endospore suspensions with ThT, under ambient conditions, resulted in (i) an enhancement of the fluorescence of ThT and (ii) the accumulation of ThT in the endospores, affording fluorescence images with excellent contrast ratios. Fluorescence images revealed that ThT tends to accumulate in the surface regions of the endospores. The observed fluorescence enhancement and dye accumulation, coupled with the sensitivity of emission techniques, provide an effective and rapid means of staining endospores without the inconvenience of pre- or posttreatment of samples.

A Function for Cyclin D1 in DNA Repair Uncovered by Protein Interactome Analyses in Human Cancers

Nature. Jun, 2011  |  Pubmed ID: 21654808

Cyclin D1 is a component of the core cell cycle machinery. Abnormally high levels of cyclin D1 are detected in many human cancer types. To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process. We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation. These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition.

MyMolDB: a Micromolecular Database Solution with Open Source and Free Components

Journal of Computational Chemistry. Oct, 2011  |  Pubmed ID: 21728180

To manage chemical structures in small laboratories is one of the important daily tasks. Few solutions are available on the internet, and most of them are closed source applications. The open-source applications typically have limited capability and basic cheminformatics functionalities. In this article, we describe an open-source solution to manage chemicals in research groups based on open source and free components. It has a user-friendly interface with the functions of chemical handling and intensive searching.

Synthesis of Isoreticular Zinc(II)-phosphonocarboxylate Frameworks and Their Application in the Friedel-Crafts Benzylation Reaction

Chemistry (Weinheim an Der Bergstrasse, Germany). Sep, 2011  |  Pubmed ID: 21818796

Three isoreticular zinc(II)-phosphonocarboxylate frameworks, namely {[Zn(3)(pbdc)(2)]·2H(3)O}(n) (ZnPC-2), {[Zn(3)(pbdc)(2)]·Hpd·H(3)O·4H(2)O}(n) (Hpd@ZnPC-2) and {[Co(1.5)Zn(1.5)(pbdc)(2)]·2H(3)O}(n) (CoZnPC-2) (H(4)pbdc=5-phosphonobenzene-1,3-dicarboxylic acid, pd=pyrrolidine), were solvothermally synthesized. ZnPC-2 has a 3D structure based on trinuclear Zn(II) clusters (Zn(3)-SBU) showing 3D interconnected channels. Hpd@ZnPC-2 contains an isoreticular framework of ZnPC-2 with small channels blocked by Hpd molecules. In CoZnPC-2, Zn(II) ions in ZnPC-2 are partially substituted by Co(II) ions. The Friedel-Crafts benzylation reactions were carried out over these isoreticular porous materials. The catalytic results reveal that ZnPC-2 is an excellent heterogeneous Lewis acid catalyst with a high selectivity (>90%) towards less bulky para-oriented products. The catalytic reaction has been proved to occur inside the pore of ZnPC-2, and the immobilized Zn(3)-SBUs are the active sites.

Discrimination of the Seeds of Notopterygium Incisum and Notopterygium Franchetii by Validated HPLC-DAD-ESI-MS Method and Principal Component Analysis

Journal of Pharmaceutical and Biomedical Analysis. Dec, 2011  |  Pubmed ID: 21856104

A validated HPLC-DAD-ESI-MS method has been developed to simultaneously quantify 12 bioactive compounds in the seeds of Notopterygium incisum Ting ex H.T. Chang and Notopterygium franchetii H. de Boiss whose rhizomes and roots are widely used as traditional Chinese medicine. This method was validated to be sensitive, precise and accurate and was applied to evaluate the difference in the chemical profiles and contents of these analytes in 37 batches of N. incisum and 31 batches of N. franchetii samples collected from different locations. Principal component analysis showed that the two species were separated into two groups obviously. This study established a validated method for identification of the authenticity of the seeds of N. incisum and N. franchetii and supplied effective guidance for artificial cultivation.

Hyperhomocysteinemia and Related Genetic Polymorphisms Correlate with Ulcerative Colitis in Southeast China

Cell Biochemistry and Biophysics. Jan, 2012  |  Pubmed ID: 21947961

Increased levels of homocysteine are found systemically and in intestinal mucosa of patients with inflammatory bowel disease, and, specifically, in ulcerative colitis (UC). However, there are controversial reports regarding the factors contributing to increased levels of homocysteine in UC. Furthermore, little information is available regarding the relationship between hyperhomocysteinemia (HHcy), vitamin status, and genetic polymorphisms of homocysteine-related enzymes in these patients. This study examined four functional polymorphisms linked to homocysteine metabolism (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G), and evaluated plasma levels of homocysteine, folate, and vitamin B(12) in 310 consecutive patients with UC and 936 age- and sex-matched healthy controls from southeast China. The variant allele and genotypic frequencies in MTHFR A1298C, MTR A2756G and MTRR A66G genes were significantly higher in patients with UC compared to healthy controls. Further, HHcy and low levels of folate and vitamin B(12) were more frequent in patients with UC. The MTR 2756G allele, extent of the disease, and gender were the independent determinants of HHcy in these patients. These findings suggest that genetic and nutritional factors have a synergetic effect on HHcy in patients with UC. In conclusion, our data highlight a prevention strategy for moderation of HHcy and supplementation with folate and vitamine B(12) in patients with UC from Southeast China.

Akt Inhibitors MK-2206 and Nelfinavir Overcome MTOR Inhibitor Resistance in DLBCL

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Feb, 2012  |  Pubmed ID: 22338016

PURPOSE: The mTOR (mammalian Target of Rapamycin) pathway is constitutively activated in Diffuse Large B-Cell Lymphoma (DLBCL). mTOR inhibitors (mTORi) have activity in DLBCL, although response rates remain low. We evaluated DLBCL cell lines with differential resistance to the mTORi Rapamycin, in order to (A) identify gene-expression profile(s) (GEP) associated with resistance to Rapamycin, (B) understand mechanisms of Rapamycin resistance, and (C) identify compounds that synergize with mTORi. EXPERIMENTAL DESIGN: We sought to identify a GEP of mTORi resistance by stratification of eight DLBCL cell lines with respect to response to Rapamycin. Then, using pathway analysis and connectivity mapping, we sought targets likely accounting for this resistance, and compounds likely to overcome it. We evaluated two compounds thus identified for their potential to synergize with Rapamycin in DLBCL, and confirmed mechanisms of activity with standard immunoassays.RESULTS: We identified a GEP capable of distinguishing Rapamycin resistant from Rapamycin sensitive DLBCL cell lines. Pathway analysis identified Akt as central to the differentially expressed gene network. Connectivity mapping identified compounds targeting Akt as having a high likelihood of reversing the GEP associated with mTORi resistance. Nelfinavir and MK-2206, chosen for their Akt-inhibitory properties, synergistically inhibited cell viability in combination with Rapamycin in DLBCL cell lines, and potently inhibited phosphorylation of Akt and targets of activated mTOR. CONCLUSIONS: GEP identifies DLBCL subsets resistant to mTORi therapy. Combined targeting of mTOR and Akt suppresses key components of the Akt/mTOR pathway and results in synergistic cytotoxicity. These findings are readily adaptable to clinical trials.

Is Involved-field Radiotherapy Based on CT Safe for Patients with Limited-stage Small-cell Lung Cancer?

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. Feb, 2012  |  Pubmed ID: 22056536

To examine the pattern of failures in patients with limited-stage small-cell lung cancer (LS-SCLC) treated with involved-field radiotherapy (IFRT) and chemotherapy, with the aim of investigating the safety of IFRT.

Erratum To: Hyperhomocysteinemia and Related Genetic Polymorphisms Correlate with Ulcerative Colitis in Chinese Han Population in Central China

Cell Biochemistry and Biophysics. Jan, 2012  |  Pubmed ID: 22258714

Hypermethylation of SHP-1 Promoter in Patient with High-risk Myelodysplastic Syndrome and It Predicts Poor Prognosis

Medical Oncology (Northwood, London, England). Jan, 2012  |  Pubmed ID: 22258937

To study the role of SHP-1 methylation in the pathogenesis of myelodysplastic syndromes (MDS), we detect the methylation status of SHP-1 promoter and STAT3 phosphorylation of MDS patients by the methylation-specific PCR and Western blotting, respectively. It is found that the methylation rate of SHP-1 promoter of high-risk MDS patients (69.2%) was higher than that of the low-risk MDS patients (21.4%) (P = 0.001). The expression rate of STAT3 phosphorylated protein of high-risk group was higher (66.7%), when compared with that of the low-risk group (18.2%) (P = 0.0001). Correlation analysis showed that the methylation status of SHP-1 promoter is positive correlated with the expression of phosphorylated STAT3 in MDS patient (P < 0.001, r = 0.55). Interestingly, in high-risk group, the Kaplan-Meier analysis showed that the 3-year overall survival rate of high-risk MDS patients with SHP-1 methylation was lower than that of patient without SHP-1 methylation (25% vs. 61%) (P = 0.033). In summary, it is indicated that the SHP-1 methylation plays important role in the pathogenesis of MDS via activating the JAK/STAT pathway probably and the methylation of SHP-1 promoter is a useful prognostic factor for high-risk MDS patient, with the characteristic of higher methylation lower survival rate.

PALB2 Interacts with KEAP1 to Promote NRF2 Nuclear Accumulation and Function

Molecular and Cellular Biology. Feb, 2012  |  Pubmed ID: 22331464

PALB2/FANCN is mutated in breast and pancreatic cancers and Fanconi anemia (FA). It controls the intra-nuclear localization, stability and DNA repair function of BRCA2 and links BRCA1 and BRCA2 in DNA homologous recombination repair and breast cancer suppression. Here we show that PALB2 directly interacts with KEAP1, an oxidative stress sensor that binds and represses the master anti-oxidant transcription factor NRF2. PALB2 shares with NRF2 a highly conserved "ETGE"-type KEAP1-binding motif and can effectively compete with NRF2 for KEAP1 binding. PALB2 promotes NRF2 accumulation and function in the nucleus and lowers cellular reactive oxygen species (ROS) level. In addition, PALB2 also regulates the rate of NRF2 export from nucleus following induction. Our findings identify PALB2 as a regulator of cellular redox homeostasis and provide a new link between oxidative stress and the development of cancer and FA.