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Biomedical subjects

X Sun

Publications and source records attributed to X Sun.

At least 55 records · Page 3Linked to original sources
PubMed2003

Genetic and physical mapping of a new gene for bacterial blight resistance in rice.

The inheritance of resistance for bacterial blight, caused by Xanthomonas oryzae pv. oryzae ( Xoo), was studied in Minghui 63, an elite restorer line for a number of widely used rice hybrids in China. A new dominant gene against a Chinese Xoo strain JL691 in both the seedling and adult stages was identified in Minghui 63 and designated as Xa26( t). Using a total of 477 highly susceptible individuals from an F(2) population, the Xa26( t) locus was mapped to a region of about 1.68 cM. This locus co-segregated with marker R1506 and was 0.21 cM from marker RM224 on one side and 1.47 cM from marker Y6855RA on the other side, in rice chromosome 11. A contig map, composed of five non-redundant bacterial artificial chromosome (BAC) clones and spanning approximately 500 kb in length, was constructed. Analysis of recombination events in the Xa26( t) region with the highly susceptible F(2) individuals anchored the gene locus to a region covered by three overlapped BAC clones. Assay of the lines showing a double crossover in marker loci flanking Xa26( t), in a population of recombinant inbred lines carrying Xa26( t), further delineated the gene to a 20-kb fragment. The Xa26( t) locus is tightly linked to another bacterial blight resistance gene locus, Xa4.

Chromosomes, Artificial, Bacterial↗
PubMed2003

20E-regulated USP expression and phosphorylation in Drosophila melanogaster.

The developmental profiles of ultraspiracle protein (USP) in the tissues of Drosophila melanogaster were investigated using a USP specific monoclonal antibody (mAb) as a probe. Western blot analysis revealed four USP mAb reactive bands (p46, p48, p54 and p56), each with tissue- and stage-specific expression patterns. The p54 and p56 were expressed in nearly all larval and prepupal tissues tested with fluctuations in abundance. However, the p46 and p48 were detected exclusively in the midgut of prepupae and shown to be the proteolytic products of p54 and p56. A lambda protein phosphatase assay demonstrated that the p56 is the phosphorylated form of p54. The expression and phosphorylation of the p54 USP is regulated by 20E. Protein kinase consensus recognition sequence analysis revealed 10 putative phosphorylation sites in Drosophila USP, with seven sites for protein kinase C (PKC) and three sites for casein kinase II (CKII). The fact that seven out of 10 putative phosphorylation sites reside in the ligand- and DNA-binding domains suggests that phosphorylation may play important role in regulating USP function. Identification of the in vivo USP phosphorylation sites and signal transduction pathways that regulate the specific USP phosphorylation is currently underway.

Animals↗
PubMed2003

Effects of ecdysone agonists on the expression of EcR, USP and other specific proteins in the ovaries of the codling moth (Cydia pomonella L.).

Tebufenozide and methoxyfenozide have been previously shown to significantly reduce fecundity and cause vitellogenin accumulation in hemolymph of the codling moth Cydia pomonella L. In the present study, the effects of these ecdysone agonists, tebufenozide and methoxyfenozide, on the expression of ecdysone receptor (EcR), ultraspiracle protein (USP) and other proteins in the ovaries of C. pomonella L., were investigated at both the translational and/or transcriptional levels with an aim to elucidate the mechanisms by which the fecundity was reduced. Western and Northern blot analyses revealed that the expression of a 65 kDa (p65) EcR, and 60 and 64 kDa (p60 and p64) USP proteins were enhanced by tebufenozide and methoxyfenozide at both transcriptional and translational levels. Northern blot analysis indicated that the p65 EcR protein is encoded by EcRB1 transcript and that the p60 and p64 USP bands were the products of USP-1 transcript. Immunoprecipitation assays demonstrated that both the p60 and p64 USP coprecipitated with the p65 EcR and that p64 was a dominant USP to form complex with EcR. In addition, several other specific proteins were also identified and their expressions affected by the agonists. The data suggest that the ecdysone agonists regulate, via the EcR/USP complex, the expression of these specific proteins that might eventually lead to the inhibition of fecundity in the codling moth.

Animals↗
PubMed2003

Mouse B7-H3 induces antitumor immunity.

Members of the B7 family costimulate the proliferation of lymphocytes during the initiation and maintenance of antigen-specific humoral and cell-mediated immune responses. While B7-1 and -2 are restricted to lymphoid tissues, and activate naïve T cells, recently identified members including B7-H2 and -H3 are widely expressed on nonlymphoid tissues, and regulate effector lymphocytes in the periphery. B7-H3 has properties that suggested it may display antitumor activity, including the ability to stimulate Th1 and cytotoxic T-cell responses. Here, we test this notion by determining whether intratumoral injection of an expression plasmid encoding a newly described mouse homologue of B7-H3 is able to eradicate EL-4 lymphomas. Intratumoral injection of a mouse B7-H3 pcDNA3 expression plasmid led to complete regression of 50% tumors, or otherwise significantly slowed tumor growth. Mice whose tumors completely regressed resisted a challenge with parental tumor cells, indicating systemic immunity had been generated. B7-H3-mediated antitumor immunity was mediated by CD8(+) T and NK cells, with no apparent contribution from CD4(+) T cells. In summary, the results indicate that B7-H3 interactions may play a role in regulating cell-mediated immune responses against cancer, and that B7-H3 is a potential therapeutic tool.

Amino Acid Sequence↗
PubMed2003

Regression of solid tumors by engineered overexpression of von Hippel-Lindau tumor suppressor protein and antisense hypoxia-inducible factor-1alpha.

The von Hippel-Lindau tumor suppressor protein (pVHL) suppresses tumor formation by binding the alpha subunits of hypoxia-inducible factors (HIFs) responsible for stimulating tumor angiogenesis and glycolysis, targeting them for ubiquitination and proteasomal destruction. Loss of pVHL leads to the development of sporadic renal cell carcinomas (RCCs). In the present study, we sought to determine whether engineered overexpression of pVHL in tumors other than RCC can inhibit tumor growth, either as a monotherapy, or in combination with antisense HIF-1alpha therapy. Intratumoral injection of subcutaneous EL-4 thymic lymphomas with an expression plasmid encoding pVHL resulted in the downregulation of HIF-1alpha and vascular endothelial growth factor (VEGF). There was a concomitant reduction in tumor angiogenesis and increased tumor cell apoptosis due in part to downregulation of Bcl-2 expression. VHL therapy resulted in the complete regression of small (0.1 cm diameter) tumors whereas, in contrast, large (0.4 cm diameter) EL-4 tumors were only slowed in their growth. Nevertheless, large tumors completely regressed in response to intratumoral injection of a combination of antisense HIF-1alpha and VHL plasmids. Combination therapy resulted in increased losses of HIF-1alpha, VEGF, and tumor blood vessels, and increased tumor cell apoptosis. These novel results suggest that synergistic therapies that simultaneously block the expression or function of HIF-1alpha, and enhance the expression or function of VHL may be beneficial in the treatment of cancer.

Angiogenesis Inhibitors↗
PubMed2003

Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment.

We aimed to assess the clinical performance of a newly developed chemiluminescence enzyme immunoassay (CLEIA) for the detection of hepatitis B virus (HBV) core-related antigen (HBcrAg) in patients with chronic HBV infection. A total of 82 patients with chronic HBV infection and 167 HBV-negative controls were studied. HBcrAg was measured by CLEIA with monoclonal antibodies to hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg), and HBV DNA was measured by transcription-mediated amplification assay (TMA) and in-house real-time detection polymerase chain reaction (RTD-PCR). The HBcrAg assay detected viremia in 189 of 216 samples (88%) collected from 72 patients whilst the TMA assay detected viremia in 178 of the 216 samples (82%) (P = 0.019). The HBcrAg concentration correlated linearly with the HBV DNA concentration (P < 0.001) over a range which varied 100 000-fold. The accuracy in the measurement of the patients' HBV load obtained using the HBcrAg assay was not affected by the absence of hepatitis B e antigen from the serum or the presence of precore mutations in the HBV genome. In patients without anti-viral drugs, changes in their serum HBcrAg concentration over time corresponded to their HBV DNA concentration. In six additional patients who were later treated with lamivudine, HBV DNA concentration declined more rapidly than their HBcrAg concentration. Three months after treatment commenced, the ratio of HBcrAg: HBV DNA had increased in all six patients (P = 0.031). The HBcrAg assay is a sensitive and useful test for the assessment of a patient's HBV load. When monitoring the anti-viral effect of lamivudine, HBcrAg provides a viral marker which is independent of HBV DNA.

Biomarkers↗
PubMed2003

Neuroprotective effects of tanshinones in transient focal cerebral ischemia in mice.

Tanshinones are the major lipid soluble pharmacological constituents of Danshen, the dried roots of Salvia miltiorrhiza Bunge (Labiatae), a well known traditional Chinese medicine used for the treatment of cerebrovascular diseases including stroke. Potential neuroprotective effects of tanshinones IIA (TsIIA) and IIB (TsIIB) were examined in adult mice subjected to transient focal cerebral ischemia caused by middle cerebral artery occlusion (MCAo). Our results revealed that TsIIA (16 mg/kg) readily penetrated the blood brain barrier reaching a peak concentration of 0.41 nmol/g brain wet weight 60 minutes after intraperitoneal injection and decreased slowly over several hours. Twenty-four hours after middle cerebral artery occlusion, brain infarct volume was reduced by 30% and 37% following treatment with TsIIA and TsIIB, respectively. The reduction in brain infarct volume was accompanied by a significant decrease in the observed neurological deficit. Tanshinones or other structurally related compounds may have potential for further development as neuroprotective drugs.

Abietanes↗
PubMed2003

Characterization of two novel KRAB-domain-containing zinc finger genes, ZNF460 and ZNF461, on human chromosome 19q13.1-->q13.4.

This study reports the cloning and characterization of two novel human zinc finger protein cDNAs (ZNF460 and ZNF461) from a fetal brain cDNA library. The ZNF460 cDNA is 3,135 bp in length encoding a 562-amino-acid polypeptide and the ZNF461 cDNA is 2,548 bp encoding a 563-amino-acid protein. Both of the proteins contain a KRAB A+B box and eleven C2H2 type zinc finger motifs. ZNF461 shows high similarity with the rat GIOT-1 gene (GIOT1). The ZNF460 gene mapped to 19q13.4 with 3 exons, and ZNF461 mapped to 19q13.1 with 6 exons. Both of the two genes are ubiquitously expressed in normal human tissues and the abundance of the ZNF460 mRNA is relatively low.

Amino Acid Sequence↗
PubMed2002

Identification of a 47-kb DNA fragment containing Xa4, a locus for bacterial blight resistance in rice.

Bacterial blight caused by Xanthomonas oryzae pv oryzae is a devastating disease in rice worldwide. The resistance gene Xa4 has been widely used in breeding programs and played an important role in protecting rice from this disease. Using 642 highly susceptible individuals and a random sample of 255 individuals from an F(2) population developed from a cross between IRBB4 and IR24, the Xa4 gene was genetically mapped to a region less than 1 cM. A contig map was constructed for the Xa4 region consisting of six non-redundant bacterial artificial chromosome (BAC) clones and spanning approximately 500 kb in length. Analysis of recombination events in the Xa4 region located the gene locus to one BAC, 3H8. Assay of the recombinants using the subclones of 3H8 in combination with sequence analysis further narrowed the Xa4 locus down to a 47-kb fragment.

Chromosome Mapping↗
PubMed2002

RF absorption and ion heating in helicon sources.

Experimental data are presented that are consistent with the hypothesis that anomalous rf absorption in helicon sources is due to electron scattering arising from parametrically driven ion-acoustic waves downstream from the antenna. Also presented are ion temperature measurements demonstrating anisotropic heating (T( perpendicular)>T(parallel)) at the edge of the discharge. The most likely explanation is ion-Landau damping of electrostatic slow waves at a local lower-hybrid-frequency resonance.

Journal Article↗
PubMed2002

Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100.

To examine the regulation of amyloid secretion in more detail, Abeta sandwich ELISAs with high sensitivity and specificity were developed. Using this technique, we measured Abeta secreted from COS7 cells transiently transfected with APP C100 in the presence of LiCl, a potent glycogen synthase kinase (GSK)-3beta inhibitor. We found that both Abetax-40 and Abetax-42 secretion were reduced by LiCl treatment in a dose-dependent manner. Diminished amyloid secretion was associated with GSK-3beta activity. These results suggest that GSK-3beta might function as a possible mediator for regulating both amyloid deposition and tau pathology in Alzheimer's disease (AD), and that lithium should be re-evaluated as a candidate reagent for preventing AD pathology.

Alzheimer Disease↗
PubMed2002

Melatonin blocks rat hippocampal neuronal apoptosis induced by amyloid beta-peptide 25-35.

To investigate whether melatonin protects neurons from apoptosis. we used amyloid beta-peptide 25-35 (Abeta(25-35)) to induce apoptosis in cultured hippocampal neurons, and monitored the apoptotic activity of the neurons with or without melatonin treatment. Present study shows that melatonin at concentrations of 1 x 10(-6) and 1 x 10(-5) mol/L prevents neuronal morphological changes induced by apoptosis, as characterized by the shrunken and rounded morphology caused by condensed chromatin and fragmented DNA. Melatonin further exhibited the ability to inhibit apoptotic internucleosomal DNA degradation. Moreover, flow cytometric analysis of cell cycle demonstrated that melatonin abolished the Abeta(25-35)-induced apoptotic peak. Our results suggest that melatonin may play an important role to protect neurons from Abeta(25-35)-induced apoptosis.

Amyloid beta-Peptides↗
PubMed2002

Effect of mifepristone and levonorgestrel on expression of steroid receptors in the human Fallopian tube.

It is likely that mifepristone or levonorgestrel in the future will find extended use for contraceptive purposes. It is therefore essential to characterize the modes of action of these compounds. To assess the effect on the human Fallopian tube, 24 women with regular menstrual cycles and proven fertility, admitted to the hospital for voluntary sterilization by laparoscopic technique, were randomly allocated to a control or one of two treatment groups. Treatments were given with either a single dose of 200 mg mifepristone or 0.75 mg levonorgestrel in two doses 12 h apart, on day LH+2. Surgery was performed on day LH+4 to LH+6. Steroid receptor expression was analysed by immunohistochemistry, Western blot and RT-PCR. In the controls, there was a higher concentration of progesterone receptors in the stromal cells in the isthmic region than in those in the ampullar region. Treatment with mifepristone increased the progesterone receptor concentration in epithelial and stromal cells and increased the estrogen receptor concentration in epithelial cells. No effect on steroid receptor concentration was found following levonorgestrel. The contraceptive effect of post-ovulatory mifepristone has previously been considered to be dependent on an effect on the endometrium. However an effect on the Fallopian tube could contribute to alter the peri-implantation milieu influencing fertilization and embryo development.

Adult↗
PubMed2002

A matrix-assisted laser desorption/ionization time-of-flight based method for screening the 1691G --> A mutation in the factor V gene.

A point mutation, 1691 G --> A in the coagulation factor V gene results in an Arg506 --> Gln amino acid substitution in the factor V molecule. This mutation, defined as factor VLEIDEN, results in activated protein C (APC) resistance and is the most common genetic risk factor for familial thrombophilia. A new mini-sequencing method using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was developed for the screening of the 1691G --> A substitution in factor V. In this method, a fragment of genomic DNA containing the 1691st base is first amplified, followed by mini-sequencing in the presence of dGTP and ddATP, ddCTP, and ddTTP. In this manner, the primer is extended by one base from one allele and two bases from the other allele. The extended products are analyzed using MALDI-TOF mass spectrometry. The base at position 1691 is identified based on the number of nucleotides added. We have used this method to genotype 16 APC-resistant patients previously identified by conventional methods and 11 normal control samples. The genotypes of all samples were correctly identified. This method is accurate, fast, and potentially allows for simultaneous multiplex genotyping of a number of mutation sites associated with thrombophilia and clot formation.

Activated Protein C Resistance↗
PubMed2002

Photodynamic effects of mTHPC on human colon adenocarcinoma cells: photocytotoxicity, subcellular localization and apoptosis.

The photodynamic properties of meta-tetra(hydroxyphenyl)chlorin (mTHPC), a promising second-generation photosensitizer, were investigated using a human colon adenocarcinoma cell line (Colo 201 cells). The study on photocytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay showed that mTHPC was an effective photosensitizer on Colo 201 cells. The photocytotoxicity of mTHPC showed both drug and light dose-dependent characteristics. To reach LD50, namely, the dose at which 50% of the cells were killed, only 0.45+/-0.15 microg/mL of mTHPC and 3 J/cm2 of light dose were required. The presence of 10% fetal calf serum in culture medium significantly decreased the incorporation of mTHPC into cells and resulted in the reduction of photodynamic efficacy. Using confocal laser scanning microscopy, mTHPC was first shown to localize in lysosomes rather than in mitochondria. Furthermore, nuclear stainings demonstrated that photodynamic therapy with mTHPC induced apoptosis in Colo 201 cells.

Adenocarcinoma↗
PubMed2002

Photodynamic therapy with pyropheophorbide-a methyl ester in human lung carcinoma cancer cell: efficacy, localization and apoptosis.

Pyropheophorbide-a methyl ester (MPPa) is a semisynthetic photosensitizer derived from chlorophyll a. The absorption peak of MPPa in organic solvent and in cells was at 667 and 674 nm, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay showed that MPPa had no dark cytotoxicity. In vitro photodynamic activity was extensively evaluated using a human lung carcinoma cancer cell line (NCI-h446). MPPa exhibited no genotoxicity, as assayed by single-cell gel electrophoresis. Using confocal laser scanning microscopy and organelle-specific fluorescent probes, MPPa was found to localize in the intracellular membrane system, namely the endoplasmic reticulum, Golgi apparatus, lysosomes and mitochondria, in the NCI-h446 cells. Furthermore, nuclear staining and DNA gel electrophoresis revealed that DNA condensation and fragmentation occurred post-photodynamic therapy, indicating the cell death was in the apoptotic mode.

Apoptosis↗
PubMed2001

Synthesis and evaluation of novel pseudomycin side-chain analogues. Part 3.

To increase the therapeutic utility of C-18 side-chain bearing pseudomycin analogue 2, we prepared additional analogues and prodrugs of 2 containing further modifications at various positions within its core structure. Each of the newly synthesized derivatives (10-15) exhibited reduced tail vein toxicity relative to the parent compound. Some of the new pseudomycin derivatives (e.g., 14) also showed improved in vivo antifungal activity relative to its corresponding parent compound.

Animals↗