PubMed Health⌕ Search

Biomedical subjects

X M Liu

Publications and source records attributed to X M Liu.

At least 19 recordsLinked to original sources

Dual action on promoter demethylation and chromatin by an isothiocyanate restored GSTP1 silenced in prostate cancer.

Prostate carcinoma is characterized by the silencing of pi-class glutathione S-transferase gene (GSTP1), which encodes a detoxifying enzyme. The silencing of GSTP1, due to aberrant methylation at the CpG island in the promoter/5'-UTR, occurs in the vast majority of prostate tumors and precancerous lesions. It is a pathologic marker and probably an underlying cause of oxidative damage and inflammation at tumor initiation. Inhibition of the aberrant promoter methylation could therefore be an effective mean to prevent carcinogenesis. Several isothiocyanates, including phenethyl isothiocyanate (PEITC), found naturally in cruciferous vegetables, induced growth arrest and apoptosis in prostate cancer cells in culture and xenografts. The effects of PEITC to reactivate GSTP1 were investigated. Exposure of prostate cancer LNCaP cells to PEITC inhibited the activity and level of histone deacetylases (HDACs), and induced selective histone acetylation and methylation for chromatin unfolding. Concurrently PEITC demethylated the promoter and restored the unmethylated GSTP1 in both androgen-dependent and -independent LNCaP cancer cells to the level found in normal prostatic cells, as quantified by methylation-specific PCR and pyrosequencing. The dual action of PEITC on both the DNA and chromatin was more effective than 5'-Aza-2'-deoxycytidine, sodium butyrate, or trichostatin A (TSA), and may de-repress the methyl-binding domain (MBD) on gene transcription. The PEITC-mediated cross-talk between the DNA and chromatin in demethylating and reactivating GSTP1 genes, which is critically inactivated in prostate carcinogenesis, underlines a primary mechanism of cancer chemoprevention. Consequently, new approaches could be developed, with isothiocyanates to prevent and inhibit malignancies.

Acetylation↗

H22, a major resistance gene to the Hessian fly (Mayetiola destructor), is mapped to the distal region of wheat chromosome 1DS.

H22 is a major resistance gene conferring high-level of antibiosis to Hessian fly [Mayetiola destructor (Say)] larvae. It was previously assigned to wheat chromosome 1D through monosomic analysis (Raupp et al. in J Hered 84:142-145, 1993). The objective of this study was to identify molecular markers that can be used for marker-assisted selection for wheat breeding, and to further map this gene toward map-based cloning. Forty-five simple sequence repeat (SSR) and sequence-tagged site (STS) markers specific to chromosome 1D were evaluated for linkage to H22 using a segregating population consisting of 192 F(2:3) families, which were derived from the cross Tugela-Dn1 x KS85WGRC01(H22). The STS Xhor2kv and SSR Xgdm33 are two flanking markers that are tightly linked to H22 at genetic distances of 0.3 and 1.0 cM, respectively. Five other SSR markers including Xgpw7082, Xwmc147, Xcfd15, Xwmc432 and Xwmc336 were also linked to H22 at the distance from 0.8 to 20.8 cM. Analysis of Chinese Spring (CS) deletion lines revealed that all the H22-linked markers are located distal to the breakpoint of del 1DS-5, indicating that the H22 gene is located at the distal 30% region on the short arm of wheat chromosome 1D. Genomic comparison suggested that the H22 gene is located in the same or similar chromosomal region as the leaf rust resistance genes Lr21 and Lr40 on 1DS, and orthologous to the H9 gene cluster of 1AS.

Animals↗

Repression of androgen receptor in prostate cancer cells by phenethyl isothiocyanate.

BACKGROUND: Prostate cancer usually progresses to androgen refractory after an initial anti-androgen treatment. The androgen receptor (AR) is a pivotal factor for the androgen-mediated growth and maintenance of the prostate. Abnormality of the AR, such as overexpression has been postulated to be related to the hormone independent growth of the cancer. Although we previously demonstrated that the AR expression could be modulated by isothiocyanates, which are natural constituents of cruciferous vegetables, the mechanism, however, remained to be clarified. We have since investigated the mechanism of phenethyl isothiocyanate (PEITC) in AR regulation. METHODS: A human androgen dependent prostate cancer cell line LNCaP (AD) and its sub-line LNCaP (AI), i.e. androgen independent but overexpressing AR, were exposed to PEITC. The effects of PEITC on cell growth and AR expression/transcription were analyzed with MTT assay, real-time PCR and western blotting. The AR promoter activity was analyzed with the reporter activity after transfection with pAR-luc. The effects on Sp1, the major transcription factor of the AR, were tested with Sp1-luc activity, western blotting and electrophoretic mobility shift assay. RESULTS: PEITC induced a significant growth inhibition, with equal IC(50), in both AD and AI cells. The AR present in both cells was repressed as demonstrated with real-time PCR and western blot. PEITC mediates dual effects at transcriptional and post-translational levels to regulate the AR. At transcriptional level the AR level was reduced via inhibition of the transcription factor Sp1, and at post-translational level by accelerating protein degradation. CONCLUSION: PEITC represses AR transcription and expression, and mediates growth arrest in androgen dependent and independent prostate cancer cells. With the AR modulation and growth attenuation, PEITC and possibly other isothiocyanates, may prevent and inhibit hormone sensitive and refractory prostate cancer.

Androgen Receptor Antagonists↗

Suspended aggregates as an immobilization mode for high-density perfusion culture of HEK 293 cells in a stirred tank bioreactor.

Cells of the human embryonic kidney cell line (HEK 293) grown in repeated suspension and perfusion systems were characterized and described. Cell aggregates that formed immediately after the HEK 293 cells were inoculated in stirred vessels in serum-containing Dulbecco's modified Eagle's medium (D-MEM)/F-12 medium. The mean diameter of the cell aggregates reflecting the aggregate size increased with culture time, shifting from 63 to 239 mum after 1 and 8 days of culture in spinner flasks, respectively. No significant differences in cell performance were observed between HEK 293 cell populations grown as suspended aggregates and those grown as anchored monolayers. Replacing the D-MEM/F-12 with CD 293 medium caused the compact spherical cell aggregates to dissociate into single cells and small irregular aggregates without any apparent effect on cell performance. Moreover, the spherical cell aggregates could reform from individual cells and small aggregates when exposed to the serum-containing D-MEM/F-12 dominant medium. Perfusion culture of HEK 293 cells grown as suspended aggregates in a 7.5-l stirred tank bioreactor for 17 days resulted in a maximum viable cell density of 1.2 x 10(7) cells ml(-1). These results demonstrate the feasibility and proof-of-concept for using aggregates as an immobilization system in large-scale stirred bioreactors because a small-scale culture can be used as easily as the inoculum for larger bioreactors.

Bioreactors↗

Surface characteristics, mechanical properties, and cytocompatibility of oxygen plasma-implanted porous nickel titanium shape memory alloy.

Good surface properties and biocompatibility are crucial to porous NiTi shape memory alloys (SMA) used in medical implants, as possible nickel release from porous NiTi may cause deleterious effects in the human body. In this work, oxygen plasma immersion ion implantation (O-PIII) was used to reduce the amount of nickel leached from porous NiTi alloys with a porosity of 42% prepared by capsule-free hot isostatic pressing. The mechanical properties, surface properties, and biocompatibility were studied by compression tests, X-ray photoelectron spectroscopy (XPS), and cell culturing. The O-PIII porous NiTi SMAs have good mechanical properties and excellent superelasticity, and the amount of nickel leached from the O-PIII porous NiTi is much less than that from the untreated samples. XPS results indicate that a nickel-depleted surface layer predominantly composed of TiO(2) is produced by O-PIII and acts as a barrier against out-diffusion of nickel. The cell culturing tests reveal that both the O-PIII and untreated porous NiTi alloys have good biocompatibility.

Alloys↗

Genetic characterization and molecular mapping of a Hessian fly-resistance gene transferred from T. turgidum ssp. dicoccum to common wheat.

A gene (temporarily designated Hdic) conferring resistance to the Hessian fly (Hf) [Mayetiola destructor (Say)] was previously identified from an accession of German cultivated emmer wheat [Triticum turgidum ssp. dicoccum (Schrank ex Schübler) Thell] PI 94641, and was transferred to the Hf-resistant wheat germplasm KS99WGRC42. The inheritance of Hdic resistance exhibited incomplete penetrance because phenotypes of some heterozygous progenies are fully resistant and the others are fully susceptible. Five simple sequence repeat (SSR) markers (Xgwm136,Xcfa2153, Xpsp2999,Xgwm33, and Xbarc263) were linked to the Hdic gene on the short arm of wheat chromosome 1A in the same region as the H9, H10, and H11 loci. Flanking markers Xgwm33 and Xcfa2153 were mapped at distances 0.6 cM proximal and 1.4 cM distal, respectively. Marker analysis revealed that a very small intercalary chromosomal segment containing Hdic was transferred from emmer wheat to KS99WGRC42. This is the first emmer-derived Hf-resistance gene that has been mapped and characterized. The Hdic gene confers a high level of antibiosis to biotypes GP and L, as well as to strains vH9 and vH13 of the Hf, which is different from the biotype reaction patterns of the known Hf-resistance genes on chromosome 1A (H5 and H11 susceptible to biotype L, H9 and H10 susceptible to strain vH9). These results suggested that Hdic is either a new gene or a novel allele of a known H gene on chromosome 1A. The broad spectrum of resistance conferred by the Hdic gene makes it valuable for developing Hf resistant wheat cultivars.

Animals↗

Infrared-active vibrational modes of single-walled carbon nanotubes.

The IR-active vibrational modes of single-walled carbon nanotubes have been observed by optical transmission through thin films of bundled nanotubes. Because IR-active chemical functional groups, e.g., -COOH, -OH, might be attached to the tube walls and contribute additional spectral features, we have also studied the effects of chemical purification and long-term high-temperature vacuum annealing on the IR spectrum. Through comparison with theory, we are able to assign much of the sharp structure observed in our IR spectra.

Journal Article↗

Hessian fly resistance gene H13 is mapped to a distal cluster of resistance genes in chromosome 6DS of wheat.

H13 is inherited as a major dominant resistance gene in wheat. It was previously mapped to chromosome 6DL and expresses a high level of antibiosis against Hessian fly (Hf) [Mayetiola destructor (Say)] larvae. The objective of this study was to identify tightly linked molecular markers for marker-assisted selection in wheat breeding and as a starting point toward the map-based cloning of H13. Fifty-two chromosome 6D-specific microsatellite (simple sequence repeat) markers were tested for linkage to H13 using near-isogenic lines Molly (PI 562619) and Newton-207, and a segregating population consisting of 192 F(2:3) families derived from the cross PI 372129 (Dn4) x Molly (H13). Marker Xcfd132 co-segregated with H13, and several other markers were tightly linked to H13 in the distal region of wheat chromosome 6DS. Deletion analysis assigned H13 to a small region closely proximal to the breakpoint of del6DS-6 (FL 0.99). Further evaluation and comparison of the H13-linked markers revealed that the same chromosome region may also contain H23 in KS89WGRC03, an unnamed H gene (H(WGRC4)) in KS89WGRC04, the wheat curl mite resistance gene Cmc4, and a defense response gene Ppo for polyphenol oxidase. Thus, these genes comprise a cluster of arthropod resistance genes. Marker analysis also revealed that a very small intercalary chromosomal segment carrying H13 was transferred from the H13 donor parent to the wheat line Molly.

Animals↗

Possible association of the MAG locus with schizophrenia in a Chinese Han cohort of family trios.

Neurotransmitter-based hypotheses have so far led to only moderate success in predicting new pathogenetic findings in etiology of schizophrenia. On the other hand, the more recent oligodendroglia hypotheses of this disorder have been supported by an increasing body of evidence. For example, the expression level of the myelin associated glycoprotein (MAG) gene has been shown to be significantly lower in schizophrenia patient groups compared to control groups. Such an effect might be a result of genetic variations of the MAG gene. In order to test this hypothesis, we genotyped four markers within the MAG locus in 413 trios sample of the Han Chinese using allele-specific PCR. None of the four markers revealed noticeable allelic significance. However, the four-marker and two-marker haplotypes covering components rs720309 and rs720308 were observed to be significantly associated with schizophrenia (P < 0.0001) in this study. In addition, we identified one common risk haplotype TA (rs720309-rs720308, present in 78.5% of the general population) that showed increased evidence of overtransmission from parents to affected offspring (P = 0.0001). The results demonstrated MAG might play a role in genetic susceptibility to schizophrenia. Furthermore, our finding of a possible association between the MAG locus and schizophrenia is in agreement with the hypotheses of oligodendrltic and myelination dysfunction.

Adult↗

H9, H10, and H11 compose a cluster of Hessian fly-resistance genes in the distal gene-rich region of wheat chromosome 1AS.

H9, H10, and H11 are major dominant resistance genes in wheat, expressing antibiosis against Hessian fly [(Hf) Mayetiola destructor (Say)] larvae. Previously, H9 and H10 were assigned to chromosome 5A and H11 to 1A. The objectives of this study were to identify simple-sequence-repeat (SSR) markers for fine mapping of these genes and for marker-assisted selection in wheat breeding. Contrary to previous results, H9 and H10 did not show linkage with SSR markers on chromosome 5A. Instead, H9, H10, and H11 are linked with SSR markers on the short arm of chromosome 1A. Both H9 and H10 are tightly linked to flanking markers Xbarc263 and Xcfa2153 within a genetic distance of 0.3-0.5 cM. H11 is tightly linked to flanking markers Xcfa2153 and Xbarc263 at genetic distances of 0.3 cM and 1.7 cM. Deletion bin mapping assigned these markers and genes to the distal 14% of chromosome arm 1AS, where another Hf-resistance gene, Hdic (derived from emmer wheat), was also mapped previously. Marker polymorphism results indicated that a small terminal segment of chromosome 1AS containing H9 or H10 was transferred from the donor parent to the wheat lines Iris or Joy, and a small intercalary fragment carrying H11 was transferred from the resistant donor to the wheat line Karen. Our results suggest that H9, H10, H11, Hdic, and the previously identified H9- or H11-linked genes (H3, H5, H6, H12, H14, H15, H16, H17, H19, H28, and H29) may compose a cluster (or family) of Hf-resistance genes in the distal gene-rich region of wheat chromosome 1AS; and H10 most likely is the same gene as H9.

Animals↗

Real-time studies on microalgae under microgravity.

Using remote sensing technique, we investigated real-time Nostoc sphaeroides Kütz (Cyanobacterium) in Closed System under microgravity by SHENZHOU-2 spacecraft in January 2001. The experiments had 1 g centrifuges in space for control and ground control group experiments were also carried out in the same equipments and under the same controlled condition. The data about the population growth of Nostoc sp. of experiments and temperature changes of system were got from spacecraft every minute. From the data, we can find that population growth of Nostoc sp. in microgravity group was higher than that of other groups in space or on ground, even though both the control 1 g group in space and 1 g group on ground indicated same increasing characteristics in experiments. The growth rate of 1.4 g group (centrifuged group on ground) was also promoted during experiment. The temperature changes of systems are also affected by gravity and light. Some aspects about those differences were discussed. From the discussion of these results during experiment, it can be found that gravity is the major factor to lead to these changes.

Carbon Dioxide↗

Unique induction of p21(WAF1/CIP1)expression by vinorelbine in androgen-independent prostate cancer cells.

To study the mechanisms of the development of hormone refractory prostate cancer, we established an androgen-independent (AI) prostate cancer cell line derived from hormone-dependent (AD) LNCaP cells. Our previous studies have demonstrated that AI cells are deficient in expression of p21(WAFl/CIP1) (p21) due to overexpressed AR and are resistant to apoptosis. In this study, the induction of p53 and p21 expression by vinorelbine (Navelbine) was compared between AD and AI cells in an attempt to understand the difference(s) in apoptotic signalling pathways in these cells. Using a series of deletion of p21 reporter constructs, we found that vinorelbine mediated p21 induction in a p53-dependent manner in AD cells. In contrast, p21 expression restored by vinorelbine in AI cells was found to be through both p53-dependent and-independent pathways. In the absence of two p53 binding sites, Spl-3 and Spl-4 sites, in the promoter of human p21 gene, were found to be required for vinorelbine-mediated p21 activation. No p21 induction was observed by paclitaxel in AI cells. Exposure of AI cells to paciltaxel followed by vinorelbine produced synergism. Our data, thus, provide a basis for the synergistic combination of vinorelbine and paclitaxel for the treatment of advanced prostate cancer.

Androgen Antagonists↗

Density waves in traffic flow of two kinds of vehicles.

Through the car-following model, the traffic flow of two types of vehicles (cars and trucks) on a single-lane flow is studied, in which drivers on different vehicles have different sensitivities and the safety distance is assumed to be the same for all vehicles. The linear analysis is carried out to determine the condition of critical stability. With the nonlinear analysis, it proves that the small fluctuation of the vehicle density near the critical stable state satisfies the Korteweg-deVries equation and different sensitivities affect only the soliton evolution. When the headway in the critical state is more than the safety distance, the density around the soliton peak exceeds the density of the critical stable state, which can be explained as the formation of traffic jam. Contrarily, when the headway state is less than the safety distance, drivers will increase the headway to avoid the jam. The direct approach of the soliton perturbation shows that drivers' sensitivity will increase the soliton's amplitude continuously. Moreover, the increase of the number of trucks in the traffic flow will slow down the evolution of the amplitude.

Journal Article↗

Purification, characterization of two peptides from Buthus martensi Karch.

A new peptide named Martentoxin I and an analogue Martentoxin were purified and characterized from the venom of Buthus martensi Karch. Martentoxin I consisted of 36 amino acid residues with molecular mass as 3908.0 Da determined by matrix-assisted laser desorption ionization time-of-flight-MS. The amino acid sequence was determined as GLIDVKCFASSECWTACKKVTGSGQGKCQNNQCRCY by Edman degradation. Martentoxin consisted of 37 amino acid residues with a molecular mass as 4055.3 Da and it showed highly sequence identity to Martentoxin I as FGLIDVKCFASSECWTACKKVTGSGQGKCQNNQCRCY. Estimation from circular dichroism spectra indicated Martentoxin I owned 18.0% alpha-helix, 53.0% beta-sheet structure and 3.9% turn while Martentoxin contained 13.3% alpha-helix, 64.3% beta-sheet structure and 1.1% turn. The toxicity assay showed both peptides had no toxic effects on mice up to the dose of 10 mg/kg. Electrophysiological studies showed that Martentoxin I and Martentoxin at the concentration of 1 microm significantly inhibited voltage-dependent Na+ current (INa) and voltage-dependent delayed rectifier K+ current (IK) but had no effects on transient K+ current (IA). Both interactions with Na+ and K+ channels were irreversible.

Amino Acid Sequence↗

Mutation in Bmp7 exacerbates the phenotype of Bmp8a mutants in spermatogenesis and epididymis.

The specificity of bone morphogenetic proteins (BMPs) to their putative heteromeric receptor complexes in vivo is largely unclear. Closely related BMPs may use the same or different receptor complexes for signaling in a time- and space-dependent manner during development and differentiation. We have shown that Bmp7 expression in epididymal epithelium is developmentally regulated. Here, we further show that Bmp7 expression is also developmentally regulated in male germ cells. Bmp7 transcripts are detected in spermatogonia and early primary spermatocytes during early puberty and in stage-7 to -15 spermatids of the adult mice. Since Bmp7 homozygous mutants die perinatally and heterozygotes do not show obvious defects in the testis and the epididymis, the role of Bmp7 in spermatogenesis and epididymal function cannot be revealed by simply examining these mutants. Therefore, we have used a genetic approach by creating Bmp7/Bmp8a double mutants to investigate the role of Bmp7 in spermatogenesis and epididymal function. Here, we report that removal of one allele of Bmp7 exacerbates the phenotype of Bmp8a null mutants in spermatogenesis and epididymis of the adult. These indicate that, similar to Bmp8a, Bmp7 plays a role in both the maintenance of spermatogenesis and epididymal function and it further suggests that BMP8 and BMP7 signal through the same or similar receptors in these two systems.

Animals↗

Differential effect of vinorelbine versus paclitaxel on ERK2 kinase activity during apoptosis in MCF-7 cells.

The effects of vinorelbine and paclitaxel on the activity of extracellular signal-regulated protein kinase2 (ERK2), a member of MAP kinase, and its role in the induction of bcl-2 phosphorylation and apoptosis were evaluated in MCF-7 cells. We demonstrated that ERK2 was activated rapidly by vinorelbine, and was inhibited by either paclitaxel or estramustine. A 3-fold increase of ERK2 kinase activity was observed within 30 min when MCF-7 cells were treated with 0.1 microM vinorelbine. In contrast, the same treatment with paclitaxel resulted in a significant decrease of ERK2 kinase activity. We also demonstrated that elevated bcl-2 phosphorylation induced by vinorelbine is paralleled by decrease of a complex formation between bcl-2 and bax, cleavage of poly (ADP) ribose polymerase (PARP) protein, activation of caspase-7, and apoptosis. The levels of bcl-2 phosphorylation, bax, and PARP were not significantly affected by 2'-amino-3'-methoxyflavone (PD 98059), an ERK kinase specific inhibitor. Thus, our data suggest that the apoptosis induced by vinorelbine in MCF-7 cells is mediated through the bcl-2 phosphorylation/bax/caspases pathways, and that activation of ERK2 by vinorelbine does not directly lead to the drug-mediated apoptosis. Since decrease of PARP occurred quickly following the treatment of MCF-7 cells with either 0.1 microM of vinorelbine or paclitaxel, this protein may serve as an early indicator of apoptosis induced not only by DNA damaging agents, but also by antimicrotubule drugs.

Antineoplastic Agents, Phytogenic↗

Evidence for gliotoxin-glutathione conjugate adducts.

The equilibrium constant for the gliotoxin/glutathione pair was found to be 1200+/-100 M(-1) at pH 7.0 at 25 degrees C. Under conditions where the reaction was quenched rapidly with the addition of acid, gliotoxin-glutathione conjugate adducts were detected.

Chromatography, High Pressure Liquid↗

Anti-inflammatory and anti-ulcer activity of Calligonum comosum in rats.

The 10% ethanol extract of the aerial parts of Calligonum comosum (50--400 mg/kg, i.p.) significantly reduced the increase in hind paw oedema induced by carrageenan in rats. Following sub-acute oral administration of the extract (50 and 100 mg/kg, daily for 14 days), a significant anti-inflammatory activity in the cotton pellet model was observed. Pre-treatment with the extract (100, 200 and 400 mg/kg) produced a significant and dose-dependent inhibition to the acute gastric ulcers induced by phenylbutazone, indomethacin, 0.2 N NaOH and 80% ethanol.

Animals↗