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Biomedical subjects

D Xiao

Publications and source records attributed to D Xiao.

At least 19 recordsLinked to original sources

Fascin is a potential biomarker for early-stage oesophageal squamous cell carcinoma.

BACKGROUND: Fascin, an actin-binding protein, is usually expressed at a low level in normal epithelium, but is markedly up regulated in several types of carcinomas. Reports on fascin expression in oesophageal squamous cell carcinoma (ESCC) and precancerous lesions remain rare. AIM: To show the roles of fascin in the progression from normal epithelium to invasive ESCC. METHODS: Fascin expression in 102 sections embedded in paraffin wax, including samples of normal mucosa (n = 20), dysplasia (n = 10), ESCC (n = 62) and special sections (n = 10) of a full-length mucosa layer from the distant margin to the cancer focus of the excised oesophagus, and 49 fresh specimens of ESCC was analysed by immunohistochemistry, western blot and real-time reverse transcription-polymerase chain reaction. Fascin expression in ESCC cell lines was also investigated. RESULTS: In the immunohistochemical study, the positive rate of fascin was significantly higher in the tumour tissue than in the normal epithelium (p = 0.020), but no significant difference was shown between ESCC and dysplasia (p = 1.000). Immunostaining for fascin was only apparent in the basal layer of the normal epithelium. However, in the dysplasia, positive staining was observed in most of the heterogeneous cells from the basal layer to the granular layer of the epithelium. Fascin expression was seen to increase progressively from the normal epithelium to invasive ESCC. Up regulation of fascin was observed in 87.76% (43/49) and 77.55% (38/49) of the specimens, respectively, using western blot and real-time reverse transcription-polymerase chain reaction assays; 80% (4/5) of ESCC cell lines also expressed fascin at a high level. Furthermore, overexpression of fascin was markedly correlated with cell proliferation and lymph node metastasis. CONCLUSIONS: These findings suggested that fascin was associated with the transformation and development of ESCC and implicated the potential of fascin as a novel biomarker that would allow the tumour to be identified at an early stage in high-risk individuals.

Adult↗

Two-photon optical-beam-induced current solid-immersion imaging of a silicon flip chip with a resolution of 325 nm.

We report high-resolution subsurface imaging of a silicon flip chip by detection of the photocurrent generated by the two-photon absorption of 1530-nm light from a femtosecond Er:fiber laser. The technique combines the focal sensitivity of two-photon excitation with the enhanced optical resolution of high-numerical-aperture solid-immersion imaging. Features on a sub-1-microm scale are clearly resolvable with high contrast, showing a resolution of 325 nm.

Journal Article↗

Endorectal magnetic resonance imaging and spectroscopy for the detection of tumor foci in men with prior negative transrectal ultrasound prostate biopsy.

PURPOSE: We determined the ability of combined endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) to detect prostate cancer foci prospectively in men with prior negative transrectal ultrasound (TRUS) prostate biopsy. MATERIALS AND METHODS: Endorectal MRI with spectroscopy was performed in 24 consecutive patients with 1 or more prior negative TRUS prostatic biopsies for persistently increased prostate specific antigen and/or abnormal digital rectal examination. All studies were interpreted by a dedicated radiologist who reported areas of interest in the peripheral zone as normal, equivocal or suspicious on MRI and MRSI separately. Equivocal and suspicious areas were then correlated with a 3-dimensional prostate model. All patients underwent a standard TRUS 10-core peripheral zone biopsy with up to 4 additional biopsies targeted at the equivocal or suspected sites. RESULTS: Prostate cancer was detected in 7 of 24 subjects (29.2%). Considering the equivocal category as test negative the sensitivity, specificity, positive and negative predictive values, and the accuracy of MRI, MRSI and combined MRI/MRSI for the detection of prostate cancer were 57.1%, 57.1% and 100.0%, 88.2%, 82.4% and 70.6%, 66.7%, 57.1% and 58.3%, 83.3%, 82.1% and 100%, and 79.2%, 75.0% and 79.2%, respectively. The site of positive biopsy correlated correctly in 50% and 28.6% of MRI and MRSI labeled suspicious cores, respectively. CONCLUSIONS: MRI and MRSI have the potential to identify cancer foci and direct TRUS in patients with a previous negative TRUS biopsy. Further, larger studies are required to quantify the amount of benefit.

Aged↗

The temporal resolution of neural codes: does response latency have a unique role?

This article reviews the nature of the neural code in non-human primate cortex and assesses the potential for neurons to carry two or more signals simultaneously. Neurophysiological recordings from visual and motor systems indicate that the evidence for a role for precisely timed spikes relative to other spike times (ca. 1-10 ms resolution) is inconclusive. This indicates that the visual system does not carry a signal that identifies whether the responses were elicited when the stimulus was attended or not. Simulations show that the absence of such a signal reduces, but does not eliminate, the increased discrimination between stimuli that are attended compared with when the stimuli are unattended. The increased accuracy asymptotes with increased gain control, indicating limited benefit from increasing attention. The absence of a signal identifying the attentional state under which stimuli were viewed can produce the greatest discrimination between attended and unattended stimuli. Furthermore, the greatest reduction in discrimination errors occurs for a limited range of gain control, again indicating that attention effects are limited. By contrast to precisely timed patterns of spikes where the timing is relative to other spikes, response latency provides a fine temporal resolution signal (ca. 10 ms resolution) that carries information that is unavailable from coarse temporal response measures. Changes in response latency and changes in response magnitude can give rise to different predictions for the patterns of reaction times. The predictions are verified, and it is shown that the standard method for distinguishing executive and slave processes is only valid if the representations of interest, as evidenced by the neural code, are known. Overall, the data indicate that the signalling evident in neural signals is restricted to the spike count and the precise times of spikes relative to stimulus onset (response latency). These coding issues have implications for our understanding of cognitive models of attention and the roles of executive and slave systems.

Action Potentials↗

Antiangiogenic potential of 10-hydroxycamptothecin.

To investigate the antiangiogenic potential of 10-hydroxycamptothecin (HCPT), the proliferation of human microvascular endothelial cells (HMEC) and seven human tumor cell lines were detected by SRB assay, and the endothelial cell migration and tube formation were assessed using two in vitro model systems. Also, inhibition of angiogenesis was determined with a modification of the chick embryo chorioallantoic membrane (CAM) assay in vivo. Morphological assessment of apoptosis was performed by fluorescence microscope. HCPT 0.313-5 micromol x L(-1) treatment resulted in a dose-dependent inhibition of proliferation, migration and tube formation in HMEC cells, and HCPT 6.25-25 nmol x egg(-1) inhibited angiogenesis in CAM assay. HCPT 1.25-5 micromol x L(-1) elicited typical morphological changes of apoptosis including condensed chromatin, nuclear fragmentation, and reduction in volume in HMEC cells. HCPT significantly inhibited angiogenesis both in vitro and in vivo at relatively low concentrations, and this effect was related with induction of apoptosis in HMEC cells. These results taken collectively suggest that HCPT may be a potent antiangiogenetic and cytotoxic drug and further investigation is warranted.

Angiogenesis Inhibitors↗

Total synthesis of a conformationally constrained didemnin B analog.

The total synthesis of a didemnin B analogue containing a conformationally constrained replacement for the isostatine moiety is reported. Synthetic highlights include an improved preparation of 2-hydroxy-3-cyclohexenecarboxylic acid and a new strategy for accessing the macrocycle.

Animals↗

The human gastrin-releasing peptide receptor gene structure, its tissue expression and promoter.

The human gastrin-releasing peptide receptor (hGRP-R) is aberrantly expressed in cancers of the colon, lung and prostate and mediates signals of cellular proliferation. However, the underlying mechanisms of aberrant and/or activation of hGRP-R expression are unknown. Therefore, a genomic clone is identified, the hGRP-R gene is characterized, and the hGRP-R promoter is defined. The protein coding region is divided into three exons and exon/intron splice sites occur in the proximal 2nd and distal 3rd intracellular loops of the receptor molecule. The hGRP-R locus extends over more than 27 kb and is assigned to the chromosomal band Xp22 by fluorescence in situ hybridization. With primer extension experiments, we demonstrate two major transcription start sites in gastrointestinal and breast cancer cells, located 43 and 36 bp downstream of a TTTAAA motif which is identified 407 to 402 bp upstream of the ATG start codon. The hGRP-R is found most abundantly expressed in the normal human pancreas, where four gene-specific transcripts can be detected by Northern blot analysis, whereas only two transcripts are detected in the human stomach and, very weakly, in the adrenal cortex and the brain. In contrast, the human GRP-R is not expressed in the normal human colon, lung, and prostate. Steady state hGRP-R mRNA can also be detected in some cultured cells from breast, lung, and duodenal cancer. Robust hGRP-R promoter activity is demonstrated in a duodenal carcinoma cell line that natively expresses the functional hGRP-R. Truncation studies suggest a CRE motif, located 112 bp upstream of the major transcription start site, is required to confer basal hGRP-R promoter activity in duodenal cancer cells. These studies provide the necessary data to further elucidate molecular mechanisms of aberrant hGRP-R expression in human cancers.

Blotting, Northern↗

Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle.

Modification of artemisinin structure led us to the discovery of a novel class of antitumor compounds. These artemisinin derivatives containing cyano and aryl groups showed potent antiproliferative effect in vitro against P388 and A549 cells. This activity was reflected in P388 murine leukemia by an accumulation of cells in G1 phase, and induction of apoptosis.

Animals↗

[Lys3]Didemnins as potential affinity ligands.

The synthesis and biological activity of N(epsilon)-Z-[Lys3]didemnin B are reported. This novel analogue retains antiproliferative, cytotoxic, and protein biosynthesis inhibition activities, but at reduced levels. This result suggests the use of [Lys3]didemnin derivatives as potential affinity probes for studying the molecular target(s) of the didemnin class of natural products.

Affinity Labels↗

Global dynamics of a ratio-dependent predator-prey system.

Recently, ratio-dependent predator-prey systems have been regarded by some researchers to be more appropriate for predator-prey interactions where predation involves serious searching processes. However, such models have set up a challenging issue regarding their dynamics near the origin since these models are not well-defined there. In this paper, the qualitative behavior of a class of ratio-dependent predator-prey system at the origin in the interior of the first quadrant is studied. It is shown that the origin is indeed a critical point of higher order. There can exist numerous kinds of topological structures in a neighborhood of the origin including the parabolic orbits, the elliptic orbits, the hyperbolic orbits, and any combination of them. These structures have important implications for the global behavior of the model. Global qualitative analysis of the model depending on all parameters is carried out, and conditions of existence and non-existence of limit cycles for the model are given. Computer simulations are presented to illustrate the conclusions.

Animals↗

Synthesis and cytotoxicity of artemisinin derivatives containing cyanoarylmethyl group.

A series of 12alpha-deoxoartemisinyl cyanoarylmethyl dicarboxylates (4a-4o), dicarboxylic acids 12alpha-deoxoartemisinyl ester cyanoarylmethyl amide (5a-5k), and dicarboxylic acids 12alpha-deoxoartemisinyl ester N-methylcyanoarylmethyl amide (6a-6l), showing moderate cytotoxicity against P388 and L1210 cells were prepared. They induced the significant accumulation of L1210 and P388 cells in the G1 phase of the cell cycle. This mechanism of action was quite different from that of the majority of cytotoxic compounds used in the chemotherapy of cancer. Compound 4b possessed better cytotoxicity than the other compounds.

Animals↗

Fluorometric study of the inclusion interaction of beta-cyclodextrin derivatives with tetraphenylporphyrin and its analytical application.

The effects of native beta-cyclodextrin (beta-CD) and four kinds of alkylated beta-cyclodextrin (beta-CDs), i.e. heptakis (2,6-di-O-isobutyl-beta-cyclodextrin) (I), heptakis (2,6-di-O-octyl-beta-cyclodextrin) (II), heptakis (2,6-di-O-dodecyl-beta-cyclodextrin) (III), and heptakis (2,6-di-O-hexadecyl-beta-cyclodextrin) (IV), on the fluorescence behaviors of tetraphenylporphyrin (TPP) are investigated. An obvious fluorescence enhancement is observed from TPP by using alkylated derivatives compared to that obtained in beta-CD aqueous or in water. A 114-N fluorescence emission intensity enhancement is found for the complex with 2,6-di-O-octyl-beta-cyclodextrin relative to the free analyte. The exact stoichiometric ratios and the formation constants of the inclusion complexes have been examined by application of curve fitting method. The linear calibration plots between fluorescence intensity and TPP concentration are determined in the 1.14 x 10(-8)-5.06 x 10(-6) mol l(-1) range.

Alkylation↗

Synchronous fluorescence and absorbance dynamic liquid drop sensor for cr(VI) determination at the femtomole level.

A novel synchronous fluorimetric and absorptiometric technique based on dynamic liquid drops coupled with flow injection is described for the determination of chromium(VI) in aqueous solutions. Drops formed continuously at the end of a quartz capillary tube serve as reactor and optical cell. The reaction between chromium(VI) and 3,3',5,5'-tetramethylbenzidine dichloride (TMB-d) results in a significant decrease in fluorescence and transmitted light intensity, proportional to the logarithm of the concentration of chromium(VI). The transmitted light and fluorescence emission are detected in counter and perpendicular positions of the excitation light by a photomultipler tube and photodiode, respectively. In HCl-NaOAc buffer solution (pH 3.29), the sensor has a wide linear calibration range of 2 x 10(-8)-1 x 10(-4) mol l(-1) chromium(VI) with an absolute mass detection limit of 12.88 fmol.

Calibration↗

Maternal cocaine administration during pregnancy induces apoptosis in fetal rat heart.

We have previously demonstrated that cocaine induces apoptosis in primary cultures of fetal rat cardiomyocytes. The current study was designed to determine whether cocaine administered to the mother during pregnancy induced apoptosis in fetal rat heart. Pregnant rats were treated with cocaine subcutaneously (30 and 60 mg/kg per day) starting at day 15 of gestation and were terminated at day 21. Cocaine produced a dose-dependent increase in apoptotic cell death in the fetal heart by 1.3-fold (30 mg/kg per day) and 2.4-fold (60 mg/kg per day) of the control level (1.99+/-0.15%). Cocaine-induced DNA fragmentation in the fetal heart showed characteristic apoptotic ladder. In accordance, cocaine dose-dependently increased activities of caspase-3, caspase-8, and caspase-9 in the fetal heart by 0.5-, 0.6-, and 0.6-fold, respectively, at 30 mg/kg per day, and by 3.3-, 2.9-, and 2.3-fold, respectively, at 60 mg/kg per day. In contrast, cocaine showed no effect on caspase activities in the maternal heart. Bcl-2 and Bax proteins were detected in fetal rat heart, with 2.2-fold higher expression of Bcl-2 than Bax. Cocaine significantly increased Bax protein levels and decreased Bcl-2 protein levels, leading to a 7.5-fold increase in the Bax-to-Bcl-2 ratio in fetal rat heart. We conclude that cocaine causes apoptosis in fetal rat heart in vivo by upregulating the Bax-to-Bcl-2 ratio and increasing caspase activities, which is likely to play an important role in the adverse effects of cocaine on heart development.

Animals↗

Upregulation of eNOS in pregnant ovine uterine arteries by chronic hypoxia.

We tested the hypothesis that chronic high-altitude (3,820 m) hypoxia during pregnancy was associated with the upregulation of endothelial nitric oxide (NO) synthase (eNOS) protein and mRNA in ovine uterine artery endothelium and enhanced endothelium-dependent relaxation. In pregnant sheep, norepinephrine-induced dose-dependent contractions were increased by removal of the endothelium in both control and hypoxic uterine arteries. The increment was significantly higher in hypoxic tissues. The calcium ionophore A23187-induced relaxation of the uterine artery was significantly enhanced in hypoxic compared with control tissues. However, sodium nitroprusside- and 8-bromoguanosine 3',5'-cyclic monophosphate-induced relaxations were not changed. Accordingly, chronic hypoxia significantly increased basal and A23187-induced NO release. Chronic hypoxia increased eNOS protein and mRNA levels in the endothelium from uterine but not femoral or renal arteries. In nonpregnant animals, chronic hypoxia increased eNOS mRNA in uterine artery endothelium but had no effects on eNOS protein, NO release, or endothelium-dependent relaxation. Chronic hypoxia selectively augments pregnancy-associated upregulation of eNOS gene expression and endothelium-dependent relaxation of the uterine artery.

Altitude Sickness↗

Pregnancy enhances endothelium-dependent relaxation of ovine uterine artery: role of NO and intracellular Ca(2+).

The present study tested the hypothesis that the pregnancy-associated increase in endothelium-dependent relaxation of the uterine artery was mediated primarily by an increase in nitric oxide (NO) release, resulting in a reduction in smooth muscle intracellular Ca(2+) concentration ([Ca(2+)](i)). Uterine arteries obtained from nonpregnant and near-term (140 days gestation) pregnant sheep were used. The Ca(2+) ionophore A23187 induced endothelium-dependent relaxations in both nonpregnant and pregnant uterine arteries, with an increased relaxation in the pregnant tissue. In contrast, endothelium-independent relaxations induced by sodium nitroprusside were the same in nonpregnant and pregnant arteries. In addition, removal of the endothelium significantly increased noradrenaline-induced contractions in pregnant, but not nonpregnant, uterine arteries. In accordance, pregnancy increased both basal and A23187-stimulated NO releases in the uterine artery. Simultaneous measurement of tension and [Ca(2+)](i) in the smooth muscle demonstrated a linear correlation with the slope of unity between A23187-induced relaxation and the reduction of [Ca(2+)](i) in both nonpregnant and pregnant uterine arteries. The A23187-induced reduction of [Ca(2+)](i) was significantly enhanced in pregnant, compared with nonpregnant, uterine arteries. The results indicate that pregnancy increases NO release, which, through decreasing [Ca(2+)](i) in the smooth muscle, accounts for the increased endothelium-dependent relaxation of the uterine artery. Signal transduction pathways distal to NO production are not changed by pregnancy.

Animals↗

Studies on constituents from Chamaecyparis pisifera and antibacterial activity of diterpenes.

In the course of our research for biologically active constituents from coniferous plants, a chromone derivative (1) and an abietane derivative (2) were isolated along with several diterpenes from Chamaecyparis pisifera. Structures of the new compounds were determined to be 5,7-dihydroxy-2-(1-acetyl-2-methoxycarbonylethyl)-chromone and rel-(8R,10R,20S)-8,10,20-trihydroxy-9(10-->20)-abeo-abieta-9,13-dien-12-one by means of spectral methods including two-dimensional NMR experiments. Some of these abietane-type compounds isolated from this plants showed antibacterial activitv against the gram-positive bacteria Staphylococcus aureus and Bacillus subtilis.

Anti-Bacterial Agents↗

Ultrasensitive optical DNA biosensor based on surface immobilization of molecular beacon by a bridge structure.

A novel biotinylated molecular beacon (MB) probe was developed to prepare a DNA biosensor using a bridge structure. MB was biotinylated at the quencher side of the stem and linked on a biotinylated glass cover slip through streptavidin, which acted as a bridge between MB and glass matrix. An efficient fluorescence microscope system was constructed to detect the fluorescence change caused by the conformation change of MB in the presence of complementary DNA target. The proposed biosensor was used to directly detect, in real-time, the target DNA molecules. The bridge immobilization method caused the proposed DNA biosensor to have a faster and more stable response. Under the optimal conditions, the newly developed DNA biosensor showed a linear response toward ssDNA in the range of 5-100 nM with a detection limit of 2 nM. It was interesting to note that the described biosensor was reproducible after being regenerated by urea.

Biosensing Techniques↗