Biomedical subjects

Qiang Wu

Publications and source records attributed to Qiang Wu.

At least 19 recordsLinked to original sources

PubMed2026

Evaluation of a rapid-release mitomycin C-loaded porous microcapsule formulation (MitoCap) in a human urothelium-tumour model.

Intravesical mitomycin C (MMC) is limited by short bladder exposure and incomplete delivery to residual tumour tissue. We developed MitoCap, a porous MMC-loaded microcapsule formulation, and evaluated its formulation properties and antitumour performance in a human three-dimensional urothelium-tumour model (3D-UHU-TU). Microcapsules were produced by electrohydrodynamic atomisation using 2% or 5% poly(lactic-co-glycolic acid) (PLGA). Compared with 5% PLGA, the 2% formulation generated smaller microcapsules (2.90 ± 0.30 versus 4.03 ± 0.81 µm), greater apparent surface porosity and faster MMC release, with approximately 60% released within 15 min. The 2% formulation achieved an MMC loading capacity of 4.99 ± 0.16% (w/w), corresponding to 95.78 ± 3.09% recovery relative to the theoretical loading, and was selected for biological evaluation. The 3D-UHU-TU model integrates RT112 or T24 bladder cancer spheroids into a differentiated, urine-tolerant human urothelium, enabling tumour and urothelial responses to be assessed within the same construct. FITC-loaded microcapsules increased fluorescent model cargo signal within tumour regions compared with equivalent free FITC. Following 1 h apical exposure and 72 h recovery, MitoCap increased tumour-associated cleaved caspase-3 and tumour cell death relative to dose-matched free MMC. Tumour cell death increased from 62.3 ± 7.9% to 94.2 ± 1.3% in RT112 models and from 36.6 ± 4.7% to 52.8 ± 4.8% in T24 models, without increasing urothelial cell death relative to dose-matched free MMC. These findings support MitoCap as a rapid-release intravesical MMC formulation and demonstrate the value of compartment-resolved human urothelium-tumour models for evaluating local drug delivery.

Bladder cancer↗

PubMed2026

Stromal Hedgehog Signaling Drives Segment-Specific Malignant Transformation of Gastrointestinal Stem Cells by Producing Bone Morphogenetic Protein Antagonists.

BACKGROUND & AIMS: Hedgehog signaling plays a complex role in epithelial-stromal interactions, but its effects on gastrointestinal stem cells mediated by heterogeneous stromal cell populations remain incompletely defined. Here, we investigate how stromal Hedgehog signaling regulates gastric stem cells and tumorigenesis in a segment-specific manner. METHODS: We genetically activated Hedgehog signaling in distinct stromal cell lineages using Col1a2-, Pdgfra-, Gli1-, Acta2-, and Prrx1-CreERT mouse lines, combined with lineage tracing, RNA sequencing, chromatin immunoprecipitation-quantitative polymerase chain reaction, and pharmacologic interventions. Human gastric cancer data from The Cancer Genome Atlas were also analyzed. RESULTS: We show that genetic activation of Hedgehog signaling in stromal cells marked by Col1a2, Pdgfra, or Gli1, but not by Acta2, induces tumorigenesis in the stomach and gastroesophageal junction, but not in the small or large intestine. Hedgehog signaling increases the expression of multiple bone morphogenetic protein antagonists in gastric but not colonic stromal cells, via Gli1-mediated transcription. These bone morphogenetic protein antagonists, in turn, activate Wnt/β-catenin signaling in gastric stem cells, driving their proliferation and initiating gastric cancer expressing CD44 and Sox9, but not Lgr5. Activating bone morphogenetic protein or inhibiting Wnt signaling blocks tumor initiation. Analysis of patient data from The Cancer Genome Atlas reveals elevated Hedgehog signaling in gastric cancers, which correlates with suppressed bone morphogenetic protein signaling. CONCLUSIONS: These findings uncover a gastrointestinal segment-specific oncogenic role for Hedgehog signaling in Col1a2+Acta2- stromal cells, mediated through the bone morphogenetic protein-Wnt-β-catenin axis.

BMP Antagonists↗

PubMed2007

Primary visual cortex volume and total neuron number are reduced in schizophrenia.

A number of studies that assessed the visual system in subjects with schizophrenia found impairments in early visual processing. Furthermore, functional imaging studies suggested changes in primary visual cortex activity in subjects with schizophrenia. Interestingly, postmortem studies of subjects with schizophrenia reported an increased density of neurons in the primary visual cortex (Brodmann's area 17, BA17). The observed changes in visual processing may thus be reflected in structural changes in the circuitry of BA17. To characterize the structural changes further we used stereological methods based on unbiased principles of sampling (Cavalieri's principle and the optical fractionator) to estimate the total volume and neuron number of BA17 in postmortem brains from 10 subjects with schizophrenia and 10 matched normal comparison subjects. In addition, we assessed cortical thickness. We found a marked and significant reduction in total neuron number (25%) and volume (22%) of BA17 in the schizophrenia group relative to the normal comparison subjects. In contrast, we found no changes in neuronal density or cortical thickness between the two groups. Subjects with schizophrenia therefore have a smaller cortical area allocated to primary visual perception. This finding suggests the existence of a schizophrenia-related change in cortical parcellation.

Adult↗

PubMed2006

Sequence analysis and expression mapping of the rat clustered protocadherin gene repertoires.

Three closely-linked clusters of protocadherin (Pcdh) genes (alpha, beta, and gamma) encoding more than 50 distinct mRNAs have been identified in humans and mice, and proposed to play important roles in neuronal connectivity in the CNS. The human and mouse Pcdh alpha and gamma clusters each span a region of about 300 kb genomic DNA, and are each organized into a tandem array of more than a dozen highly-similar "variable" exons, and three downstream "constant" exons. Little is known about the expression patterns of the alpha and gamma repertoires in the CNS. Here, we comprehensively analyzed the one megabase rat Pcdh genomic DNA sequences at the nucleotide level using various computational methods. We found that the clustered rat Pcdh genes display strict orthologous relationships with those of mice but not humans. Moreover, each rat Pcdh variable exon is preceded by a distinct promoter. We designed two complete sets of isoform-specific probes and extensively mapped the expression patterns for each member of the alpha and gamma repertoires in the adult rat CNS by non-isotopic in situ hybridization experiments. We found that most alpha and gamma mRNA isoforms are broadly expressed in similar patterns in subsets of cells (with some displaying interesting cortical layer-specific expression) throughout various CNS regions, including the olfactory bulb, cerebral cortex, hippocampus, cerebellum, and spinal cord. The broad expression of most alpha or gamma mRNAs throughout various regions of the CNS is consistent with the hypothesis that these genes may be used for neurons to establish their individuality and also provide the adhesive diversity required for complex synaptic connectivity in the mammalian CNS.

Animals↗

PubMed2006

Description of the cardiac movement using hexagonal image structures.

The most notable characteristic of the heart is its movement. Detection of dynamic information describing cardiac movement such as amplitude, speed and acceleration facilitates interpretation of normal and abnormal function. In recent years, the Omni-directional M-mode Echocardiography System (OMES) has been developed as a process that builds moving information from a sequence of echocardiography image frames. OMES detects cardiac movement through construction and analysis of Position-Time Grey Waveform (PTGW) images on some feature points of the boundaries of the ventricles. Image edge detection plays an important role in determining the feature boundary points and their moving directions as the basis for extraction of PTGW images--Spiral Architecture (SA) has proved efficient for image edge detection. SA is a hexagonal image structure in which an image is represented as a collection of hexagonal pixels. There are two operations called spiral addition and spiral multiplication defined on SA. They correspond to image translation and rotation, respectively. In this paper, we perform ventricle boundary detection based on SA using various defined chain codes. The gradient direction of each boundary point is determined at the same time. PTGW images at each boundary point are obtained through a series of spiral additions according to the directions of boundary points. Unlike the OMES system, our new approach is no longer affected by the translation movement of the heart. As its result, three curves representing the amplitude, speed and acceleration of cardiac movement can be easily drawn from the PTGW images obtained. Our approach is more efficient and accurate than OMES, and our results contain a more robust and complete description of cardiac motion.

Algorithms↗

PubMed2006

Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys.

Both in vivo and post-mortem investigations have demonstrated smaller volumes of the whole brain and of certain brain regions in individuals with schizophrenia. It is unclear to what degree such smaller volumes are due to the illness or to the effects of antipsychotic medication treatment. Indeed, we recently reported that chronic exposure of macaque monkeys to haloperidol or olanzapine, at doses producing plasma levels in the therapeutic range in schizophrenia subjects, was associated with significantly smaller total brain weight and volume, including an 11.8-15.2% smaller gray matter volume in the left parietal lobe. Consequently, in this study we sought to determine whether these smaller volumes were associated with lower numbers of the gray matter's constituent cellular elements. The use of point counting and Cavalieri's principle on Nissl-stained sections confirmed a 14.6% smaller gray matter volume in the left parietal lobe from antipsychotic-exposed monkeys. Use of the optical fractionator method to estimate the number of each cell type in the gray matter revealed a significant 14.2% lower glial cell number with a concomitant 10.2% higher neuron density. The numbers of neurons and endothelial cells did not differ between groups. Together, the findings of smaller gray matter volume, lower glial cell number, and higher neuron density without a difference in total neuron number in antipsychotic-exposed monkeys parallel the results of post-mortem schizophrenia studies, and raise the possibility that such observations in schizophrenia subjects might be due, at least in part, to antipsychotic medication effects.

Algorithms↗

PubMed2006

Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1.

Embryonic stem (ES) cells are pluripotent cells that can self-renew or differentiate into many cell types. A unique network of transcription factors and signalling molecules are essential for maintaining this capability. Here, we report that a spalt family member, Sall4, is required for the pluripotency of ES cells. Similarly to Oct4, a reduction in Sall4 levels in mouse ES cells results in respecification, under the appropriate culture conditions, of ES cells to the trophoblast lineage. Sall4 regulates transcription of Pou5f1 which encodes Oct4. Sall4 binds to the highly conserved regulatory region of the Pou5f1 distal enhancer and activates Pou5f1 expression in vivo and in vitro. Microinjection of Sall4 small interfering (si) RNA into mouse zygotes resulted in reduction of Sall4 and Oct4 mRNAs in preimplantation embryos and significant expansion of Cdx2 expression into the inner cell mass. These results demonstrate that Sall4 is a transcriptional activator of Pou5f1 and has a critical role in the maintenance of ES cell pluripotency by modulating Oct4 expression. The data also indicates that Sall4 is important for early embryonic cell-fate decisions.

Animals↗

PubMed2006

Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cells with self-renewing property. Nanog is a homeobox transcription factor required to maintain ES cells in a non-differentiated state. Using affinity purification coupled to liquid chromatography-tandem mass spectrometry analysis, we identified Sall4 as a Nanog co-purified protein. Co-immunoprecipitation and glutathione S-transferase pulldown experiments confirmed the interaction between Nanog and Sall4. We showed that Nanog and Sall4 co-occupied Nanog and Sall4 enhancer regions in living ES cells. Knockdown of Nanog or Sall4 by RNA interference led to a reduction in Nanog and Sall4 enhancer activities, providing evidence that these factors are positively regulating these enhancers. Importantly, co-transfection of Sall4 with these ES cell-specific enhancers led to transactivation in heterologous somatic cells. Chromatin immunoprecipitation experiments also showed that Sall4 co-occupied many Nanog binding sites in ES cells. Our data implicate Sall4 as an important component of the transcription regulatory networks in ES cells by cooperating with Nanog. We suggest that Sall4 and Nanog form a regulatory circuit similar to that of Oct4 and Sox2. This study highlights the extensive regulatory loops connecting genes, which encode for key transcription factors in ES cells.

Animals↗

PubMed2006

Conformational analysis of sulfate species on Ag/Al2O3 by means of theoretical and experimental vibration spectra.

The formation and configuration of sulfate species on Ag/Al2O3 were studied by means of in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations. The comparison between theoretical and experimental vibration spectra enable us to draw the following conclusions: Bidentate sulfate species rather than tridentate sulfate species are the predominant surface species on Ag/Al2O3. Moreover, both bidentate and tridentate sulfate species may coexist on the catalyst surface at a lower coverage. The accumulation of surface sulfate species could well explain the blue shift of the sulfate species in IR spectra. In addition, the in situ DRIFTS could distinguish between the sulfate species that linked to Al site and Ag site, which was well supported by temperature-programmed desorption (TPD) results.

Journal Article↗

PubMed2006

Prevention of hepatic injury by a traditional Chinese formulation, BJ-JN, in mice treated with Bacille-Calmette-Guérin and lipopolysaccharide.

The hepatoprotective effects of BJ-JN (a traditional Chinese formulation) were evaluated in Bacille-Calmette-Guérin and lipopolysaccharide (BCG/LPS)-induced immunological liver injury (ILI) in mice. BJ-JN (0.75, 1.5, 3 g/kg) was administered via gavage daily for 10 days. Liver index (liver weight/body weight), serum levels of alanine aminotransferase (ALT), hepatic nitric oxide (NO), malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, splenocyte proliferation, production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) by peritoneal macrophages, and histopathologic changes of the liver were evaluated following the 10 days treatment. BJ-JN (0.75, 1.5, 3 g/kg) effectively reduced the BCG/LPS-induced elevated liver index, serum ALT levels, hepatic NO and MDA content, and restored hepatic SOD activity in ILI mice. BJ-JN treatment also alleviated diminished splenocyte proliferation induced by concanavalin A (ConA) and repressed abnormally high levels of TNF-alpha and IL-1 from peritoneal macrophages. The histopathological analysis suggested that BJ-JN reduced the degree of liver injury of ILI mice. These results suggest that BJ-JN has a protective and therapeutic effect on ILI mice, which might be associated with its antioxidant properties, ability to reduce NO production and immunoregulatory function.

Alanine Transaminase↗

PubMed2006

The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.

Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells. Using the chromatin immunoprecipitation paired-end ditags method, we mapped the binding sites of these factors in the mouse ES cell genome. We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively. Comparative location analyses indicated that Oct4 and Nanog overlap substantially in their targets, and they are bound to genes in different configurations. Using de novo motif discovery algorithms, we defined the cis-acting elements mediating their respective binding to genomic sites. By integrating RNA interference-mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors can activate or suppress transcription. We further showed that common core downstream targets are important to keep ES cells from differentiating. The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination.

Animals↗

PubMed2006

Somal size of immunolabeled pyramidal cells in the prefrontal cortex of subjects with schizophrenia.

BACKGROUND: Although the somal volume of Nissl-stained deep layer 3 pyramidal cells is reduced in prefrontal cortex area 9 of subjects with schizophrenia, the subset of large pyramidal cells immunoreactive (IR) for nonphosphorylated neurofilament protein (NNFP) is not. Consequently, we hypothesized that the somal volume of another subset of pyramidal cells immunoreactive for neuronal calcium binding protein-1 (Necab-1) is significantly reduced in schizophrenia. METHODS: We labeled Necab-1-IR pyramidal neurons using immunoperoxidase techniques and estimated the mean somal volume in deep layer 3 of area 9 in 13 matched pairs of control and schizophrenic subjects. Identical studies were conducted for pyramidal neurons immunoreactive for neuronal nuclear protein (Neu-N), which is present in all neurons. RESULTS: In subjects with schizophrenia, neither the mean somal volume of Necab-1-IR pyramidal neurons nor of Neu-N-IR pyramidal neurons was significantly different from control subjects. In addition, the mean somal volume of Neu-N-IR cells was larger than that of Nissl-stained cells in both subject groups, and the magnitude of this difference was greater for the subjects with schizophrenia. CONCLUSIONS: These findings suggest that immunoperoxidase techniques are associated with an overestimation of the volume of labeled neurons. This confound appears to interact with disease state, and thus obscures differences between diagnostic groups.

Adult↗

PubMed2006

Functional characterization of Zn2(+)-sensitive GABA transporter expressed in primary cultures of astrocytes from rat cerebral cortex.

The extracellular levels of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the mammalian cerebral cortex, are regulated by specific high-affinity Na(+)/Cl(-) dependent transporters (GATs). GAT1 mainly expressed in cerebrocortical neurons is thought to play an important role for clearance of GABA in the extracellular fluid, whereas there is a little information available for pharmacological importance for astrocytic GABA transporters. In the present study, we therefore described the functional characterization of GABA transport in primary cultures of astrocytes from rat cerebral cortex and the identification of GABA transporter subtype(s). GABA transport was Na(+) and Cl(-) dependent and saturable with a Michaelis constant (K(t)) of 9.3+/-2.8 microM. Na(+)- and Cl(-)- activation kinetics revealed that the Na(+)-Cl(-)-to-GABA stoichiometry was 2:1:1 and concentrations of Na(+) and Cl(-) necessary for half-maximal transport (K(0.5)(Na) and K(0.5)(Cl)) were 78+/-28 mM and 9.6+/-2.6 mM, respectively. Na(+)-dependent GABA transport was competitively inhibited by various GABA transport inhibitors, especially GAT2- or GAT3-selective inhibitor. In addition, Zn(2+), which has been reported to be a potent inhibitor of GAT3, was found to have a significantly but partially inhibitory effect on the Na(+)-dependent GABA transport in a concentration-dependent manner. Furthermore, reverse transcription-PCR and Western blot analyses revealed that GAT2 and GAT3 are expressed in primary cultures of astrocytes. These results clearly showed that zinc is a useful reagent for separating GAT3 activity from GAT1- and GAT2-activities in CNS. To our knowledge, the present study represents the first report on the inhibitory effect of zinc on the Na(+)-dependent GABA transport in rat cerebrocortical astrocytes.

Animals↗

PubMed2006

Functional expression of metabotropic GABAB receptors in primary cultures of astrocytes from rat cerebral cortex.

GABA(B) receptor subunits are widely expressed on neurons throughout the central nervous system (CNS), at both pre- and postsynaptic sites, where they mediate the late and slow component of the inhibitory response to the major inhibitory neurotransmitter GABA. Recently, GABA(B) receptors have been reported to be expressed in astrocytes and microglia in the rat CNS by immunocytochemistry. However, there are few reports available for the functional characterization of GABA(B) receptors on astrocytes. In the present study, we therefore investigated the functional expression and characteristics of GABA(B) receptors in primary cultures of astrocytes from rat cerebral cortex. In the presence of 10 microM GTP, forskolin concentration-dependently increased adenylylcyclase (AC) activity in membranes prepared from rat astrocytes. The selective GABA(B) agonist (R)-baclofen concentration-dependently reduced forskolin-stimulated AC activity in the presence of 10 microM GTP. This effect was reversed by the selective GABA(B) antagonists, CGP-55845 and CGP-54626, and was completely abolished by treatment of astrocytic membranes with pertussis toxin. In addition, RT-PCR, Western blotting, and immunocytochemistry clearly showed that metabotropic GABA(B) receptor isoforms (GABA(B)R1 and GABA(B)R2) are expressed in rat cerebrocortical astrocytes. Taken collectively, these results demonstrate that functionally active metabotropic GABA(B) receptors are expressed in rat cerebrocortical astrocytes.

Adenylyl Cyclase Inhibitors↗

PubMed2006

A global map of p53 transcription-factor binding sites in the human genome.

The ability to derive a whole-genome map of transcription-factor binding sites (TFBS) is crucial for elucidating gene regulatory networks. Herein, we describe a robust approach that couples chromatin immunoprecipitation (ChIP) with the paired-end ditag (PET) sequencing strategy for unbiased and precise global localization of TFBS. We have applied this strategy to map p53 targets in the human genome. From a saturated sampling of over half a million PET sequences, we characterized 65,572 unique p53 ChIP DNA fragments and established overlapping PET clusters as a readout to define p53 binding loci with remarkable specificity. Based on this information, we refined the consensus p53 binding motif, identified at least 542 binding loci with high confidence, discovered 98 previously unidentified p53 target genes that were implicated in novel aspects of p53 functions, and showed their clinical relevance to p53-dependent tumorigenesis in primary cancer samples.

Binding Sites↗

PubMed2006

[Relationship between adiponectin and beta-cell function in abdominal visceral obesity women].

OBJECTIVE: To investigate the relationship between adiponectin and beta-cell function in abdominal visceral obesity women. METHODS: Nine abdominal visceral obesity women (VO), 9 normal subjects (C) and 7 patients with type 2 diabetes mellitus (T2DM) were enrolled in the study. Beta-cell function and insulin sensitivity were determined by hyperglycemic clamp, fasting serum adiponectin was assayed by ELISA and regional body fat was measured by MRI. RESULT: The levels of first phase insulin release (FPIR), glucose disposal rates (GDR), insulin sensitivity index (ISI) and adiponectin were significantly elevated in control group compared with VO group and T2DM group. As compared with T2DM group, the levels of adiponectin, FPIR, second phase insulin release (SPIR) and maximum insulin release (INS(max)) increased significantly in VO group. Multiple stepwise regression analysis showed that age, FPIR and GDR were positively correlated to adiponectin (B=0.145, 0.194, 0.277 respectively, all P<0.05), while waist-hip ratio was negatively correlated with adiponectin (B=-7.424, P<0.05). CONCLUSION: The visceral obesity women have lower adiponectin levels, and hyperadiponectinemia may be the link with insulin secretion.

Abdominal Fat↗

PubMed2006

[Effects of anti-HER-2 chimeric antibody chA21 on proliferative inhibition of SKOV3 cells and inducing their apoptosis].

AIM: To explore the effects of anti-HER-2 chimeric antibody chA21 on proliferation and apoptosis of ovarian cancer cell lines SKOV3. METHODS: MTT colorometric assay, HE staining, transmission electron microscopy, flow cytometry and TUNEL staining were used to study the proliferative inhibition and apoptotic induction of SKOV3 cells by chA21 in vitro. RESULTS: Proliferative inhibition rate and apoptotic rate of SKOV3 cells were increased with dose and action time by chA21 (0.2 mg/L-5.4 mg/L). CONCLUSION: chA21 can remarkably inhibit proliferation of SKOV3 cells in vitro and induction of apoptosis may be a principal way.

Antibodies↗

PubMed2006

[The role of four natures of medicine in acupoint sticking therapy].

OBJECTIVE: To investigate the effect of four natures of medicine on therapeutic effect of acupoint sticking therapy. METHODS: Sixty-one cases of primary dysmenorrhea were randomly divided into a capsaicin group (n=20), a menthol group (n=20) and a control group (n=21). They were treated respectively with capsaicin and menthol, which are extracts of Lajiao (Fructus Capsici) and Bohe (Herba Menthae) with same pungent in flavor and different cold (cool) and heat in property, and application of Tongjing Jiu Tieji (plaster for dysmenorrhea) at Shenque (CV 8). Changes of clinical symptoms before and after treatment were observed. RESULTS: After treatment, the cumulative scores of symptoms and the scores of pain decreased significantly in the 3 groups (P < 0.01), with no significant differences among the 3 groups (P > 0.05). CONCLUSION: In acupoint sticking therapy, the four natures of medicine have no obvious effect on the therapeutic effect, so the four natures of medicine should not used as main standard of medicine selection.

Acupuncture Points↗