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Biomedical subjects

Bo Liu

Publications and source records attributed to Bo Liu.

At least 37 records · Page 2Linked to original sources
PubMed2006

Craniosynostosis caused by Axin2 deficiency is mediated through distinct functions of beta-catenin in proliferation and differentiation.

Targeted disruption of Axin2 in mice induces skeletal defects, a phenotype resembling craniosynostosis in humans. Premature fusion of cranial sutures, caused by deficiency in intramembranous ossification, occurs at early postnatal stages. Axin2 negatively regulates both expansion of osteoprogenitors and maturation of osteoblasts through its modulation on Wnt/beta-catenin signaling. We investigate the dual role of beta-catenin to gain further insights into the skull morphogenetic circuitry. We show that as a transcriptional co-activator, beta-catenin promotes cell division by stimulating its target cyclin D1 in osteoprogenitors. Upon differentiation of osteoprogenitors, BMP signaling is elevated to accelerate the process in a positive feedback mechanism. This Wnt-dependent BMP signal dictates cellular distribution of beta-catenin. As an adhesion molecule, beta-catenin promotes cell-cell interaction mediated by adherens junctions in mature osteoblasts. Finally, haploid deficiency of beta-catenin alleviates the Axin2-null skeletal phenotypes. These findings support a model for disparate roles of beta-catenin in osteoblast proliferation and differentiation.

Animals↗
PubMed2006

A micro-tomography method based on X-ray diffraction enhanced imaging for the visualization of micro-organs and soft tissues.

Diffraction enhanced imaging (DEI) is one of the phase contrast imaging methods using the monochromatic X-ray from synchrotron, which provides information on the out-of-plane angular deviation of X-ray. DEI allows the investigation of micro-structures inside weakly absorbing samples at high spatial resolution without serious radiation exposure. Tomographic techniques can be applied readily to phase contrast images. The combination of DEI and tomography allows for a reconstruction of refractive index gradient distribution inside weakly absorbing samples with micrometer resolution, particularly suited for the 3D observation of micro-organisms and tissues. The existing phase contrast tomography methods based on DEI use phase contrast images as projections, such images contain not only the phase information, but also the absorption information. A novel method (DEI in the tomography mode) was developed to greatly increase the proportion of refraction information in phase contrast images by computing the difference between the two sets of images acquired at different angles of the rocking curve to adopt the projections with a complete set (2pi) for reconstruction. The reconstructed images of cochlea of a guinea pig showed the spatial structures and the micro-features inside the samples. The new method reveals higher spatial resolution compared to the conventional phase contrast tomography methods and is more suitable to the investigation of micro-structures of micro-organisms and tissue materials.

Algorithms↗
PubMed2006

[Clinical contrast of cervical pedicle screw fixation assisted by C-arm fluoroscopy or 3D navigation system].

OBJECTIVE: To evaluate the feasibility and accuracy of cervical (C(2)-C(7)) pedicle screw fixation assisted by C-arm fluoroscopy or 3D navigation system (CT-based navigation system or Iso-C 3D navigation system). METHODS: One hundred and forty-five cervical pedicle screws inserted with C-arm fluoroscopy and 187 pedicle screws inserted with 3D navigation system were observed by postoperative CT or Iso-C 3D scan. The process of navigation was investigated. RESULTS: In the 145 screws inserted with C-arm fluoroscopy, 133 screws are accurate (91.7%), and in the 187 screws inserted by 3D navigation system, 183 screws are accurate (97.9%) (chi2 = 6.705, P = 0.010), and the 4 misplaced screws occurred in the early stage of navigation system application. The process of navigation was investigated in twenty-five patients. With CT-based navigation, the mean time for registration and surface matching was 3.5 minutes; with Iso-C 3D navigation, the mean time for images collection and transfer was 6.2 minutes. The mean time for screw-marker insertion was 2 minutes. CONCLUSIONS: 3D navigation system can increase accuracy of cervical pedicle screw fixation obviously.

Adult↗
PubMed2006

Characterization of the coupling of quantum dots and immunoglobulin antibodies.

Water-soluble quantum dots (QDs) were used to label goat anti-human immunoglobulin antibodies (Abs), and the labeling process was characterized by column purification. The QDs obtained in organic solvent were modified with mercaptoacetic acid (MAA) and became water-soluble. These water-soluble QDs were linked to the antibodies using the coupling reagents ethyl-3-(dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The linking process was shown to be effective by ultra-filter centrifugation and column purification. After comparing the quantities of Abs and water-soluble QDs involved in the linking reaction via column purification, it was found that a molar Abs:QD ratio of >1.2 resulted in most of the water-soluble QDs becoming covalently linked to the Abs. The circular dichroism (CD) spectra of Abs and QD-Ab conjugates were very similar to each other, indicating that the secondary structure of Abs remained largely intact after the conjugation. Finally, antigen (Ag)-antibody (Ab) recognition reactions perfomed on the surface of a glass slide showed that the conjugate retained the activity of Abs. This work lends support to the idea of linking biomolecules to QDs, and thus should aid the application of QDs to the life sciences.

Humans↗
PubMed2006

Impaired neural development caused by inducible expression of Axin in transgenic mice.

Ablations of the Axin family genes demonstrated that they modulate Wnt signaling in key processes of mammalian development. The ubiquitously expressed Axin1 plays an important role in formation of the embryonic neural axis, while Axin2 is essential for craniofacial skeletogenesis. Although Axin2 is also highly expressed during early neural development, including the neural tube and neural crest, it is not essential for these processes, apparently due to functional redundancy with Axin1. To further investigate the role of Wnt signaling during early neural development, and its potential regulation by Axins, we developed a mouse model for conditional gene activation in the Axin2-expressing domains. We show that gene expression can be successfully targeted to the Axin2-expressing cells in a spatially and temporally specific fashion. High levels of Axin in this domain induce a region-specific effect on the patterning of neural tube. In the mutant embryos, only the development of midbrain is severely impaired even though the transgene is expressed throughout the neural tube. Axin apparently regulates beta-catenin in coordinating cell cycle progression, cell adhesion and survival of neuroepithelial precursors during development of ventricles. Our data support the conclusion that the development of embryonic neural axis is highly sensitive to the level of Wnt signaling.

Journal Article↗
PubMed2006

Hemodynamic effects of potent and selective JNK inhibitors in anesthetized rats: implication for targeting protein kinases in metabolic diseases.

The hemodynamic effects of a series of potent and selective 4-aminopyridine carboxamide-based pan-JNK inhibitors were assessed in an anesthetized rat model. The effects of these agents on mean arterial pressure, heart rate, cardiac contractility, and peripheral vascular resistance are described, and the implication for targeting protein kinases in metabolic diseases is discussed.

Aminopyridines↗
PubMed2006

Regulation of the orphan receptor TR3 nuclear functions by c-Jun N terminal kinase phosphorylation.

The orphan receptor TR3 functions in the nucleus as a transcription factor to negatively or positively regulate gene expression. c-Jun N-terminal kinase (JNK) phosphorylation plays an important role in modulating the nuclear functions of TR3. Although TR3 is the phosphorylation target of JNK, the regulatory mechanism of JNK on TR3 functions remains to be elucidated. Here we showed that JNK activator anisomycin induced TR3 phosphorylation through JNK1 rather than p38 and ERK signals, which is mediated by its upstream factors MAPK kinase 4 and MAPK kinase 7. We also identified the exact phosphorylation site of JNK to be serine 95 at the N terminus of TR3, around which a classical JNK phosphorylation motif exists. Furthermore, we demonstrated that TR3 phosphorylation by JNK coincided with its ubiquitination and degradation, resulting in the loss of its mitogenic activity. Finally, we showed that JNK-induced phosphorylation blocked the DNA binding property of TR3 and hence diminished its transactivation activity. Taken together, our findings revealed a novel cross talk between TR3 and JNK signal pathway and shed light on the mechanism of JNK phosphorylation-dependent regulation on TR3 nuclear functions.

Cell Division↗
PubMed2006

Isolation and characterization of coactivator-binding peptoids from a combinatorial library.

Pharmacologic agents capable of activating the expression of specific genes would be valuable tools in biological research and could potentially be useful therapeutically. Efforts to develop a general solution to this problem have focused on the discovery of cell permeable mimics of native transcription factors comprised of linked DNA-binding and activation domain surrogates. Recently, we reported the isolation of a peptoid, called KBPo2, that binds a fragment of the mammalian coactivator CREB-binding protein (CBP). When delivered to a promoter-bound DNA-binding domain, this peptoid acted as a potent activation domain mimic in human cells. In this paper, we provide full details of the screening experiments and also report further characterization of this molecule as well as the other peptoids that came out of the screen. Of the three peptoids identified as putative CBP ligands, only KBPo2 demonstrated the necessary combination of binding affinity, specificity and cell permeability necessary to function as a potent activation domain mimic in cells. KBPo2 binds to CBP in a region different than that recognized by the native activation peptide from the transcription factor CREB.

CREB-Binding Protein↗
PubMed2006

A key role for STIM1 in store operated calcium channel activation in airway smooth muscle.

BACKGROUND: Control of cytosolic calcium plays a key role in airway myocyte function. Changes in intracellular Ca2+ stores can modulate contractile responses, modulate proliferation and regulate synthetic activity. Influx of Ca2+ in non excitable smooth muscle is believed to be predominantly through store operated channels (SOC) or receptor operated channels (ROC). Whereas agonists can activate both SOC and ROC in a range of smooth muscle types, the specific trigger for SOC activation is depletion of the sarcoplasmic reticulum Ca2+ stores. The mechanism underlying SOC activation following depletion of intracellular Ca2+ stores in smooth muscle has not been identified. METHODS: To investigate the roles of the STIM homologues in SOC activation in airway myocytes, specific siRNA sequences were utilised to target and selectively suppress both STIM1 and STIM2. Quantitative real time PCR was employed to assess the efficiency and the specificity of the siRNA mediated knockdown of mRNA. Activation of SOC was investigated by both whole cell patch clamp electrophysiology and a fluorescence based calcium assay. RESULTS: Transfection of 20 nM siRNA specific for STIM1 or 2 resulted in robust decreases (>70%) of the relevant mRNA. siRNA targeted at STIM1 resulted in a reduction of SOC associated Ca2+ influx in response to store depletion by cyclopiazonic acid (60%) or histamine but not bradykinin. siRNA to STIM2 had no effect on these responses. In addition STIM1 suppression resulted in a more or less complete abrogation of SOC associated inward currents assessed by whole cell patch clamp. CONCLUSION: Here we show that STIM1 acts as a key signal for SOC activation following intracellular Ca2+ store depletion or following agonist stimulation with histamine in human airway myocytes. These are the first data demonstrating a role for STIM1 in a physiologically relevant, non-transformed endogenous expression cell model.

Bronchi↗
PubMed2006

[Comparison between CT-discography and magnetic resonance imaging in lumbar disc diseases].

OBJECTIVE: To investigate the clinical importance of discography and CT after discography (CTD) in the lumbar disc diseases, and make a comparison between CTD and magnetic resonance imaging (MRI). METHODS: 265 patients with back and leg pain 177 males and 79 females, age 39 +/- 16, underwent discography and CT 2 hours later on 298 discs. All the patients' discs were classified into 7 types according to the findings by discography and CTD. Comprehensive MRI pictures were available in 237 of the 265 patients (with 257 discs); they accepted the MRI classification and were compared with the CT-discographic findings. RESULTS: 245 patients underwent operation, among which 247 discs showed visual lesions during the procedure and 238 cases (96.4%) had their disc diseases diagnosed accurately through discography and CTD. Considering the positive screening rate for the discogenic abnormality, the difference was of statistical significance between the CTD and MRI groups (P < 0.01). MRI was considered to have limited value in the disc diseases with passive discographic finding. CONCLUSION: Discography is an efficient, sound and safe assistant diagnostic tool, which can get some special information about disc. The matched-group study shows that the MRI and CTD can not be re placed by each other. MRI may act as the screening tool for disc diseases, but is inferior to CTD, especially for the contiguous disc structure in the spinal fixation procedure.

Adult↗
PubMed2006

Cloning, expression and characterization of a thermostable exo-beta-D-glucosaminidase from the hyperthermophilic archaeon Pyrococcus horikoshii.

An exo-beta-D-glucosaminidase gene (PH0511) was cloned from the hyperthermophilic archaeon, Pyrococcus horikoshii, and expressed in Escherichia coli. The purified protein showed a strong exo-beta-D: -glucosaminidase activity by TLC analysis. DTT (50 mM) had little effect on its homodimeric structure during SDS-PAGE. The enzyme was optimally active at 90 degrees C (over 20 min) and pH 6. It had a half-life of 9 h at 90 degrees C and is the most thermostable glucosaminidase described up to now. The activity was not inhibited by ethanol, 2-propanol, DMSO, PEG-400, denaturing agents SDS (5%, w/v), urea, guanidine hydrochloride (5 M) and Mg(2+), Mn(2+), Co(2+), Ca(2+), Sr(2+), Ni(2+) (at up to 10 mM).

Cations, Divalent↗
PubMed2006

Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists.

The discovery and pharmacological evaluation of potent, selective, and orally bioavailable growth hormone secretagogue receptor (GHS-R) antagonists are reported. Previously, 2,4-diaminopyrimidine-based GHS-R antagonists reported from our laboratories have been shown to be dihydrofolate reductase (DHFR) inhibitors. By comparing the X-ray crystal structure of DHFR docked with our GHS-R antagonists and GHS-R modeling, we designed and synthesized a series of potent and DHFR selective GHS-R antagonists with good pharmacokinetic (PK) profiles. An amide derivative 13d (Ca2+ flux IC50 = 188 nM, [brain]/[plasma] = 0.97 @ 8 h in rat) showed a 10% decrease in 24 h food intake in rats, and over 5% body weight reduction after 14-day oral treatment in diet-induced obese (DIO) mice. In comparison, a urea derivative 14c (Ca2+ flux IC50 = 7 nM, [brain]/[plasma] = 0.0 in DIO) failed to show significant effect on food intake in the acute feeding DIO model. These observations demonstrated for the first time that peripheral GHS-R blockage with small molecule GHS-R antagonists might not be sufficient for suppressing appetite and inducing body weight reduction.

Administration, Oral↗
PubMed2006

Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.

C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of inhibiting these enzymes and as leads for potential drugs targeting JNKs. In this report, we disclose a series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles.

Administration, Oral↗
PubMed2006

Ultrasonic-assisted size-controllable synthesis of Bi2Te3 nanoflakes with electrogenerated chemiluminescence.

Bi(2)Te(3) hexagonal nanoflakes with controllable edge length ranging from approximately 150 nm to as small as approximately 10nm were synthesized via an ultrasonic-assisted disproportionation route, using Te powder and Bi(NO(3))(3).5H(2)O as raw materials. The mechanochemical effects of the ultrasonic irradiation accelerated the reaction and were helpful to obtain relatively small and uniform nanocrystals. The products were characterized by X-ray powder diffraction, X-ray photoelectron spectra, transmission electron microscopy, and selected area electron diffraction techniques. Electrogenerated chemiluminescence of as-prepared Bi(2)Te(3) was also reported for the first time.

Journal Article↗
PubMed2006

Structural identification of methyl protodioscin metabolites in rats' urine and their antiproliferative activities against human tumor cell lines.

Methyl protodioscin (MPD), a furostanol saponin, is a preclinical drug shown potent antiproliferative activities against most cell lines from leukemia and solid tumors. The metabolites of MPD in rats' urine after single oral doses of 80 mg/kg were investigated in this research. Ten metabolites were isolated and purified by liquid-liquid extraction, open-column chromatography, medium-pressure liquid chromatography, and preparative high-performance liquid chromatography. The structural identification of the metabolites was carried out by high resolution mass spectra, NMR spectroscopic methods including (1)H NMR, (13)C NMR and 2D NMR, as well as chemical ways. The 10 metabolites were elucidated to be dioscin (M-1), pregna-5,16-dien-3beta-ol-20-one-O-alpha-l-rhamnopyranosyl-(1-->2)-[alpha-l-rhamnopyranosyl-(1-->4)]-beta-d-glucopyranoside (M-2), diosgenin (M-3), protobioside (M-4), methyl protobioside (M-5), 26-O-beta-d-glucopyrannosyl(25R)-furan-5-ene-3beta, 22alpha, 26-trihydroxy-3-O-alpha-l-rhamnopyranosyl-(1-->4)-beta-d-glucopyranoside(M-6),26-O-beta-d-glucopyranosyl(25R)-furan-5-ene-3beta,26-dihydroxy-22-methoxy-3-O-alpha-l-rhamnopyranosyl-(1-->4)-beta-d-glucopyranoside (M-7), prosapogenin A of dioscin (M-8), prosapogenin B of dioscin (M-9), and diosgenin-3-O-beta-d-glucopyranoside (M-10), respectively. M-1 was the main urinary metabolite of MPD in rats. Some metabolites showed potent antiproliferative activities against HepG2, NCI-H460, MCF-7 and HeLa cell lines in vitro.

Animals↗
PubMed2006

Platinum catalysts prepared with functional carbon nanotube defects and its improved catalytic performance for methanol oxidation.

Carbon nanotube (CNT) supported Pt nanoparticle catalysts have been prepared by spontaneous reduction of PtCl6(2-) ion as a result of direct redox reactions between PtCl6(2-) and oxygen-containing functional groups at defect sites of CNTs, which were introduced by chemical and electrochemical oxidation treatment of CNTs. The electrocatalytic properties of as-prepared Pt-CNT catalysts for methanol oxidation were investigated by chronopotentiometry and cyclic voltammetry. Compared with Pt catalysts prepared by hydrogen reduction and electrochemical deposition methods, Pt catalysts synthesized by functional CNT defects show excellent antipoisoning ability and long-term cycle stability.

Journal Article↗