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Biomedical subjects

Li Zhang

Publications and source records attributed to Li Zhang.

At least 181 records · Page 10Linked to original sources
PubMed2006

Atorvastatin downregulates tissue plasminogen activator-aggravated genes mediating coagulation and vascular permeability in single cerebral endothelial cells captured by laser microdissection.

The effects of statins on gene expression of cerebral endothelial cells (ECs) in vivo have not been investigated after stroke. We developed a rapid double immunofluorescent staining protocol with antibodies against von Willebrand factor (a marker for endothelium) and glial fibrillary acidic protein (a marker for astrocytes) for laser capture microdissection to isolate single ECs in brain tissue of the rat. Using this protocol in combination with real-time PCR, we found that stroke significantly increased mRNA levels of protease-activated receptor 1 (PAR-1) and tissue factor (TF) in ECs isolated from ischemic cerebral microvessels compared with nonischemic vessels. Treatment of embolic stroke with recombinant human tissue plasminogen activator (rht-PA) 4 h after stroke further elevated PAR-1 mRNA levels nearly 1000-fold in the core and 500-fold in the boundary above the nonstroke group 30 h after stroke, while TF mRNA levels were elevated approximately 10 fold above the nonstroke group. Furthermore, stroke significantly increased matrix metalloproteinase (MMP) 2 and 9 mRNA levels in the ischemic core and boundary regions 6 and 30 h after stroke. Treatment with rht-PA-upregulated MMP2 expression in the ischemic boundary and core. Atorvastatin completely blocked rht-PA upregulation of the above genes, when atorvastatin in combination with rht-PA was administered 4 h after stroke. Monotherapy of atorvastatin 4 h after stroke did not significantly reduce expression of genes examined in the present study. These data provide evidence that atorvastatin reduces exogenous tPA-aggravated cerebral endothelial genes that mediate thrombosis and blood-brain barrier permeability, which could contribute to the beneficial effects of statins on thrombolytic treatment of acute stroke.

Animals↗
PubMed2006

Biomarkers of response to preoperative chemoradiation in esophageal cancers.

To identify a panel of biomarkers that predicts response of esophageal cancers to preoperative chemoradiation, our group profiled the gene expression of pretreatment cancer biopsies from patients with esophageal cancer. Six (32%) of these patients had pathologic complete response. All cancers except one that achieved pathologic complete response (83%) clustered in one molecular type (type I), while cancers that achieved less than pathologic complete response with one exception clustered in another molecular type (type II). Activated NF-kappaB was significantly associated with aggressive pathology. These data indicate that expression analysis of a limited set of biomarkers selected from the list of genes that were differentially regulated between the two subtypes can increase predictive power, and suggest that esophageal cancer with activated NF-kappaB may result in poor treatment outcome.

Adenocarcinoma↗
PubMed2006

Intestinal absorption of Stemona alkaloids in a Caco-2 cell model.

The intestinal absorption of neotuberostemonine and neostenine, two major bioactive alkaloids of the commonly used antitussive traditional Chinese medicine Stemona tuberosa Lour, was investigated using a Caco-2 monolayer model. Both alkaloids exhibited a high absorptive permeability which was higher for neostenine [P(app(AB)) = 12.03 +/- 1.14 x 10 (-6) cm/s] than for neotuberostemonine [P(app(AB)) = 9.27 +/- 0.79 x 10 (-6) cm/s], indicating that they are likely to be well absorbed and orally active. Furthermore, both alkaloids were identified to be the substrates of P-glycoprotein and have a transport preference from the basolateral to apical direction with efflux ratios between 2 and 3. Cyclosporin A dose-dependently inhibited the secretory permeability of these alkaloids and abolished their active efflux transport.

Alkaloids↗
PubMed2006

Induction of apoptosis by d-limonene is mediated by a caspase-dependent mitochondrial death pathway in human leukemia cells.

Using K562 and HL60 cell lines, we have investigated the anti-tumoral activity of d-limonene, a monocyclic monoterpene, in human leukemia cells. Apoptosis was evaluated by Hoechst staining and by the annexin V/propidium iodide binding assay. d-Limonene induced apoptosis in a dose- and time-dependent manner in both cell lines. Our findings and data, demonstrating an increase in Bax protein expression, the release of cytochrome c from mitochondria, and an increase in caspase-9 and cleaved caspase-3, but not caspase-8, after the treatment of d-limonene, all suggest that the mitochondrial death pathway is primarily involved in the development of d-limonene-induced apoptosis.

Anticarcinogenic Agents↗
PubMed2006

4-Hydroxy-2-nonenal upregulates endogenous antioxidants and phase 2 enzymes in rat H9c2 myocardiac cells: protection against overt oxidative and electrophilic injury.

This study was undertaken to determine if 4-hydroxy-2-nonenal (HNE) could upregulate antioxidants and phase 2 enzymes in rat H9c2 myocardiac cells, and if the upregulated defenses led to cytoprotection against oxidative and electrophilic injury. Incubation of H9c2 cells with HNE at noncytotoxic concentrations resulted in significant induction of cellular catalase, glutathione (GSH), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1), as determined by enzyme activity and/or protein expression. HNE treatment caused increased mRNA expression of catalase, gamma-glutamylcysteine ligase, GST-A1, and NQO1. Pretreatment of H9c2 cells with HNE led to significant protection against cytotoxicity induced by reactive oxygen and nitrogen species. HNE-pretreated cells also exhibited increased resistance to injury elicited by subsequent cytotoxic concentrations of HNE. Taken together, this study demonstrates that several antioxidants and phase 2 enzymes in H9c2 cells are upregulated by HNE and that the increased defenses afford protection against overt oxidative and electrophilic cardiac cell injury.

Aldehydes↗
PubMed2006

Syphilis among female sex workers in southwestern China: potential for HIV transmission.

OBJECTIVE: The objective of this study was to investigate the prevalence and risk factors of syphilis infection among female sex workers in a southwestern Chinese city along a drug trafficking route. METHODS: From December 2004 to January 2005, 343 female sex workers (FSWs) were recruited through community outreach and peer referring. Confidential questionnaire interviews were administered to collect information on sexual and other sexually transmitted diseases/HIV risk behaviors. Cervical and blood samples were collected to test for syphilis and HIV antibodies and Neisseria gonorrhoeae infection; Condyloma acuminatum infection was diagnosed clinically. RESULTS: Of 343 FSWs, 15.7% were infected with syphilis. The prevalence of HIV, gonorrhea, and C. acuminatum was 0.6%, 2.0%, and 1.5%, respectively. The subtype of 2 HIV-1 infections was both CRF 07BC. Nearly 10% of FSWs reported using illicit drugs. Consistent use, inconsistent use, and never use of condoms with commercial sex clients in the last month were reported by 53.9%, 38.5%, and 7.6% FSWs, respectively. Longer duration of sex work (odds ratio [OR] = 1.98; 95% confidence interval [CI] = 1.08-3.62), working at low-end establishments (OR = 2.03; 95% CI = 1.10-3.76), and if primary sex partners had sex with other women in the past 6 months (OR = 2.06; 95% CI = 1.08-3.91) were independently associated with syphilis infection. CONCLUSIONS: High prevalence of syphilis and overlapped unprotected commercial sex and drug using behaviors among FSWs along a drug-trafficking route may suggest a potential for rapid spread of HIV from injection drug users to FSWs and then to the general population and underscore the urgency of preventive interventions to break the bridge of FSWs for HIV/sexually transmitted disease spread.

Adolescent↗
PubMed2006

Atlas-driven lung lobe segmentation in volumetric X-ray CT images.

High-resolution X-ray computed tomography (CT) imaging is routinely used for clinical pulmonary applications. Since lung function varies regionally and because pulmonary disease is usually not uniformly distributed in the lungs, it is useful to study the lungs on a lobe-by-lobe basis. Thus, it is important to segment not only the lungs, but the lobar fissures as well. In this paper, we demonstrate the use of an anatomic pulmonary atlas, encoded with a priori information on the pulmonary anatomy, to automatically segment the oblique lobar fissures. Sixteen volumetric CT scans from 16 subjects are used to construct the pulmonary atlas. A ridgeness measure is applied to the original CT images to enhance the fissure contrast. Fissure detection is accomplished in two stages: an initial fissure search and a final fissure search. A fuzzy reasoning system is used in the fissure search to analyze information from three sources: the image intensity, an anatomic smoothness constraint, and the atlas-based search initialization. Our method has been tested on 22 volumetric thin-slice CT scans from 12 subjects, and the results are compared to manual tracings. Averaged across all 22 data sets, the RMS error between the automatically segmented and manually segmented fissures is 1.96 +/- 0.71 mm and the mean of the similarity indices between the manually defined and computer-defined lobe regions is 0.988. The results indicate a strong agreement between the automatic and manual lobe segmentations.

Algorithms↗
PubMed2006

Restoring warped document images through 3D shape modeling.

Scanning a document page from a thick bound volume often results in two kinds of distortions in the scanned image, i.e., shade along the "spine" of the book and warping in the shade area. In this paper, we propose an efficient restoration method based on the discovery of the 3D shape of a book surface from the shading information in a scanned document image. From a technical point of view, this shape from shading (SFS) problem in real-world environments is characterized by 1) a proximal and moving light source, 2) Lambertian reflection, 3) nonuniform albedo distribution, and 4) document skew. Taking all these factors into account, we first build practical models (consisting of a 3D geometric model and a 3D optical model) for the practical scanning conditions to reconstruct the 3D shape of the book surface. We next restore the scanned document image using this shape based on deshading and dewarping models. Finally, we evaluate the restoration results by comparing our estimated surface shape with the real shape as well as the OCR performance on original and restored document images. The results show that the geometric and photometric distortions are mostly removed and the OCR results are improved markedly.

Algorithms↗
PubMed2006

Effects of ethanol on adenosine 5'-triphosphate-gated purinergic and 5-hydroxytryptamine receptors.

This report of the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism highlights the actions of ethanol on purinergic (P2XRs) and 5-hydroxytryptamine3 (5-HT3Rs) receptors. Both P2XRs and 5-HT3Rs, are modulated by pharmacologically relevant concentrations of ethanol, with inhibition or stimulation of P2XR subtypes and stimulation of 5-HT3Rs, respectively. With regard to ethanol-modulatory actions, these 2 distinctly different receptor classes have been studied to a much lesser extent than other LGICs. The organizers and chairs were Daryl L. Davies and Tina K. Machu. John J. Woodward discusses the molecular pharmacology and physiology of P2XRs and 5-HT3Rs and sets the stage for a detailed investigation into the ethanol sensitivity of these channels by the invited speakers. Daryl L. Davies discusses the results from recent electrophysiological studies conducted in his and Dr. Woodward's laboratories, highlighting the actions of ethanol on P2XR subtypes. Jiang-Hong Ye discusses results from recent studies using loose-patch and whole-cell recordings on purinergic receptors expressed on neurons from the ventral tegmental area (VTA) in rats. Tina K. Machu discusses electrophysiological studies conducted in her and Dr. David Lovinger's laboratories on nonpore lining residues of the second transmembrane domain (TM2) of the 5-HT3A receptor. Li Zhang presents data demonstrating that F-actin cytoskeletons play a critical role in 5-HT3 receptor clustering in hippocampal neurons. Collectively, the presentations provided strong evidence that P2X and 5-HT3 receptors are important targets for ethanol action.

Animals↗
PubMed2006

Six specific lysine residues are crucial in maintaining the structure and function of soluble manganese stabilizing protein.

When manganese stabilizing protein (MSP) was treated with 0.5 mM N-succinimidyl propionate (NSP), the rebinding ability and oxygen-releasing capabilities of the modified MSP were not altered, in spite of changes of MSP surface Lys residues. Furthermore, far-ultraviolet circular dichroism and intrinsic fluorescence spectra analysis revealed that 0.5 mM NSP-modified MSP retained most of its native secondary and tertiary structure. Mapping of the sites of NSP modification by Staphylococcus V(8) protease digestion of the modified protein, as well as analysis by matrix-assisted laser desorption ionization-time of flight mass spectrometry, indicated that seven Lys residues were modified. The results suggested that these residues are not absolutely essential to the structure and function of MSP. However, when the NSP concentration was increased to 4 mM, the modified MSP was unable to bind photosystem II and completely lost its reactivating capability. Both far-ultraviolet circular dichroism and intrinsic fluorescence spectra analysis revealed a clear conformational change in MSP after 4 mM NSP treatment, suggesting that some Lys residues are involved in maintaining the structure and function of MSP. Analysis by matrix-assisted laser desorption ionization-time of flight mass spectrometry indicated that another six Lys residues, namely Lys20, Lys101, Lys196, Lys207, Lys130 (or Lys137) and Lys66 (or Lys76), were modified by 4 mM NSP. Therefore, these six Lys residues are crucial in maintaining the structure and function of soluble MSP.

Binding Sites↗
PubMed2006

Nongastric Helicobacter species detected in the intestinal tract of children.

The presence of members of the family Helicobacteraceae in the colon of children was investigated using PCR, denaturing gradient gel electrophoresis, and fluorescent in situ hybridization. The rate of detection of species belonging to the Helicobacteraceae family in children with inflammatory bowel disease (92%) and irritable bowel syndrome (100%) was found to be significantly higher than that in healthy children (25%) (P < 0.05).

Adolescent↗
PubMed2006

B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells.

The antiapoptotic protein Bcl-2 is overexpressed in a majority of breast cancers, and is associated with a diminished apoptotic response and resistance to various antitumor agents. Bcl-2 inhibition is currently being explored as a possible strategy for sensitizing breast cancer cells to standard chemotherapeutic agents. Antisense Bcl-2 oligonucleotides represent one method for blocking the antiapoptotic effects of Bcl-2. In this study, we show that antisense Bcl-2 efficiently blocks Bcl-2 expression, resulting in the apoptosis of breast cancer cells. Antisense Bcl-2-mediated cytotoxicity was associated with the induction of the B cell translocation gene 1 (BTG1). Importantly, knockdown of BTG1 reduced antisense Bcl-2-mediated cytotoxicity in breast cancer cells. Furthermore, BTG1 expression seems to be negatively regulated by Bcl-2, and exogenous expression of BTG1 induced apoptosis. These results suggest that BTG1 is a Bcl-2-regulated mediator of apoptosis in breast cancer cells, and that its induction contributes to antisense Bcl-2-mediated cytotoxic effects.

Apoptosis↗
PubMed2006

Antioxidants and phase 2 enzymes in cardiomyocytes: Chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury.

The increasing recognition of the role for oxidative stress in cardiac disorders has led to extensive investigation on the protection by exogenous antioxidants against oxidative cardiac injury. On the other hand, another strategy for protecting against oxidative cardiac injury may be through upregulation of the endogenous antioxidants and phase 2 enzymes in the myocardium by chemical inducers. However, our current understanding of the chemical inducibility of cardiac cellular antioxidants and phase 2 enzymes is very limited. In this study, using rat cardiac H9c2 cells we have characterized the concentration- and time-dependent induction of cellular antioxidants and phase 2 enzymes by 3H-1,2-dithiole-3-thione (D3T), and the resultant chemoprotective effects on oxidative cardiac cell injury. Incubation of H9c2 cells with D3T resulted in a marked concentration- and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). D3T treatment of H9c2 cells also caused an increase in mRNA expression of catalase, gamma-glutamylcysteine ligase catalytic subunit, GR, GSTA1, M1 and P1, and NQO1. Moreover, both mRNA and protein expression of Nrf2 were induced in D3T-treated cells. D3T pretreatment led to a marked protection against H9c2 cell injury elicited by various oxidants and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the oxidants as well as simulated ischemia-reperfusion. This study demonstrates that a series of endogenous antioxidants and phase 2 enzymes in H9c2 cells can be induced by D3T in a concentration- and time-dependent fashion, and that the D3T-upregulated cellular defenses are accompanied by a markedly increased resistance to oxidative cardiac cell injury.

Animals↗
PubMed2006

Effect of the co-occurring components from green tea on the intestinal absorption and disposition of green tea polyphenols in Caco-2 monolayer model.

This study aimed to investigate the effect of co-occurring components from green tea on the intestinal absorption and disposition of green tea polyphenols (GTPs) using the Caco-2 cell monolayer model. The absorption and secretion transport of the four GTPs, in the form of individual pure compounds, pure compound mixtures and green tea extract, were studied in the Caco-2 cell model. Four GTPs and their metabolites were analysed by HPLC/MS and HPLC coupled with electrochemical detector. The apparent permeability coefficients (P(app)) of each compound, as well as the metabolites (mainly sulfation and methylation conjugates) generated, were compared for the different dosing formulations utilized. The results showed that the absorption transport of the four GTPs in different dosing formulations was similar. However, the secretion transport profiles of (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) were altered when the GTP mixture was administered. It was suggested that transporter competition resulting in reduced efflux of EC, as well as metabolic competition resulting in reduced formation of EGC sulfate and methylated EGC sulfate, might be involved during the secretion transport of GTP mixture.

Biological Transport↗
PubMed2006

Role of four major components in the effect of Si-Ni-San, a traditional Chinese prescription, against contact sensitivity in mice.

Previously, we demonstrated the inhibitory effects of Si-Ni-San, a traditional Chinese prescription, on picryl chloride-induced ear contact sensitivity (PCl-CS). This study aimed to evaluate the role of the four major constituents contained in the prescription (saikosaponins, paeoniflorin, naringin and glycyrrhizin) in the inhibitory effect. When administered during the induction phase, saikosaponin a and glycyrrhizin showed significant inhibitory effects, while paeoniflorin and naringin did not. These components in Si-Ni-San also inhibited the activation and proliferation of T lymphocytes as well as the production of cytokines such as tumour necrosis factor-alpha and interferon-gamma to different extents. Saikosaponin a and paeoniflorin dose-dependently reduced the splenocyte adhesion to type I collagen, while glycyrrhizin only showed a slight tendency. Furthermore, treatment with glycyrrhizin or saikosaponin a, rather than paeoniflorin or naringin, moderately inhibited the matrix metalloproteinase (MMP)-2 activity of the splenocytes from PCl-CS mice, and the combination of all four components showed a strong inhibition against MMP-2. Moreover, the components markedly decreased the serum level of nitric oxide in PCl-sensitized mice. The results indicated that saikosaponin a and glycyrrhizin may be the major contributors in the alleviation effect of Si-Ni-San on contact sensitivity, and paeoniflorin and naringin may exhibit a co-operative effect.

Animals↗
PubMed2006

The roles of mucus-associated bacteria in inflammatory bowel disease.

The etiology of inflammatory bowel disease (IBD) is currently unknown. Although there is convincing evidence supporting a critical role for micro-organisms in the pathogenesis of IBD, the specific organisms involved remain undetermined. Mucus-associated bacteria have recently been considered as likely candidates for involvement in IBD; indeed several mucus-associated bacteria species have been shown to induce IBD-like conditions in animal models, and some of these bacteria have been detected in human intestinal tissues. Further studies are required to investigate the possible role of mucus-associated bacteria in human IBD.

Adult↗
PubMed2006

Double-negative regulatory T cells: non-conventional regulators.

The crucial role of regulatory T (Treg) cells in self-tolerance and downregulating immune responses has been clearly established. Numerous different Treg subsets have been identified that possess distinct phenotypes and functions in various disease models. Among these subsets, alphabeta-TCR+CD3+CD4-CD8- double-negative (DN) Treg cells have been shown to be able to inhibit a variety of immune responses in part via direct killing of effector T cells in an antigenspecific manner in both mice and humans. This was shown to occur at least partially by acquisition of MHC-peptide complexes from antigen-presenting cells (APCs) and subsequent Fas/Fas-ligand interactions. In addition, DN Treg cells have been shown to express several molecules uncommon to other Treg cell subsets, such as IFN-gamma, TNF-alpha, Ly6A, FcRgamma, and CXCR5, which may contribute to their unique regulatory ability. Understanding the development and regulatory functions of DN Treg cells may elucidate the etiology for loss of self-tolerance and serve as a therapeutic modality for various diseases. This review will summarize the characteristics, developmental pathways, and mechanisms of action of DN Treg cells, as well as their role in transplant tolerance, autoimmunity, and anticancer immunity.

Animals↗