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Lixin Zhang

Publications and source records attributed to Lixin Zhang.

At least 55 records · Page 3Linked to original sources
PubMed2004

Neurotrophic and neuroprotective effects of the neuregulin glial growth factor-2 on dopaminergic neurons in rat primary midbrain cultures.

Glial growth factor-2 (GGF2) and other neuregulin (NRG) isoforms have been shown to play important roles in survival, migration, and differentiation of certain neural and non-neural cells. Because midbrain dopamine (DA) cells express the NRG receptor, ErbB4, the present study examined the potential neurotrophic and/or neuroprotective effects of GGF2 on cultured primary dopaminergic neurons. Embryonic day 14 rat mesencephalic cell cultures were maintained in serum-free medium and treated with GGF2 or vehicle. The number of tyrosine hydroxylase-positive (TH+) neurons and high-affinity [3H]DA uptake were assessed at day in vitro (DIV) 9. Separate midbrain cultures were treated with 100 ng/mL GGF2 on DIV 0 and exposed to the catecholamine-specific neurotoxin 6-hydroxydopamine (6-OHDA) on DIV 4. GGF2 treatment significantly increased DA uptake, the number of TH+ neurons, and neurite outgrowth when compared to the controls in both the serum-free and the 6-OHDA-challenged cultures. Furthermore, three NRG receptors were detected in the midbrain cultures by western blot analysis. Immunostaining for glial fibrillary acidic protein revealed that GGF2 also weakly promoted mesencephalic glial proliferation in the midbrain cultures. These results indicate that GGF2 is neurotrophic and neuroprotective for developing dopaminergic neurons and suggest a role for NRGs in repair of the damaged nigrostriatal system that occurs in Parkinson's disease.

Animals↗
PubMed2004

Vaccination of rabbits with an adenovirus vector expressing the papillomavirus E2 protein leads to clearance of papillomas and infection.

Cervical cancer arises from lesions caused by infection with high-risk types of human papillomavirus (HPV). Therefore, vaccination against HPV could prevent carcinogenesis by preventing HPV infection or inducing lesion regression. HPV E2 protein is an attractive candidate for vaccine development because it is required for papilloma formation, is involved in all stages of the virus life cycle, and is expressed in all premalignant lesions as well as some cancers. This study reports vaccination against E2 protein using a rabbit model of papillomavirus infection. A recombinant adenovirus (Ad) vector expressing the E2 protein of cottontail rabbit papillomavirus (CRPV) was tested for therapeutic efficacy in CRPV-infected rabbits. Primary immunization with the Ad-E2 vaccine, compared to immunization with a control Ad vector, reduced the number of papilloma-forming sites from 17 of 45 to 4 of 45. After booster immunization, vaccinated rabbits formed no new papillomas versus an additional 23 papillomas in rabbits that received the control vector. Papillomas in the Ad-E2 vaccinees were significantly smaller than those in the control rabbits, and all four papillomas in the Ad-E2 vaccinated rabbits regressed. No CRPV DNA was detected either in the regression sites or in sites that did not form papillomas, indicating that the vaccination led to clearance of CRPV from all infected sites.

Adenoviridae↗
PubMed2004

Identification of potential modifiers of Runx2/Cbfa1 activity in C2C12 cells in response to bone morphogenetic protein-7.

Treatment with BMP-7 causes a shift in the differentiation pathway from myoblastic to osteoblastic in C2C12 mouse myoblast precursor cells in vitro. The underlying molecular mechanism is largely unknown. BMP-7 at 200 ng/ml completely inhibited myotube formation in C2C12 cells and dramatically induced alkaline phosphatase activity up to 20-fold when compared to untreated cells by day 12 in culture. The level of Runx2/Cbfa1 mRNA, a bone-specific transcription factor, was also stimulated up to 6-fold by BMP-7 with a peak at 24 h. In addition BMP-7 treatment stimulated a 55-fold increase in osteocalcin mRNA as early as 24 h after treatment. A novel finding was that the expression of the chondrocyte markers Sox9 and type II collagen was increased as well. Runx2/Cbfa1 is a molecular switch for osteoblast differentiation. To initiate the study of modulators of Runx2/Cbfa1, such as kinases and cofactors, during osteoblastic differentiation of C2C12 cells treated by BMP-7 in vitro, microarray analyses of gene expressions were performed. Microarray data suggested that a total of 882 transcripts were either up- or downregulated at least 2-fold. Cluster analyses revealed 76 genes (including ESTs) with expression patterns that paralleled Runx2/Cbfa1. Thirteen of these 76 genes were initially selected as potential transcription modulators for further study; including CCAAT/enhancer binding protein delta, distal- less homeobox 1, forkhead box F2, insulin-like growth factor binding protein 4, an ortholog of human osteoclast stimulating factor 1 and p300/CBP-associated factor. Some transcription modulators have been associated with osteoblastic differentiation or interacted with Runx2/Cbfa1. Most of them have not been extensively studied in osteoblastic differentiation and in relationship to Runx2/Cbfa1. Thus, these studies identify potential regulators for Runx2/Cbfa1 and osteoblast differentiation. In addition, our data revealed for the first time that BMP-7 not only induced the expression of osteoblastic differentiation markers but also stimulated the expression of chondroblastic markers in C2C12 cells.

Acetyltransferases↗
PubMed2004

STAT3-mediated signaling in the determination of rod photoreceptor cell fate in mouse retina.

PURPOSE: The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the development of rod photoreceptors in the mouse retina. METHODS: Retina explant cultures derived from timed-pregnant CD-1 mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted retinas were harvested at distinct time points and processed for immunohistochemistry. RESULTS: Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal development of rods in retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod development by CNTF. CONCLUSIONS: These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development.

Animals↗
PubMed2004

Affinity capillary electrophoresis analyses of protein-protein interactions in target-directed drug discovery.

Protein-protein interactions are instrumental in virtually all biological processes and their understanding will shed light on designing novel and effective drugs for therapeutic interventions targeting the pathways in which they function. Protein-protein interactions have been studied using many genetic and biochemical methods, most recently, affinity capillary electrophoresis (ACE). We used ACE as a high-throughput screening assay to establish and define binding interactions between a therapeutic target protein and chemical entities from natural product or synthetic chemical libraries. Furthermore, ACE has demonstrated its value in the measurement of binding constants, the estimation of kinetic rate constants, and the determination of the stoichiometry of protein-protein interactions. Herein, we will describe qualitatively several assay formats using ACE for detecting protein-protein interactions, and discuss their advantages and limitations.

Animals↗
PubMed2004

[Effect of insect pest on activated oxygen metabolism in lanceolate leaves of Populus euphratica under different water condition].

This paper studied the effect of insect pest on the activities of protective enzymes SOD and CAT and the contents of H2O2 and O2*- in lanceolate leaves of Populus euphratica under different soil water conditions. The results showed that soil water deficiency did not increase SOD and CAT activities and H2O2 and O2*- contents in lanceolate leaves, but under this condition, insect pest increased them. When soil water was abundance, insect pest couldn't increase the activities of SOD and CAT and the contents of H2O2 and O2*- in lanceolate leaves. It's concluded that insect pest had an important role in death of Populus euphratica under soil water deficiency.

Animals↗
PubMed2004

[Necrosed field model of high intensity focused ultrasound for tumor treatment].

High intensity focused ultrasound (HIFU) has become a new developed micro-invasive surgical treatment of tumor, which is a hot topic in basic and applied research field. HIFU has shown its unique advantages including micro-invasion and curative effect during the treatment of several kinds of superficial tumor, e. g. mammary cancer. Based on the cellular thermo-necrotic theory, the expression of omega value was introduced to establish the mathematic model of the necrosed field formed in HIFU treatment progress. A non-interferential and self-focused system with multi-transducer was used to verify the theoretical model. Results of this study proved that the necrosed field mathematic model can simulate the actual heating progress. The model of this study may predict the practical value of the necrosed field as well as the time needed to take shape.

Breast Neoplasms↗
PubMed2003

An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells.

To develop a method to overcome the anergy that exists in tumor hosts to cancer, we have designed an adenoviral vector for the in vivo activation and tumor antigen loading of dendritic cells. This adenoviral vector encodes a fusion protein composed of an amino-terminal tumor-associated antigen fragment fused to the CD40 ligand (CD40L). Subcutaneous injection of an adenoviral vector encoding a fusion protein of the human papillomavirus E7 foreign antigen linked to the CD40L generates CD8+ T cell-dependent immunoresistance to the growth of the E7-positive syngeneic TC-1 cancer cells in C57BL/6 mice for up to 1 year. We also studied the s.c. injection of a vector carrying the gene for the human MUC-1 (hMUC-1) self-antigen fused to the CD40L. When this vector was injected into hMUC-1.Tg mice, which are transgenic for the hMUC-1 antigen, the growth of syngeneic hMUC-1-positive LL1/LL2hMUC-1 mouse cancer cells was suppressed in 100% of the injected animals. The hMUC-1.Tg mice are anergic to the hMUC-1 antigen before the injection of the vector. These experimental results show that it is possible to use vector injection to activate a long-lasting cellular immune response against self-antigens in anergic animals. The vector-mediated in vivo activation, and tumor-associated antigen loading of dendritic cells does not require additional cytokine boosting to induce the immune response against the tumor cells. This vector strategy may therefore be of use in the development of immunotherapy for the many carcinomas in which the hMUC-1 antigen is overexpressed.

Adenoviridae↗
PubMed2003

Molecular epidemiology of Escherichia coli mediated urinary tract infections.

Urinary tract infection (UTI) is one of the most frequently acquired bacterial infections and Escherichia coli accounts for as many as 90% of all UTIs seen among ambulatory populations. Risk factors for UTIs include host behaviors, host characteristics and bacterial characteristics. Sexual activity and contraceptive method are the strongest determinant of a symptomatic UTI episode. The characteristics of cell receptors, anatomical differences and genetic predisposition in the host may be important determinants of increased risk for recurrent infections. Uropathogenic E. coli have special characteristics causing urovirulence. They most likely belong to phylogenic lineage B2. They usually possess specific adhesins such as P, S or Dr to facilitate their colonization in the urinary tract, and toxins such as hemolysin and cytotoxic necrotizing factor 1 to provoke inflammatory response that possibly are responsible for the development of UTI symptoms. Interestingly, virulence genes in uropathogenic E. coli are often co-located on pathogenicity islands. Currently, however, none of the known virulence genes or set of genes can clearly define the prototypic uropathogenic E. coli. Additional studies are needed to identify factors that promote uropathogen transmission and persistent colonization, and to investigate potential different modes of pathogenesis by E. coli strains with different compositions of virulence genes.

Animals↗
PubMed2003

Cytotoxic effect of replication-competent adenoviral vectors carrying L-plastin promoter regulated E1A and cytosine deaminase genes in cancers of the breast, ovary and colon.

Prodrug activating transcription unit gene therapy is one of several promising approaches to cancer gene therapy. Combining that approach with conditionally replication-competent viral vectors that are truly tumor specific has been an important objective of recent work. In this study, we report the construction of a new conditionally replication-competent bicistronic adenoviral vector in which the cytosine deaminase (CD) gene and the E1a gene are driven by the L-plastin tumor-specific promoter (AdLpCDIRESE1a). A similar vector driven by the CMV promoter has also been constructed (AdCMVCDIRESE1a) as a control. We have carried out in vitro cytotoxicity in carcinomas of the breast, ovary and colon, and in vivo efficacy studies with these vectors in an animal model of colon cancer. While the addition of the AdLpCDIRESE1a vector to established cancer cell lines showed significant cytotoxicity in tumor cells derived from carcinomas of the breast (MCF-7), colon (HTB-38) and ovary (Ovcar 5), no significant toxicity was seen in explant cultures of normal human mammary epithelial cells (HMEC) exposed to this vector. The addition of 5-fluorocytosine (5FC) significantly increased the cytotoxicity in an additive fashion of both the AdLpCDIRESE1a and AdCMVCDIRESE1a vectors as well as that of the AdLpCD replication incompetent vector to established tumor cell lines. However, no significant cytotoxicity was observed with the addition of 5FC to explant cultures of normal human mammary epithelial cells that had been exposed to the L-plastin-driven vectors. Studies with mixtures of infected and uninfected tumor cell lines showed that the established cancer cell lines infected with the AdLpCDIRESE1a vector generated significant toxicity to surrounding uninfected cells (the "bystander effect") even at a ratio of 0.25 of infected cells to infected + uninfected cells in the presence of 5FC. The injection of the AdLpCDIRESE1a vector into subcutaneous deposits of human tumor nodules in the nude mice was potentiated by administering 5-FC by intraperitoneal injection. This treatment resulted in a decreased tumor size and a decreased tumor cell growth rate. The mice treated with a combination of the AdLpCDIRESE1a vector intratumoral injection and intraperitoneal 5FC injections lived much longer than the other experimental groups exposed to the viral vector alone or to the combination of the intratumoral AdLpCD replication incompetent vector injections plus intraperitoneal 5-FC injections. These encouraging results with our newly constructed AdLpCDIRESE1a vector suggest a need for further study of its utility in a preclinical model of intracavitary therapy of pleural or peritoneal carcinomatosis.

Adenoviridae↗
PubMed2003

Changes in some enzymes of microbodies and plastid development in excised radish cotyledons: effect of narciclasine.

Narciclasine (NCS), isolated from mucilage of Narcissus bulb, showed inhibitory effects on growth and plastid development of excised radish cotyledons. NCS (0.1 mumol/L) started to show inhibitory effects on isocitrate lyase and hydroxypyruvate reductase activities after 24 h incubation in light. When NCS concentration was increased to 10 mumol/L, the activities of both enzymes are completely inhibited. From ultrastructural studies, NCS markedly prevented the degradation of protein bodies and lipid bodies, as well as chloroplast formation of excised radish cotyledons. There was only little degradation of protein and lipid bodies, and almost no chloroplast formation in the excised radish cotyledon treated with 1 mumol/L NCS. Therefore, our results provide clear evidence that NCS inhibited the transition of glyoxysomes and peroxisomes, and chloroplast development.

Alcohol Oxidoreductases↗
PubMed2003

Evaluation of genotyping large numbers of Escherichia coli isolates by enterobacterial repetitive intergenic consensus-PCR.

We analyzed a large collection of Escherichia coli isolates typed by enterobacterial repetitive intergenic consensus (ERIC)-PCR with BioNumerics gel analysis software. However, the interexperimental variation of ERIC-PCR caused the computer software to classify repeated isolates as different. ERIC-PCR should not be used as the sole determinant of genetic similarity when typing large numbers of bacterial isolates via computer software.

Base Sequence↗
PubMed2002

Uropathogenic Escherichia coli are more likely than commensal E. coli to be shared between heterosexual sex partners.

Because uropathogenic Escherichia coli are better adapted than other E. coli to the urethra, periurethra, and vagina, the authors reasoned that uropathogenic E. coli would be more likely than commensal E. coli to be shared between sex partners. In this 1996-1999 Michigan study, the genetic identity of E. coli isolated from 166 women with E. coli urinary tract infection (UTI) and 94 women without UTI and their sex partners was determined by pulsed-field gel electrophoresis. Rectal isolates were considered uropathogenic E. coli if genetically identical to the urinary isolate causing UTI. All eight urinary isolates from men with UTI partners were identical to the E. coli found in the urine or vagina of their sex partner. When the 550 unique rectal E. coli isolates from couples were considered the unit of analysis, E. coli that caused UTI were nine times (odds ratio (OR) = 8.87, 95% confidence interval (CI): 5.41, 14.54) more likely than other E. coli to be shared between sex partners. Sharing occurred twice as frequently (OR = 1.87, 95% CI: 1.13, 3.08) if the E. coli had P pili or if the couples engaged in oral sex (OR = 2.09, 95% CI: 1.09, 4.00). Uropathogenic E. coli are more likely than commensal E. coli to be shared with a current heterosexual sex partner. Both sexual behaviors and a bacterial virulence factor, P pili, modified sharing.

Adaptation, Physiological↗
PubMed2002

Molecular epidemiology of 3 putative virulence genes for Escherichia coli urinary tract infection-usp, iha, and iroN(E. coli).

This study describes the epidemiological association of 3 putative genes for virulence of uropathogenic Escherichia coli; uropathogenic specific protein (usp), a Vibrio cholerae zot gene homologue; IrgA homologue adhesin (iha), a nonhemagglutinating adhesin; and iroN(E. coli), a catechole siderophore receptor homologue. We compared the relative frequency in urinary tract infection (UTI) isolates (n=508), compared with non-UTI isolates (n=416). iroN(E. coli) occurred 2.1-3.6 times more frequently in UTI isolates than in rectal isolates (P=1.1x10-18 to P=2.7x10-5) and was associated with several uropathogenic virulence genes found on pathogenicity islands. usp occurred more frequently in isolates from patients with pyelonephritis (P=3.6x10-9), in periurethral isolates (P=.001), and in isolates from patients with UTI who were aged 40-65 years (P=.004), when compared with the rectal isolates; iha was not associated with UTI in this study.

Adolescent↗
PubMed2002

Synthesis, membrane insertion and assembly of the chloroplast-encoded D1 protein into photosystem II.

Rapid light-dependent turnover of the chloroplast-encoded D1 protein maintains photosystem II (PS II) functional over a wide range of light intensities. Following initiation of psbA mRNA translation, the elongating D1 is targeted, possibly by chloroplast signal recognition particle 54 (cpSRP54), to the thylakoid cpSecY translocation channel. Transmembrane domains of nascent D1 start interacting with other PS II core proteins already during the translocation process to ensure an efficient assembly of the multiprotein membrane complex. Here we review the progress recently made concerning the synthesis, targeting, membrane insertion and assembly to PS II of the chloroplast-encoded D1 protein and discuss the possible convergence of targeting and translocation of chloroplast- and nuclear-encoded thylakoid proteins.

Chloroplasts↗
PubMed2002

Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively cytolytic for breast cancer and melanoma.

We have previously demonstrated that a truncated form of the L-plastin promoter can confer tumor-specific patterns of expression on replication-incompetent adenoviral vector reporter and therapeutic transcription units. In this report, a 2.5-kb truncated version of the L-plastin promoter was placed 5' to the E1A gene of a wild-type adenovirus. The vector generated (Ad-Lp-E1A) was directly cytotoxic to established breast and ovarian cancer cell lines and to primary explant cultures derived from ovarian cancer, but was not cytotoxic to explant cultures of normal mammary epithelial cells. This vector was not cytotoxic to cell lines in which the L-plastin E1A transcription unit was not expressed, whereas the same cell lines were sensitive to the cytotoxic effect of a replication-competent adenoviral vector in which the cytomegalovirus (CMV) promoter drove E1A expression. When the tyrosinase promoter/enhancer was placed 5' to the E1A gene in the adenoviral backbone, the resulting vector (Ad-Tyr-E1A) was selectively toxic to melanoma cells and one percent as toxic to explants of ovarian cancer cells as the Ad-Lp-E1A vector. Injection of these vectors (Ad-Lp-E1A and Ad-Tyr-E1A) into nodules derived from the MCF-7 and MDA-MB-468 human breast cancer cell lines and the TF-2 human melanoma cell line, respectively, which were growing subcutaneously in severe combined immunodeficiency (SCID) mice, induced regression of these tumors. Such vectors may therefore be useful in cancer treatment.

Adenoviridae↗
PubMed2002

Variations in 10 putative uropathogen virulence genes among urinary, faecal and peri-urethral Escherichia coli.

A total of 868 isolates was screened from seven different collections of organisms from previous studies - pyelonephritis in children aged 1-24 months; first, second and recurring urinary tract infection (UTI) in women aged 18-39 years; UTI in women aged 40-65 years and peri-urethral and faecal isolates from women aged 18-39 years - for the presence of 10 potential Escherichia coli UTI virulence genes. Previously reported differences between the frequency of these genes in UTI compared with faecal isolates were confirmed and extended. A single virulence signature (strains containing aer, kpsMT, ompT, fim and papGAD) occurred in 29% of the pyelonephritic isolates, but in no more than 11% of the other collections. Peri-urethral isolates were found to have frequencies of these 10 genes that differed from those found for both UTI and faecal isolates.

Adolescent↗