Biomedical subjects

Xiaomei Wang

Publications and source records attributed to Xiaomei Wang.

At least 19 recordsLinked to original sources

PubMed2007

Proliferative status of tumor stem cells may be correlated with malignancy grade of human astrocytomas.

Tumor stem cells are implicated in tumor initiation and maintenance. Recent studies have shown that a subpopulation of cells isolated from brain tumors can form neurospheres in vitro, and have multiple characteristic properties observed in neural stem cells. In vivo implantation of these cells can induce tumors that phenocopy original tumors, suggesting that tumor stem cells are involved in brain carcinogenesis. We found that a population of cells in human glioblastoma multiforme expressed multiple protein markers of neural stem cells including nestin, TUC-4, doublecortin and beta III-tubulin. In contrast, these markers were not expressed in human capillary hemangioblastoma or meningioma. Double immunolabeling showed that a portion of doublecortin-, beta III-tubulin-, TUC-4- and nestin-positive cells express Ki67 antigen, a cell proliferation marker. To investigate further whether these properties of tumor stem cells are correlated with their biological behavior, immunohistochemistry was performed on brain sections from astrocytomas of different grades using antibodies against neural stem cell markers. The number of cells expressing Ki67 antigen and neural stem cell markers was increased in relation to worsening histological grade of astrocytomas, indicating that the capacity for tumor stem cell proliferation may be clinically relevant. Thus, tumor stem cells in astrocytomas may be involved in carcinogenesis.

Adolescent↗

PubMed2006

Recruitment of macrophages and polymorphonuclear leukocytes in Lyme carditis.

Lyme arthritis, caused by the spirochete Borrelia burgdorferi, can be recurrent or prolonged, whereas Lyme carditis is mostly nonrecurring. A prominent difference between arthritis and carditis is the differential representation of phagocytes in these lesions: polymorphonuclear leukocytes (PMN) are more prevalent in the joint, and macrophages predominate in the heart lesion. We have previously shown differential efficiency of B. burgdorferi clearance by PMN and macrophages, and we now investigate whether these functional differences at the cellular level may contribute to the observed differences in organ-specific pathogenesis. When we infected mice lacking the neutrophil chemokine receptor (CXCR2(-/-) mice) with spirochetes, we detected fewer PMN in joints and less-severe arthritis. Here we have investigated the effects of the absence of the macrophage chemokine receptor CCR2 on the development and resolution of Lyme carditis in resistant (C57BL/6J [B6]) and sensitive (C3H/HeJ [C3H]) strains of mice. In B6 CCR2(-/-) mice, although inflammation in hearts is mild, we detected an increased burden of B. burgdorferi compared to that in wild-type (WT) mice, suggesting reduced clearance in the absence of macrophages. In contrast, C3H CCR2(-/-) mice have severe inflammation but a decreased B. burgdorferi burden compared to that in WT C3H mice both at peak disease and during resolution. Histopathologic examination of infected hearts revealed that infected C3H CCR2(-/-) animals have an increased presence of PMN, suggesting compensatory mechanisms of B. burgdorferi clearance in the hearts of infected C3H CCR2(-/-) mice. The more efficient clearance of B. burgdorferi from hearts by CCR2(-/-) versus WT C3H mice suggests a natural defect in the recruitment or function of macrophages in C3H mice, which may contribute to the sensitivity of this strain to B. burgdorferi infection.

Animals↗

PubMed2006

Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts.

Carbon monoxide (CO), a byproduct of heme catabolism by heme oxygenase (HO), confers potent antiinflammatory effects. Here we demonstrate that CO derived from HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3-dependent signaling, in macrophages. Ligand-mediated receptor trafficking to lipid rafts represents an early event in signal initiation of immune cells. Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase, and in gp91(phox)-deficient macrophages. CO selectively inhibited ligand-induced recruitment of TLR4 to lipid rafts, which was also associated with the inhibition of ligand-induced ROS production in macrophages. TLR3 did not translocate to lipid rafts by polyinosine-polycytidylic acid (poly(I:C)). CO had no effect on poly(I:C)-induced ROS production and TLR3 signaling. The inhibitory effect of CO on TLR-induced cytokine production was abolished in gp91(phox)-deficient macrophages, also indicating a role for NADPH oxidase. CO attenuated LPS-induced NADPH oxidase activity in vitro, potentially by binding to gp91(phox). Thus, CO negatively controlled TLR signaling pathways by inhibiting translocation of TLR to lipid rafts through suppression of NADPH oxidase-dependent ROS generation.

Animals↗

PubMed2006

Evidence for stroke-induced neurogenesis in the human brain.

Experimental stroke in rodents stimulates neurogenesis and migration of newborn neurons from their sites of origin into ischemic brain regions. We report that in patients with stroke, cells that express markers associated with newborn neurons are present in the ischemic penumbra surrounding cerebral cortical infarcts, where these cells are preferentially localized in the vicinity of blood vessels. These findings suggest that stroke-induced compensatory neurogenesis may occur in the human brain, where it could contribute to postischemic recovery and represent a target for stroke therapy.

Adult↗

PubMed2006

Changes in VP3 and VP5 genes during the attenuation of the very virulent infectious bursal disease virus strain Gx isolated in China.

A very virulent infectious bursal disease virus (vvIBDV) Gx strain with high pathogenicity was attenuated through replication in specific-pathogen free (SPF) chicken embryos and in chicken embryo fibroblast (CEF) cell cultures. The changes in nucleotide sequences and the deduced amino acid sequences of VP3 and VP5 genes during attenuation were obtained. Sequence analysis of selected passages from numbers 0 to 20 in CEF's (designated here Gx to CEF-20) showed that there were no amino acid changes detected in the VP3 and VP5 genes before CEF-9. There were some changes in the nucleotide sequence and amino acid substitutions in the VP3 and VP5 genes at CEF-9. CEF-9 was an intermediate with some amino acid changes which were possibly related to virulence. The amino acid sequences of VP2 and VP5 genes remained unchanged from CEF-10 to CEF-20. The results of pathogenicity test showed that the mortalities of vvIBDV-Gx, CEF-5, CEF-8, and CEF-9 were 64, 60, 60, and 28%, respectively, while there were no mortalities observed for CEF-10, CEF-15 and CEF-20. There was also no bursal atrophy when chickens were inoculated with CEF-10, CEF-15, and CEF-20. Virus neutralization tests with the Gx strain and sera from inoculated chickens showed that the antigenicity was similar from Gx to CEF-20. The implications of these findings for the study of IBDV virulence and a more effective control of vvIBDV are discussed.

Amino Acid Sequence↗

PubMed2006

ZnO-based hollow microspheres: biopolymer-assisted assemblies from ZnO nanorods.

Many efforts have been made in fabricating three-dimensional (3D) ordered zinc oxide (ZnO) nanostructures due to their growing applications in separations, sensors, catalysis, bioscience, and photonics. Here, we developed a new synthetic route to 3D ZnO-based hollow microspheres by a facile solution-based method through a water-soluble biopolymer (sodium alginate) assisted assembly from ZnO nanorods. The products were characterized by X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, selected area electron diffraction, and X-ray photoelectron spectroscopy. Raman and photoluminescence spectra of the ZnO-based hollow microspheres were obtained at room temperature to investigate their optical properties. The hollow microspheres exhibit exciting emission features with a wide band covering nearly all the visible region. The calculated CIE (Commission Internationale d'Eclairage) coordinates are 0.24 and 0.31, which fall at the edge of the white region (the 1931 CIE diagram). A possible growth mechanism of the 3D ZnO superstructures based on typical biopolymer-crystal interactions in aqueous solution is tentatively proposed, which might be really interesting because of the participation of the biopolymer. The results show that this biopolymer-directed crystal growth and mediated self-assembly of nanocrystals may provide promising routes to rational synthesis of various ordered inorganic and inorganic-organic hybrid materials with complex form and structural specialization.

Biopolymers↗

PubMed2006

Diversity, structure, and expression of the gene for p26, a small heat shock protein from Artemia.

p26, a small heat shock protein, is thought to protect Artemia embryos from stress during encystment and diapause. Full-length p26 cDNAs were compared and used to determine phylogenetic relationships between several Artemia species. The alpha-crystallin domain of p26 was the most conserved region of the protein and p26 from each Artemia species contained characteristic amino-terminal WD/EPF and carboxy-terminal VPI motifs. Sequence conservation suggested the importance of p26 to oviparously developing Artemia embryos and indicated common functions for the protein during development and stress resistance, although as shown by modeling some species-specific p26 amino acid substitutions may have adaptive significance. The p26 gene obtained from A. franciscana exhibited a unique sHSP intron arrangement with an intron in the 5'-untranslated region. Computer-assisted analysis revealed heat shock elements and other putative cis regulatory sequences but their role in gene regulation is unknown. In contrast to previous results for which Northern blots were analyzed, p26 gene expression was observed in ovoviviparous embryos by use of PCR-based methodology, but the p26 protein was not detected.

Amino Acid Sequence↗

PubMed2006

Evaluation of brain-targeting for the nasal delivery of estradiol by the microdialysis method.

The uptake of estradiol into the cerebrospinal fluid (CSF) after intranasal and intravenous administration in rats was investigated to study whether direct nose-CSF transport of estradiol exits or not. Animals received 0.48 mg kg(-1) estradiol randomly methylated beta-cyclodextrin (RAMEB) inclusion complex intranasally and intravenously. Following nasal delivery, estradiol reached a C(max) value (mean+/-S.D.) in plasma (26.70+/-11.37 ng ml(-1)) and CSF (54.76+/-32.84 ng ml(-1)) after 20 min in each case, while after intravenous infusion, estradiol reached a C(max) value in plasma (170.08+/-64.67 ng ml(-1)) and CSF (26.48+/-11.34 ng ml(-1)) at 5 min and 60 min, respectively. The AUC(CSF)/AUC(plasma) ratio (1.60+/-0.67) after intranasal delivery differed significantly from the ratio (0.61+/-0.16) observed after intravenous infusion (P<0.05). All these results indicate that estradiol is transported into CSF via olfactory neurons, and, hence, there is a direct transport route from the nasal cavity into the CSF for estradiol.

Administration, Intranasal↗

PubMed2006

Serotonin depletion attenuates AY-9944-mediated atypical absence seizures.

PURPOSE: To test the hypothesis that serotonin (5-HT) plays a role in the modulation of experimental atypical absence seizures. METHODS: Male Long-Evans hooded rats were treated from postnatal day (P) 2 to P20 with the cholesterol inhibitor AY-9944 (AY). Epidural electrodes were implanted for electrocorticography (ECoG) followed by serotonin depletion by using para-cholorophenylalanine (PCPA). High-performance liquid chromatography (HPLC) was used to measure the levels of serotonin and its metabolite (5-HIAA) in various brain regions. Serotonin metabolism was computed by using the 5-HIAA/5-HT ratio and used to ascertain differences between groups. RESULTS: PCPA treatment was associated with a significant decrease in the total slow spike-and-wave discharge (SSWD) duration in AY-treated rats compared with controls (p < 0.01). HPLC data confirmed the PCPA depletion of 5-HT and 5-HIAA in cortex, thalamus, hippocampus, and brainstem compared with naïve rats. AY-treated rats showed higher levels of 5-HIAA and 5-HT in the same brain regions, with a concomitant decrease in rates of serotonin turnover. CONCLUSIONS: The data indicate that serotonin depletion protects against experimental atypical absence seizures. The increased levels of 5-HIAA and 5-HT and altered rates of serotonin turnover suggest that the serotonergic neurotransmission may be perturbed in the AY rat.

Animals↗

PubMed2006

Human neutrophil calprotectin reduces the susceptibility of Borrelia burgdorferi to penicillin.

Borrelia burgdorferi, the spirochetal agent of Lyme disease, is susceptible to killing by a variety of polymorphonuclear leukocyte (PMN) components. Some are most effective against metabolically active B. burgdorferi. The abundant PMN cytoplasmic protein calprotectin, elevated 10- to 100-fold in inflammation, inhibits the growth of spirochetes through chelation of the essential cation, Zn. Since the action of some therapeutic antibiotics depends on bacterial division, we investigated the antibiotic sensitivities of spirochetes in calprotectin. In physiologic calprotectin, B. burgdorferi is not eliminated by therapeutic doses of penicillin G; in contrast, doxycycline is effective. Calprotectin may modify the clearance of spirochetes at sites of inflammation.

Anti-Bacterial Agents↗

PubMed2006

MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance.

Ablation of the hypothalamic peptide, melanin-concentrating hormone (MCH), leads to a lean phenotype and resistance to diet-induced obesity. Observation of MCH(-/-) mice at older ages suggested that these effects persist in mice >1 year old. Leanness secondary to caloric restriction is known to be associated with improved glucose tolerance as well as an overall increase in life span. Because the MCH(-/-) model represents leanness secondary to increased energy expenditure rather than caloric restriction, we were interested in determining whether this model of leanness would be associated with beneficial metabolic effects at older ages. To assess the effects of MCH ablation over a more prolonged period, we monitored male and female MCH(-/-) mice up to 19 months. The lean phenotype of MCH(-/-) mice persisted over the duration of the study. At 19 months, MCH(-/-) male and female mice weighed 23.4 and 30.8% less than their wild-type counterparts, a result of reduced fat mass in MCH(-/-) mice. Aged MCH(-/-) mice exhibited better glucose tolerance and were more insulin sensitive compared with wild-type controls. Aging-associated decreases in locomotor activity were also attenuated in MCH(-/-) mice. We also evaluated two molecules implicated in the pathophysiology of aging, p53 and silent inflammatory regulator 2 (Sir2). We found that expression of the tumor suppressor protein p53 was higher in MCH(-/-) mice at 9 and 19 months of age. In contrast, expression of Sir2 was unchanged. In aggregate, these findings suggest that MCH ablation improves the long-term outcome for several indicators of the aging process.

Aging↗

PubMed2005

Chronic administration of ethyl docosahexaenoate decreases mortality and cerebral edema in ischemic gerbils.

Dietary docosahexaenoic acid (DHA) intake can decrease the level of membrane arachidonic acid (AA), which is liberated during cerebral ischemia and implicated in the pathogenesis of brain damage. Therefore, in the present study, we investigated the effects of chronic ethyl docosahexaenoate (E-DHA) administration on mortality and cerebral edema induced by transient forebrain ischemia in gerbils. Male Mongolian gerbils were orally pretreated with either E-DHA (100, 150 mg/kg) or vehicle, once a day, for 4 weeks and were subjected to transient forebrain ischemia by bilateral common carotid occlusion for 30 min. The content of brain lipid AA at the termination of treatment, the survival ratio, change of regional cerebral blood flow (rCBF), brain free AA level, thromboxane B(2) (TXB(2)) production and cerebral edema formation following ischemia and reperfusion were evaluated. E-DHA (150 mg/kg) pretreatment significantly increased survival ratio, prevented post-ischemic hypoperfusion and attenuated cerebral edema after reperfusion compared with vehicle, which was well associated with the reduced levels of AA and TXB(2) in the E-DHA treated brain. These data suggest that the effects of E-DHA pretreatment on ischemic mortality and cerebral edema could be due to reduction of free AA liberation and accumulation, and its metabolite synthesis after ischemia and reperfusion by decreasing the content of membrane AA.

Animals↗

PubMed2005

Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine.

BACKGROUND: In 2003, severe acute respiratory syndrome (SARS) resulted in hundreds of infections and deaths globally. We aim to assess immunogenicity and protective efficacy of purified inactivated Vero-cell SARS vaccine in monkeys. METHODS: The cultures of SARS coronavirus (SARS-CoV) BJ-01 strain infected Vero cells were inactivated with beta-propiolactone. Sequential procedures, including ultrafiltration, gel filtration and ion exchange chromatography, were performed to obtain purified inactivated SARS vaccine. The purified SARS vaccine was analyzed with electron microscope, HPLC and Western blotting. We immunized three groups of cynomolgus macaques fascicularis with adjuvant-containing purified vaccine, purified vaccine and unpurified vaccine, respectively, and a fourth group served as a control. Antibody titers were measured by plaque reduction neutralization test. The vaccinated monkeys were challenged with SARS-CoV BJ-01 strain to observe protective efficacy. Additionally, three groups of rhesus monkeys were immunized with different doses of the purified inactivated SARS vaccine (0.5, 1 and 2mug/time/monkey) on days 0 and 7, and the monkeys were challenged with SARS-CoV GZ-01 strain. We assessed the safety of the SARS vaccine and observed whether the antibody dependent enhancement (ADE) occurred under low levels of neutralizing antibody in rhesus. FINDINGS: The purity of SARS vaccine was 97.6% by HPLC identification and reacted with convalescent sera of SARS patients. The purified SARS vaccine induced high levels of neutralizing antibodies and prevented the replication of SARS-CoV in monkeys. Under low levels of neutralizing antibody, no exacerbation of clinical symptoms was observed when the immunized monkeys were challenged with SARS-CoV. In this preliminary animal trial, no side effects were detected when monkeys were immunized with purified SARS vaccine either at normal or large doses. INTERPRETATION: The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The SARS vaccine prepared in the study appeared to be safe in monkeys.

Animals↗

PubMed2005

Room-temperature strategy for networked nonspherical gold nanostructures from Au(III)[G-2]CO2H dendrimer complex.

The present work describes a convenient approach to fabricate networked nonspherical gold nanostructures by using [G-2]CO2H dendrimer and toluene as capping and bridging agents in a CH2Cl2 and H2O biphasic system. A controlled linear assembly is achieved without the use of any catalyst at room temperature. UV-vis spectrum, transmission electron microscopy (TEM), selected area electron diffraction (SAED), and X-ray diffraction (XRD) analysis show that the product is well networked nanostructures with diameter of 4-10 nm and consists of coalesced face-centered cubic gold nanocrystals. Extended experiments reveal that both benzene and dimethylbenzene can also inhabit the gold ions to make them crosslinked, prolong the nucleation points and eventually facilitate the formation of the networks.

Journal Article↗

PubMed2005

PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma.

Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node metastasis, and ERBB2 overexpression. The fact that PIK3CA mutations and PTEN loss are nearly mutually exclusive implies that deregulated phosphatidylinositol-3,4,5-triphosphate (PIP(3)) is critical for tumorigenesis in a significant fraction of breast cancers and that loss of PIP(3) homeostasis by abrogation of either PIK3CA or PTEN relieves selective pressure for targeting of the other gene. The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution. Furthermore, the association between ERBB2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K/AKT pathway may be required to overcome intact PTEN. Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications.

Adult↗

PubMed2005

Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms.

Genetics and environment contribute to the development of obesity, in both humans and rodents. However, the potential interaction between genes important in energy balance, strain background, and dietary environment has been only minimally explored. We investigated the effects of genetic ablation of melanin-concentrating hormone (MCH), a neuropeptide with a key role in energy balance, with chow and a high-fat diet (HFD) in two different mouse strains, one obesity-prone (C57BL/6) and the other obesity-resistant (129). Substantial differences were seen in wild-type (WT) animals of different strains. 129 animals had significantly lower levels of spontaneous locomotor activity than C57BL/6; however, 129 mice gained less weight on both chow and HFD. In both strains, deletion of MCH led to attenuated weight gain compared with WT counterparts, an effect secondary to increased energy expenditure. In both strains, feeding a HFD led to further increases in energy expenditure in both WT and MCH-KO mice; however, this increase was more pronounced in 129 mice. In addition, mice lacking MCH have a phenotype of increased locomotor activity, an effect also seen in both strains. The relative increase in activity in MCH(-/-) mice is modest in animals fed chow but increases substantially when animals are placed on HFD. These studies reinforce the important role of MCH in energy homeostasis and indicate that MCH is a plausible target for antiobesity therapy.

Animals↗

PubMed2005

A new approach to highly electrooptically active materials using cross-linkable, hyperbranched chromophore-containing oligomers as a macromolecular dopant.

A new, practical approach to a variety of highly electrooptically active polymers for device development is described. It involves the use of a new thermally cross-linkable, hyperbranched oligomer containing nonlinear optical (NLO) chromophores as a macromolecular dopant in a common host polymer. A series of NLO polymeric blends were readily formulated and showed large and stable electrooptic (EO) coefficients (up to 65 pm/V). In comparison with previously studied linear NLO polyimides and guest-host polymers doped with molecular chromophores and even linear NLO analogous oligomers, this new approach offers clear advantages for device development in terms of improved poling efficiency, larger EO coefficients, good temporal stability, and versatile material formulation.

Journal Article↗

PubMed2005

Monoclonal antibodies reactive with the BAF155 (SMARCC1) and BAF170 (SMARCC2) components of human SWI/SNF-related complexes.

Mammalian SWI/SNF-related chromatin remodeling complexes are required for transcription controls that underlie differentiation, development, and tumor suppression. The complexes each consist of an ATPase of the SWI2/SNF2 family and approximately seven stably associated non-catalytic subunits. In spite of the importance of these complexes to biological processes, monoclonal antibodies to the various subunits have not been readily available. Mammalian complexes can vary in subunit composition, but the BAF155 (SMARCC1) subunit and a closely related protein, BAF170 (SMARCC2), appear to be ubiquitous components. Here we report the development of antibodies raised against a BAF155-derived peptide. The antibodies were raised against a single peptide of 18 amino acids. However, hybridomas expressing antibodies of two different specificities were isolated. One, designated DXD7, is specific for BAF155. The other, designated DXD12, is reactive with both BAF155 and BAF170. The antibodies are reactive against both native and denatured proteins, and are suitable for immunoprecipitation and Western blots. The DXD7 antibody is suitable additionally for immunofluorescence assays.

Amino Acid Sequence↗