PubMed Health⌕ Search

Biomedical subjects

Hui Peng

Publications and source records attributed to Hui Peng.

At least 19 recordsLinked to original sources
PubMed2006

HIV-1-infected and/or immune activated macrophages regulate astrocyte SDF-1 production through IL-1beta.

Stromal cell-derived factor 1 alpha (SDF-1alpha) and its receptor CXCR4 play important roles in the pathogenesis of human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) by serving as a HIV-1 co-receptor and affecting cell migration, virus-mediated neurotoxicity, and neurodegeneration. However, the underlying mechanisms regulating SDF-1 production during disease are not completely understood. In this report we investigated the role of HIV-1 infected and immune competent macrophage, the principal target cell and mediator of neuronal injury and death in HAD, in regulating SDF-1 production by astrocytes. Our data demonstrated that astrocytes are the primary cell type expressing SDF-1 in the brain. Immune-activated or HIV-1-infected human monocyte-derived-macrophage (MDM) conditioned media (MCM) induced a substantial increase in SDF-1 production by human astrocytes. This SDF-1 production was directly dependent on MDM IL-1beta following both viral and immune activation. The MCM-induced production of SDF-1 was prevented by IL-1beta receptor antagonist (IL-1Ra) and IL-1beta siRNA treatment of human MDM. These laboratory observations were confirmed in severe combined immunodeficient (SCID) mice with HIV-1 encephalitis (HIVE). In these HIVE mice, reactive astrocytes showed a significant increase in SDF-1 expression, as observed by immunocytochemical staining. Similarly, SDF-1 mRNA levels were increased in the encephalitic region as measured by real time RT-PCR, and correlated with IL-1beta mRNA expression. These observations provide direct evidence that IL-1beta, produced from HIV-1-infected and/or immune competent macrophage, induces production of SDF-1 by astrocytes, and as such contribute to ongoing SDF-1 mediated CNS regulation during HAD.

AIDS Dementia Complex↗
PubMed2006

Electrotransformation of Thermoanaerobacter ethanolicus JW200.

Electrotransformation of Thermoanaerobacter ethanolicus JW200 was achieved using the plasmid, pTE16, and a pUC-based suicide vector, pTEA2. The construct pTE16 is based on the Escherichia coli-Clostridium perfringens shuttle vector pJIR715 and contains a thermostable chloramphenicol (Cm) resistance cassette. Evidence supporting transformation was provided by extracting plasmid pTE16 from presumptive transformants of T. ethanolicus and by PCR specific to the chloramphenicol acetyltransferase (cat) gene on the vector pTEA2. Transformation frequencies of plasmid pTE16 and pTEA2 were 50 +/- 7.4 and 30 +/- 4.2 transformants per mug plasmid DNA. The results provide the first unequivocal gene transfer method functional in T. ethanolicus.

Biotechnology↗
PubMed2006

Discovery of small molecule inhibitors of integrin alphavbeta3 through structure-based virtual screening.

Inhibitors of integrin alphavbeta3 have been implicated in the treatment of a variety of diseases, including tumor metastasis, neovascularization, osteoporosis, and rheumatoid arthritis. It is therefore desirable to develop new types of small molecule inhibitors of integrin alphavbeta3. Here we describe the discovery of novel classes of small molecule inhibitors, via structure-based virtual screening, that target the ligand binding site of integrin alphavbeta3. Application of the docking procedure for screening of a commercially available compound database resulted in a 1774-fold reduction in the size of the screening set (88695 to 50 compounds) and gave a hit-rate of 14% upon biological evaluation (IC50 value ranging from 30 to 200 microM). The best hit, compound 37, 3,4-dichloro-phenylbiguanide, showed inhibitory activity, in a time- and dose-dependent manner, in both cell motility and angiogenesis assays. Based on the best hit, compound 37, a more effective derivative compound 62 has been identified. Furthermore, molecular graphics analyses of a series of substituted phenylbiguanides were carried out to predict the binding mode between the active compounds and integrin alphavbeta3. Our results indicate that the substituted phenylbiguanides might be involved in the inhibition of bivalent cation-mediated ligand binding of integrin alphavbeta3.

Biguanides↗
PubMed2006

Salmeterol stimulation dissociates beta2-adrenergic receptor phosphorylation and internalization.

Salmeterol is a long-acting beta(2)-adrenergic receptor (beta(2)AR) agonist commonly used in the treatment of asthma and chronic obstructive pulmonary disease. It differs from other beta-agonists in that it has a very low intrinisic efficacy, especially when compared with the other available long-acting beta-agonist, formoterol. Receptor desensitization and down-regulation has been described with the chronic use of beta-agonists. This effect may not be the same with all beta-agonists and may be related to their stabilization of altered receptor states. The extreme hydrophobicity and high-affinity quasi-irreversible binding of salmeterol have rendered studies examining the mechanisms by which it mediates receptor desensitization, down-regulation, and internalization difficult. We determined the capacity of salmeterol to induce beta(2)AR endocytosis, G protein-coupled receptor kinase (GRK)-site phosphorylation, degradation, and beta-arrestin2 translocation in HEK293 cells as compared with other agonists of varying intrinsic efficacies. Despite stimulating GRK-mediated phosphorylation of Ser355,356 after 30 min and 18 h to an extent similar to that observed with agonists of high intrinsic efficacy, such as epinephrine and formoterol, salmeterol did not induce significant beta(2)AR internalization or degradation and was incapable of stimulating the translocation of enhanced green fluorescent protein-beta-arrestin2 chimera (EGFP-beta-arrestin2) to the cell surface. Salmeterol-induced receptor endocytosis was rescued, at least in part, by the overexpression of EGFP-beta-arrestin2. Our data indicate that salmeterol binding induces an active receptor state that is unable to recruit beta-arrestin or undergo significant endocytosis or degradation despite stimulating considerable GRK-site phosphorylation. Defects in these components of salmeterol-induced receptor desensitization may be important determinants of its sustained bronchodilation with chronic use.

Adrenergic beta-2 Receptor Agonists↗
PubMed2006

Label-free detection of DNA hybridization based on a novel functionalized conducting polymer.

A new functionalized pyrrole monomer, 3-pyrrolylacrylic acid (PAA) was synthesized. It was used to prepare a copolymer with pyrrole, poly(Py-co-PAA), which was investigated by reflective FT-IR, UV-vis spectroscopy and cyclic voltammetry. A label-free DNA sensor was prepared based on a poly(Py-co-PAA) film. Hybridization with complementary and non-complementary DNA targets was studied by electrochemical impedance spectroscopy. Results show a significant increase in the charge-transfer resistance upon addition of complementary target. The impedance spectra were analyzed by using a modified Randles and Ershler equivalent circuit model. The change in charge-transfer resistance that was used as an index of sensor response was found to be linear with logarithmic target concentration in the range of 2 x 10(-9) to 2 x 10(-7)M. The detection limit was 0.98 nM.

DNA↗
PubMed2006

TRAIL-mediated apoptosis in HIV-1-infected macrophages is dependent on the inhibition of Akt-1 phosphorylation.

HIV-1 uses mononuclear phagocytes (monocytes, tissue macrophages, and dendritic cells) as a vehicle for its own dissemination and as a reservoir for continuous viral replication. The mechanism by which the host immune system clears HIV-1-infected macrophages is not understood. TRAIL may play a role in this process. TRAIL is expressed on the cell membrane of peripheral immune cells and can be cleaved into a soluble, secreted form. The plasma level of TRAIL is increased in HIV-1-infected patients, particularly those with high viral loads. To study the effect of elevated TRAIL on mononuclear phagocytes, we used recombinant human (rh) TRAIL and human monocyte-derived macrophages (MDM) as an in vitro model. Our results demonstrated rhTRAIL-induced apoptosis in HIV-1-infected MDM and inhibited viral replication, while having a reduced effect on uninfected MDM. HIV-1 infection significantly decreased Akt-1 phosphorylation; rhTRAIL exposure further decreased Akt-1 phosphorylation. Infection with a dominant-negative Akt-1 adenovirus potentiated rhTRAIL-induced apoptosis, while constitutively active Akt-1 blocked rhTRAIL-induced apoptosis in HIV-1-infected MDM. From this data we conclude the death ligand TRAIL preferentially provokes apoptosis of HIV-1-infected MDM, and the mechanism is reliant upon the inhibition of Akt-1 phosphorylation. Understanding this mechanism may facilitate the elimination of HIV-1-infected macrophages and lead to new therapeutic avenues for treatment of HIV-1 infection.

Apoptosis↗
PubMed2006

Human memory T cell responses to SARS-CoV E protein.

E protein is a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV). Disruption of E protein may reduce viral infectivity. Thus, the SARS-CoV E protein is considered a potential target for the development of antiviral drugs. However, the cellular immune responses to E protein remain unclear in humans. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-gamma and IL-2 following stimulation with a pool of 9 peptides overlapping the entire E protein sequence. Analysis of the immune responses by flow cytometry showed that both CD4+ and CD8+T cells were involved in the SARS-CoV E-specific immune responses after stimulation with SARS-CoV E peptides. Moreover, the majority of IFN-gamma+CD4+T cells were central memory cells expressing CD45RO+CCR7+CD62L-; whereas IFN-gamma+CD8+ memory T cells were mostly effector memory cells expressing CD45RO-CCR7-CD62L-. The results of T-cell responses to 9 individual peptides indicated that the E protein contained at least two major T cell epitopes (E2 amino acid [aa] 9-26 and E5-6: aa 33-57) which were important in eliciting cellular immune response to SARS-CoV E protein in humans.

Adult↗
PubMed2006

Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients.

The role of cell-mediated immunity in human SARS-CoV infection is still not well understood. In this study, we found that memory T-cell responses against the spike (S) protein were persistent for more than 1 year after SARS-CoV infection by detecting the production of IFN-gamma using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4(+) and CD8(+) T cells were involved in cellular responses against SARS-CoV infection. Interestingly, most of SARS-CoV S-specific memory CD4(+) T cells were central memory cells expressing CD45RO(+) CCR7(+) CD62L(-). However, the majority of memory CD8(+) T cells revealed effector memory phenotype expressing CD45RO(-) CCR7(-) CD62L(-). Thus, our study provides the evidence that SARS-CoV infection in humans can induce cellular immune response that is persistent for a long period of time. These data may have an important implication in the possibility of designing effective vaccine against SARS-CoV infection, specifically in defining T-cell populations that are implicated in protective immunity.

Adult↗
PubMed2006

HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced "inside-out" signaling to extracellular matrix by preventing RhoA activation.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors exert modulatory effects on a number of cell signaling cascades by preventing the synthesis of various isoprenoids derived from the mevalonate pathway. In the present study, we describe a novel pleiotropic effect of HMG-CoA reductase inhibitors, also commonly known as statins, on vascular endothelial growth factor (VEGF)-induced type IV collagen accumulation. VEGF is an angiogenic polypeptide that is also known to play a central role in endothelial cell permeability and differentiation. Recently, VEGF has also been implicated in promoting extracellular matrix (ECM) accumulation, although the precise signaling mechanism that mediates VEGF-induced ECM expansion remains poorly characterized. Elucidation of the mechanisms through which VEGF exerts its effect on ECM is clearly a prerequisite for both understanding the complex biology of this molecule as well as targeting VEGF in several pathological processes. To this end, this study explored the underlying molecular mechanisms mediating VEGF-induced ECM expansion in mesangial cells. Our findings show that VEGF stimulation elicits a robust increase in ECM accumulation that involves RhoA activation, an intact actin cytoskeleton, and beta(1)- integrin activation. Our data also indicate that simvastatin, via mevalonate depletion, reverses VEGF-induced ECM accumulation by preventing RhoA activation.

Actin Cytoskeleton↗
PubMed2006

Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients.

The nucleocapsid (N) protein is a structural component of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and can induce antibody responses in SARS patients during infection. However, it is not known whether SARS-CoV N protein can induce a long persistence of memory T-cell response in human. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-gamma and IL-2 following stimulation with a pool of overlapping peptides that cover the entire N protein sequence. The N-specific IFN-gamma(+)CD4(+) T cells were mainly composed of CD45RA(-)CCR7(+)CD62L(-) cells, whereas IFN-gamma(+)CD8(+) memory T cells were mostly contained within CD45RA(+)CCR7(-)CD62L(-) cell population. Epitope mapping study indicated that a cluster of overlapping peptides located in the C-terminal region (amino acids [aa] 331 to 362) of N protein contained at least two different T-cell epitopes. The results indicated that human memory T-cell responses specific for SARS-CoV N protein could persist for 2 years in the absence of antigen, which would be a valuable for the design of effective vaccines against SARS-CoV and for basic studies of human T-cell memory.

CD4-Positive T-Lymphocytes↗
PubMed2006

RhoA-mediated, tumor necrosis factor alpha-induced activation of NF-kappaB in rheumatoid synoviocytes: inhibitory effect of simvastatin.

OBJECTIVE: Increasing evidence indicates that RhoA may play a central role in the inflammatory response. This study was conducted to examine the role of RhoA in mediating the activation of NF-kappaB in tumor necrosis factor alpha (TNFalpha)-stimulated rheumatoid synoviocytes, and to evaluate the modulatory effects of statins on the TNFalpha-induced activation of RhoA and NF-kappaB and the secretion of proinflammatory cytokines by rheumatoid synoviocytes. METHODS: Rheumatoid synoviocytes obtained from patients with active rheumatoid arthritis were stimulated with TNFalpha and incubated with simvastatin (SMV) (1 muM). RhoA activity was assessed by a pull-down assay. NF-kappaB DNA binding activity and nuclear translocation of NF-kappaB were measured by a sensitive multiwell colorimetric assay and confocal fluorescence microscopy, respectively. RESULTS: TNFalpha stimulation elicited a robust increase in RhoA activity in a dose-dependent manner, and SMV mitigated this increase. TNFalpha also hastened NF-kappaB nuclear translocation of subunit p65 and increased DNA binding activity, luciferase reporter gene expression, degradation of IkappaB, and secretion of interleukin-1beta (IL-1beta) and IL-6. SMV prevented the increase in NF-kappaB activation and rise in IL-1beta and IL-6 levels induced by TNFalpha, whereas mevalonate and geranylgeranyl pyrophosphate reversed the inhibitory effects of SMV on activation of NF-kappaB and RhoA. Furthermore, cotransfection with a dominant-negative mutant of RhoA demonstrated that the TNFalpha-induced signaling pathway involved sequential activation of RhoA, leading to NF-kappaB activation and, ultimately, to secretion of cytokines. CONCLUSION: This study identifies RhoA as the key regulator of TNFalpha-induced NF-kappaB activation, which ultimately results in the secretion of proinflammatory cytokines in rheumatoid synoviocytes. The findings provide a new rationale for the antiinflammatory effects of statins in inflammatory arthritis.

Aged↗
PubMed2006

Environmental factors in the development of Type 1 diabetes.

Environmental factors appear to play an important role in the pathogenesis of childhood-onset type 1 diabetes (T1D). The most important factors are thought to be infectious, dietary, perinatal, and psychosocial. Enteroviruses (especially Coxsackie B virus), breastfeeding, the early presence or lack of certain foods, birth weight, childhood over-nutrition, maternal islet autoimmunity, and negative stress events have been shown to be related to the prevalence of T1D. However, clear conclusions to date are limited because most studies lacked power to detect exposure/disease associations, were not prospective or long-term, did not start in infancy, had imprecise or infrequent exposure estimates, had confounding exposures, and failed to account for genetic susceptibility. In addition to the identification of specific antigenic triggers, several more general hypotheses, including the accelerator and hygiene hypotheses, are testable approaches worth pursuing.

Diabetes Mellitus, Type 1↗
PubMed2006

Loss of p12CDK2-AP1 expression in human oral squamous cell carcinoma with disrupted transforming growth factor-beta-Smad signaling pathway.

We examined correlations between TGF-beta1, TbetaR-I and TbetaR-II, p12(CDK2-AP1), p21(WAF1), p27(KIP1), Smad2, and p-Smad2 in 125 cases of human oral squamous cell carcinoma (OSCC) to test the hypothesis that resistance to TGF-beta1-induced growth suppression is due to the disruption of its signaling pathway as a consequence of reduced or lost p12(CDK2-AP1). Immunoreactivity for TbetaR-II decreased in OSCC with increasing disease aggressiveness; however, no differences were observed for TbetaR-I and TGF-beta1. The expression of TbetaR-II significantly correlated with p12(CDK2-AP1) and p27(KIP1) (P < .001 and P < .01, respectively). Furthermore, there was a significant relationship between TbetaR-II expression and p-Smad2 (P < .001). The in vivo correlation of the levels of TbetaR-II, p12(CDK2-AP1), and p27(KIP1) was confirmed in normal and OSCC cell lines. Additionally, in vitro analysis of TGF-beta1-treated cells showed that TGF-beta1 treatment of normal keratinocytes suppressed cell growth with upregulation of p-Smad2, p12(CDK2-AP1), and p21(WAF1) expression, whereas there was no effect on OSCC cell lines. These results provide evidence of a link between a disrupted TGF-beta-Smad signaling pathway and loss of induction of cell cycle-inhibitory proteins, especially p12(CDK2-AP1) in OSCC, which may lead to the resistance of TGF-beta1 growth-inhibitory effect on OSCC.

Aged↗
PubMed2006

Crystallization and preliminary x-ray diffraction analysis of three mastoparans.

Mastoparans are tetradecapeptides found to be the major component of wasp venoms. These peptides possess a variety of biological activities. Three related mastoparans, mastoparan from Polistes jadwagae (MP-PJ), mastoparanX (MP-X) and its carboxyl-free C-terminal form (MP-X-COO-), were crystallized. X-ray diffraction data for them were collected at resolutions of 1.2 A, 2.0 A and 3.3 A respectively.

Amino Acid Sequence↗
PubMed2006

[Expression of costimulator 4-1BBL and B7-1 on glioma cell lines].

BACKGROUND & OBJECTIVE: Costimulatory molecules 4-1BBL and B7-1 have been proposed to be therapeutic targets to improve and sustain antitumor immune response. This study was to investigate the expression of 4-1BBL and B7-1 on several glioma cell lines. METHODS: The expression of 4-1BBL and B7-1 on glioma cell lines T98G, MGR2, MGR1, SF767, SKMG1, SKMG4, and UW28 was detected by flow cytometry. The cytotoxic effects of vincristine (VCR) on the glioma cell lines were assessed with MTT assay. The correlation of 4-1BBL expression to drug resistance was analyzed. RESULTS: The 7 glioma cell lines showed various levels of 4-1BBL expression, but none expressed B7-1. The positive rate of 4-1BBL was above 30% in T98G and MGR1 cells which were resistant to VCR; while it was below 10% in MGR2, SF767, SKMG1, SKMG4, and UW28 cells which were sensitive to VCR. CONCLUSIONS: All of the detected cell lines express 4-1BBL, but none expresses B7-1. The glioma cells with high 4-1BBL expression are resistant to VCR.

4-1BB Ligand↗
PubMed2005

Cellular IAP1 regulates TRAIL-induced apoptosis in human fetal cortical neural progenitor cells.

Neural stem/progenitor cells (NPCs) are present in the developing and adult central nervous system. NPC apoptosis is an important aspect of normal brain development. We show that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 is highly expressed on human NPCs derived from fetal cortex, yet TRAIL induces only minimal levels of apoptosis in NPCs. Caspase-8 mRNA and protein, an important factor in the TRAIL-mediated death pathway, is present at low levels in human NPCs. In contrast, inhibitors of apoptosis proteins (IAP), such as c-IAP1, are highly expressed. The transcription inhibitor actinomycin D sensitized human NPCs to TRAIL-induced apoptosis. Further, inhibition of cellular inhibitors of apoptosis protein 1 (c-IAP1) expression by small interfering RNA (siRNA) increased TRAIL-mediated caspase-3 activation and apoptosis; thus, c-IAP1 protects NPCs against TRAIL-induced apoptosis and suppresses caspase-3 activation. These findings illustrate the mechanisms for NPC resistance to apoptotic agonists such as TRAIL, and demonstrate a potentially important mechanism in CNS disease states.

Apoptosis↗
PubMed2005

Cardiotrophin-1 protects cortical neuronal cells against free radical-induced injuries in vitro.

Cardiotrophin-1 (CT-1) was initially defined as a mediator of cardiomyocyte hypertrophy. Additional studies have showed that CT-1 enhanced survival of differentiated cardiac muscle cells and inhibited cardiac myocyte apoptosis after serum deprivation or cytokine stimulation. Moreover, CT-1 has recently been shown to act as a neuroregulatory cytokine in the peripheral nervous system. However, its effects in the central nervous system have not been determined. In the present study, we evaluated whether CT-1 protects cultured cortical neurons against oxidative injuries caused by the hydroxyl radical-producing agent FeSO4 and by the peroxynitrite-producing agent 3-morpholinosydnonimine (SIN-1). CT-1 reduced neuronal cell death caused by FeSO4 and also attenuated the neurotoxic effect of SIN-1 in a dose-dependent manner. These results indicate that CT-1 is neuroprotective in an in vitro model of cerebral ischemia. This study indicates that further evaluation of CT-1 in acute brain injury should be investigated in vivo.

Animals↗