Biomedical subjects

Xiaoping Zhang

Publications and source records attributed to Xiaoping Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Complete genome sequence of Acinetobacter bacterium strain BZX-2 isolated from hybrid sturgeon.

We report the complete genome sequence of Acinetobacter sp. strain BZX-2, isolated from a hybrid sturgeon (Acipenser baerii ♀ × Acipenser schrenckii ♂). The genome consists of a 3,819,278-bp chromosome with 3,566 predicted protein-coding genes. The genomic characteristics and antibiotic resistance genes identified provide a basis for the prevention and control of sturgeon diseases.

Acinetobacter↗

PubMed2025

Exposure to zinc oxide nanoparticles inhibits preimplantation embryonic development by disrupting zygotic genome activation.

The potential adverse effects of zinc oxide nanoparticles (ZnONPs) on human reproductive health may arise from their increasing industrial and commercial applications. However, their effects on preimplantation embryonic development and the related molecular mechanisms are still not well understood. Here, we demonstrate that ZnONPs exposure exhibit toxicity to a critical developmental period in mice. We observed that sustained exposure to ZnONPs in vitro resulted in embryonic development arrest at the 2-cell stage. To identify the susceptible stage, we controlled experiments to treat embryos with ZnONPs in the different processes of early embryonic development and determined that ZnONPs mainly to affect 2-cell stage embryos. According to the RNA-seq and EU (5-ethynyl uridine) analysis, the transcriptional activity of minor ZGA genes increased in the late 2-cell embryos following ZnONPs exposure. Subsequently, we employed multi-omics assays, including CUT&Tag and ATAC-seq. We found that ZnONPs exposure led to increased enrichment of H3K27ac (Histone H3 acetylated lysine 27) in late 2-cell embryos and enhanced chromatin accessibility, which led to abnormal upregulation of minor zygotic genome activation (ZGA) genes. In addition, the direct occupancy of ZnONPs at H3K27ac modification sites was verified through pulldown and immunoprecipitation. In conclusion, our findings demonstrate that ZnONPs exposure disrupting minor ZGA by interfering with H3K27ac erasure on the embryonic genome and ultimately impairing the developmental potential of embryos.

Animals↗

PubMed2006

Expression of Smad ubiquitin regulatory factor 2 (Smurf2) in rhesus monkey endometrium and placenta during early pregnancy.

Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that is involved in the Smad-mediated TGF-beta signaling. TGF-beta has been shown to play an important role during normal embryo implantation, but whether Smurf2 is involved in this process has not been reported. This study was first conducted to investigate the expression of Smurf2 transcript and protein in different compartments of the rhesus monkey uteri and placenta during early pregnancy. The results showed that both the cloned partial sequence of Smurf2 gene and the corresponding amino acid residues shared 99% identity with those of human homologs. On day 12 (D12) of pregnancy, strong signals of Smurf2 mRNA were found in basalis glandular epithelium and luminal epithelium, and moderate expressions were detected in functionalis glandular epithelium. During early villi stage and villi placental stage, Smurf2 mRNAs were mainly localized in the placenta villi, trophoblastic column, trophoblastic shell, and basalis glandular epithelium. There appeared strong staining signals in the arterioles on D26 of pregnancy, but faint staining signals on D18 of pregnancy. No specific staining of Smurf2 mRNA was observed in stromal cells and myometrium. The expression pattern of Smurf2 protein was generally similar to that of its mRNA. These results provide the first evidence that Smurf2 may play specific roles in glandular secretion, trophoblastic cell invasion, and placentation through mediating the expression of the related proteins of TGF-beta signaling pathway during early pregnancy.

Amino Acid Sequence↗

PubMed2006

Lexatumumab (TRAIL-receptor 2 mAb) induces expression of DR5 and promotes apoptosis in primary and metastatic renal cell carcinoma in a mouse orthotopic model.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumorigenic and transformed cell lines but not in many normal cells. Hence, TRAIL-agonist compounds have the potential of being excellent cancer therapeutic agents with minimal cytotoxicity. Here, we examine the efficacy of the TRAIL-receptor 2 agonist, lexatumumab (Human Genome Sciences, Inc., Rockville, MD), and identify molecular pathways that differentiate between lexatumumab-sensitive and lexatumumab-resistance renal cancer cells. In an orthotopic metastatic mouse model, we first demonstrate that lexatumumab was effective in reducing the tumor burden of primary and metastatic lexatumumab-sensitive xenografts. We demonstrate that lexatumumab-sensitive cells were capable of triggering both the extrinsic and the intrinsic apoptotic pathways as demonstrated by caspase 8 and caspase 9 activations, respectively, after treatment with lexatumumab. In addition, expression of c-FLIP(L) protein, an important regulator of TRAIL-induced apoptosis, decreased, while expression of the TRAIL-receptor 2, DR5, increased. This study serves as a pre-clinical model for using TRAIL-like therapies for patients with advanced RCC.

Animals↗

PubMed2006

(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.

Animals↗

PubMed2006

Uptake of cationic dyes from aqueous solution by biosorption onto granular kohlrabi peel.

A new, low cost, locally available biomaterial was tested for its ability to remove cationic dyes from aqueous solution. Granules prepared from kohlrabi peel had been utilized as a sorbent for uptake of three cationic dyes, methylene blue (MB), neutral red (NR) and acridine orange (AO). The effects of various experimental parameters (e.g., dye concentration, particle size, initial pH, contact time and other factors) were investigated and optimal experimental conditions were ascertained. Above the value of initial pH 4, three dyes studied could be removed effectively. The isothermal data fitted the Langmuir model in the case of NR sorption and the Freundlich model for all three dyes sorption. The biosorption processes followed the pseudo-first-order rate kinetics. The results in this study indicated that kohlrabi peel was an attractive candidate for removing cationic dyes from the dye wastewater.

Adsorption↗

PubMed2006

Double cohesion in structural DNA nanotechnology.

Double cohesion has proved to be a useful tool to assemble robust 2D arrays of large tiles. Here we present a variety of examples showing the utility of this approach. We apply this principle to the 3 types of 2D lattice sections of arrays whose individual tiles are inherently 3 dimensional, because they contain three vectors that span 3-space. This application includes motifs which are based on the tensegrity triangle, the six-helix bundle motif and on three skewed triple crossover molecules. All of these designs have the potential to form 3 dimensional structures if all three directions of propagation are allowed. If one direction is blunted, 2D arrays form, and all 3 combinations are presented here. In addition, a large parallelogram array that was not attainable previously using single duplex cohesion was also constructed using double cohesion. For comparison, arrays which use another type of double cohesion, double paranemic (PX) cohesion are also presented. Double cohesion of sticky ends proved to be the more effective tool to assemble large motifs into arrays.

DNA↗

PubMed2006

Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects.

BACKGROUND: Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties. RESULTS: Bioconjugates were prepared from different combinations of the approved drug, saquinavir, the antiviral agent, R.I.CK-Tat9, the polymeric carrier, poly(ethylene) glycol and the cell uptake enhancer, biotin. Anti-HIV activities were measured in MT-2 cells, an HTLV-1-transformed human lymphoid cell line, infected with HIV-1 strain Vbu 3, while parallel studies were performed in uninfected cells to determine cellular toxicity. For example, R.I.CK-Tat9 was 60 times more potent than L-Tat9 while the addition of biotin resulted in a prodrug that was 2850 times more potent than L-Tat9. Flow cytometry and confocal microscopy studies suggest that variations in intracellular uptake and intracellular localization, as well as synergistic inhibitory effects of SQV and Tat peptides, contributed to the unexpected and substantial differences in antiviral activity. CONCLUSION: Our results demonstrate that highly potent nanoscale multi-drug conjugates with low non-specific toxicity can be produced by combining moieties with anti-HIV agents for different targets onto macromolecules having improved delivery properties.

Journal Article↗

PubMed2006

In vitro panning of a targeting peptide to hepatocarcinoma from a phage display peptide library.

Phage display technology has been used as a powerful tool in the discovery of ligands specific to receptor(s) on the surface of a cancer cell and could also impact clinical issues including functional diagnosis and cell-specific drug delivery. After three rounds of in vitro panning and two rounds of reverse absorption, a group of phages capable of addressing BEL-7402 enormously were obtained for further analysis. Through a cell-based ELISA, immunofluorescence, FACS, and in vivo binding study, WP05 (sequence TACHQHVRMVRP) was demonstrated to be the most effective peptide in targeting four kinds of liver cancer cell lines (BEL-7402, BEL-7404, SMMC-7721, and HepG2), but not the normal liver cell line HL-7702. In conclusion, the peptide WP05 which was screened by in vitro phage display technology was proved to be a targeting peptide to several common hepatocellular carcinoma cell lines.

Amino Acid Sequence↗

PubMed2006

Mechanism of arsenic trioxide inhibiting angiogenesis in multiple myeloma.

In order to explore the molecular mechanism of arsenic trioxide treating multiple myeloma (MM) via inhibition of angiogenesis, the expression of brain derived neurotrophic factor (BDNF) and its specific receptor TrkB in human MM cell line KM3 and endothelial cell line ECV304 was detected by Western blotting. The angiogenic activity was evaluated by wound migration assay and tubule formation assay in vitro. The results showed that BDNF was detected in the MM cells and TrkB in the endothelial cells. Furthermore, 100 ng/mL BDNF could significantly induced endothelial cell tubule formation and wound migration. As2 O3 depressed the expression of BDNF and TrkB in the dose- and time-dependent manner. As2 O3 inhibited BDNF-induced wound migration and capillary tube formation. It was concluded that BDNF is a novel angiogenic protein as well as VEGF and has a relation with the pathogenesis of MM. As2 O3 interrupts a paracrine loop between MM cells and endothelial cells by down-regulating the TrkB expression in endothelial cells and inhibiting BDNF production in MM cells, finally resulting in inhibition of MM angiogenesis. This is probably one part of the mechanisms of the As2 O3 treating MM via the inhibition of angiogenesis.

Angiogenesis Inhibitors↗

PubMed2006

Inhibitory effects of fenofibrate on plasminogen activator inhibitor-1 expression in human endothelial cells.

The effects of fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in human umbilical endothelial cell-derived transformed cell line--ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate (0, 10, 50, 100 micromol/L) for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate (10 micromol/L), the expression levels of PAI-1 mRNA and protein were 0.65 +/- 0.05 and 0.96 +/- 0.11 respectively, significantly lower than in the control group (0.78 +/- 0.03 and 1.21 +/- 0.15, respectively, P<0.05). PAI-1 antigenic contents (24.52 +/- 8.39) in ECV304 cells treated with 10 micromol/L fenofibrate were significantly lower than those in the control group (6.98 +/- 5.12, P<0.05). It was concluded that fenofibrate inhibited the expression of PAI-1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.

Blotting, Western↗

PubMed2006

[Study on allergenicity of fresh HAM for type I hypersensitivity].

To investigate whether human amniotic membrane (HAM) preparations have the possibility to type I hypersensitivity and its allergenicity. In systemic active allergic test model, 30 guinea pigs were equally divided into three groups. Each 10 guinea pigs were immunized with fresh HAM homogenate, albumen solution (positive control) and PBS (negative control). After the animals were stimulated with corresponding allergen, observe their reaction till dying or 3 h, then obtain blood samples, to determine blood histamine concentrations using chemical fluorometry and four hemorheologic markers by hemorheology analysis system. The guinea pigs responded to fresh HAM homogenate in almost the same manner as to PBS, and no obvious allergic reaction was observed in the animals except those in positive control group. The blood histamine concentration and four hemorheologic markers showed no significant differences between HAM and PBS (P > 0.05), both were much lower than positive control group (P < 0.01). Fresh HAM won't lead to type I hypersensitivity for lack of allergen performance.

Allergens↗

PubMed2005

HIV Nef-mediated CD4 down-regulation is adaptor protein complex 2 dependent.

Nef is a crucial viral protein for HIV to replicate at high titers and in the development of AIDS. One Nef function is down-regulating CD4 from the cell surface, which correlates with Nef-enhanced viral pathogenicity. Nef down-regulates CD4 by linking CD4 to clathrin-coated pits. However, the mechanistic connection between the C-terminal dileucine motif of Nef and the component(s) of the clathrin-coated pits has not been pinpointed. In this report we used two AP-2 complex-specific inhibitors: a dominant negative mutant of Eps15 (Eps15DIII) that binds to the alpha subunit of AP-2 complex and a small interference RNA that is specific for the mu2 subunit of AP-2 complex. We show that both HIV Nef- and SIV Nef-mediated CD4 down-regulations were profoundly blocked by the synergistic effect of Eps15DIII and RNA interference of AP-2 expression. The results demonstrate that HIV/SIV Nef-mediated CD4 down-regulation is AP-2 dependent. We also show that the PMA-induced CD4 down-regulation was blocked by these two inhibitors. Therefore, PMA-induced CD4 down-regulation is also AP-2 dependent. The results demonstrate that, like the tyrosine sorting motif-dependent endocytosis (for which the transferrin receptor and the epidermal growth factor receptor are the two prototypes), dileucine sorting motif-dependent endocytosis of Nef and CD4 are also AP-2 dependent.

Adaptor Protein Complex 2↗

PubMed2005

Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription.

Triptolide has been used extensively in China for the treatment of autoimmune diseases and tumor for many centuries. Nevertheless, little is known about its exact immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether triptolide can regulate TEC activity. In this study, various cultured human and murine TECs were exposed to tumor necrotic factor-alpha (TNF-alpha) and triptolide, followed to examine the expression of B7-H1 and B7-DC. Flow cytometric analysis revealed that B7-H1 but not B7-DC constitutively expresses on TECs, and the B7-H1 protein expression was profoundly up-regulated by the stimulation of TNF-alpha with a dose-dependent manner. However, triptolide under non-cytotoxic concentration could down-regulate B7-H1 expression on activated TECs at both mRNA and protein level. This effect was transcription factor NF-kappaB dependent. Interestingly, the significant damping effect of triptolide on B7-H1 signal could promote interleukin-2 production by T cell hybridoma (C10) after antigen presentation and enhance cytokine (IFN-gamma and IL-2) secretion by anti-CD3 activated T cells. Our results indicated that triptolide could regulate TEC activity via B7-H1, in addition to previously reported it directly affects the production of some inflammatory factors by T cells, tumor cells and peripheral blood mononuclear cells.

Animals↗

PubMed2005

Population pharmacokinetics and exposure-response relationship of enfuvirtide in treatment-experienced human immunodeficiency virus type 1-infected patients.

OBJECTIVE: Our objective was to characterize population pharmacokinetics of enfuvirtide, 90 mg twice daily injected subcutaneously, in treatment-experienced human immunodeficiency virus type 1 (HIV-1)-infected patients, as well as the relationship between exposure and antiviral effect. METHODS: Plasma concentrations of enfuvirtide and HIV-1 ribonucleic acid were obtained from 628 patients in 2 phase III studies. NONMEM software was used for population pharmacokinetic analysis and to assess the effects of age, gender, body weight, anti-gp41 antibodies, and concomitant drugs. Enfuvirtide exposure (area under the plasma concentration-12-hour time curve or steady-state trough concentration) was calculated from individual parameter estimates derived from the model. The decline in HIV-1 ribonucleic acid from baseline at week 2 or 24 was regressed against estimates of enfuvirtide exposure by a maximum effect model. The exposure-response relationship was examined in functional monotherapy (phenotypic sensitivity score of 0) and combination therapy (phenotypic sensitivity score > or = 1). RESULTS: Enfuvirtide population pharmacokinetics was well described by a 1-compartment model with first-order absorption and elimination. Body weight and female gender were identified as affecting apparent clearance but not efficacy and safety. Concomitant medications had no significant effect on enfuvirtide pharmacokinetics. Antiviral response to enfuvirtide was independent of drug exposure, suggesting that the approved 90-mg twice-daily dose was in the plateau portion of the dose-response curve. For functional monotherapy (phenotypic sensitivity score of 0), approximately 66% of estimated maximal effect was achieved at week 2 and 73% at week 24, and for combination therapy, more than 92% was achieved at both weeks 2 and 24. CONCLUSIONS: Body weight and gender affected enfuvirtide clearance, but changes in exposure did not affect efficacy or safety. Efficacy reached a plateau at the 90-mg twice-daily dosage in the exposure-response curve.

Adult↗

PubMed2005

Sinomenine inhibits B7-H1 and B7-DC expression on human renal tubular epithelial cells.

Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact mechanisms of action. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether sinomenine can regulate TEC activity. In this study, cultured human TECs were exposed to proinflammatory factors interferon-gamma (IFN-gamma) and tumor necrotic factor-alpha (TNF-alpha) in presence or absence of sinomenine for 72 h, followed by analysis of surface expression of costimulatory molecules. Flow cytometric analysis revealed that various costimulatory molecules were expressed on TECs and that they were significantly up-regulated by the simulation of IFN-gamma and TNF-alpha. However, sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell. Our results indicated that sinomenine could regulate TECs activity via B7-H1 and B7-DC, in addition to previously reported its effects on some pro-inflammatory factors production by macrophages and peripheral blood mononuclear cells.

Antigens, CD↗

PubMed2005

Pharmacokinetics, pharmacodynamics and drug interaction potential of enfuvirtide.

Enfuvirtide, the first fusion inhibitor approved for the treatment of HIV-1 infection, is a synthetic peptide that binds to HIV-1 glycoprotein 41, blocking the fusion of viral and cellular membranes. When administered subcutaneously at the recommended dose of 90 mg twice daily with optimised background antiretroviral therapy, enfuvirtide significantly reduces plasma HIV-1 RNA levels up to 48 weeks compared with optimised background therapy alone. Enfuvirtide exhibits a small volume of distribution (5.48 L), low systemic clearance (1.4 L/h) and high plasma protein binding (92%). Less than 17% of enfuvirtide is converted to a minimally active deaminated form of the parent drug. Both enfuvirtide and its metabolite are primarily eliminated via catabolism to amino acid residues. Following subcutaneous administration, enfuvirtide is almost completely absorbed, and exposure increases almost linearly with dose over the range 45-180 mg. When administered at the recommended dose in adults, subcutaneous absorption is slow and protracted, resulting in relatively flat steady-state plasma concentration-time profiles. Bioavailability is high (84.3%) and the elimination half-life (3.8 hours) supports twice-daily administration. Comparable absorption was observed from three different anatomical injection sites. The pharmacokinetic-pharmacodynamic relationship indicates that the recommended dose, in combination with other active antiretrovirals, is optimal. Enfuvirtide clearance is influenced to a small extent by sex and bodyweight but this does not necessitate dosage adjustment. In vitro and in vivo studies indicate that enfuvirtide has a low potential to interact with concomitantly administered drugs. Enfuvirtide did not influence concentrations of drugs metabolised by cytochrome P450 (CYP) 3A4, CYP2D6 or N-acetyltransferase, and had only minimal effects on those metabolised by CYP1A2, CYP2E1 or CYP2C19. Coadministration of ritonavir, ritonavir-boosted saquinavir or rifampicin (rifampin) did not result in clinically significant changes in enfuvirtide pharmacokinetics. In HIV-1-infected paediatric patients, subcutaneous dosages based on bodyweight (2 mg/kg twice daily) produce pharmacokinetics broadly similar to those observed in adults administered 90 mg twice daily.

Age Factors↗

PubMed2005

Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9.

Dipeptidyl peptidase (DPP)-IV inhibitors are a new approach to the treatment of type 2 diabetes. DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies. In rats, the DPP8/9 inhibitor produced alopecia, thrombocytopenia, reticulocytopenia, enlarged spleen, multiorgan histopathological changes, and mortality. In dogs, the DPP8/9 inhibitor produced gastrointestinal toxicity. The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9. These results suggest that assessment of selectivity of potential clinical candidates may be important to an optimal safety profile for this new class of antihyperglycemic agents.

Animals↗