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Biomedical subjects

Zheng Xu

Publications and source records attributed to Zheng Xu.

At least 19 recordsLinked to original sources
PubMed2026

Quercetin, a flavonoid, suppresses viral proliferation by interfering with the ubiquitin transfer from E1 to E2 enzymes.

Quercetin is recognized for diverse pharmacological activities. However, the mechanism underlying its broad-antiviral effects has not been elucidated. Herein, we identified quercetin as a potent inhibitor of both double-stranded DNA virus Bombyx mori nucleopolyhedrovirus (BmNPV) and single-stranded RNA virus porcine reproductive and respiratory syndrome virus (PRRSV). Surface plasmon resonance (SPR) revealed that quercetin targets host ubiquitin-activating enzyme 1 (Uba1) homologs. Uba1 knockdown reduced viral proliferation and enhanced the antiviral effect of quercetin, whereas Uba1 overexpression functioned oppositely. Quercetin bound Uba1 homologs with high affinity. Notably, mutation of two binding residues, Q977 and G978, significantly disrupted the binding between BmUba1 and quercetin, and abolished quercetin's antiviral activity. Quercetin obstructed the transfer of ubiquitin from Uba1 to the E2 enzyme Ubc6, impairing the ubiquitination process. Similarly, quercetin inhibited PRRSV proliferation via targeting Uba1 in mammals. These findings elucidate the molecular mechanism underlying the pharmacological effects of quercetin, providing a theoretical basis for the development of novel antiviral agents against both DNA and RNA viruses.

Quercetin↗
PubMed2026

IL17 signaling promotes oocyte developmental competence acquisition during maturation.

BACKGROUND: Defects in the acquisition of oocyte developmental competence during the maturation process causes subfertility or infertility in animals and humans. Understanding the regulatory mechanisms of oocyte maturation is essential for reproductive biology and medicine. Follicular fluid (FF) is an important microenvironment governing oocyte maturation. METHODS: A tandem mass tags (TMT)-based comparative FF proteomic analysis was employed to identify FF proteins that are potentially crucial for oocyte maturation. A very large number of pig and mouse oocytes (approximately 20,000) and embryos (over 13,000, including somatic cell nuclear transfer, parthenogenetic activation, and in vitro fertilization embryos) were used to investigate the effects of identified FF proteins on in vitro oocyte maturation and subsequent in vitro and in vivo embryo development. RNA sequencing, quantitative PCR, enzyme-linked immunosorbent assays, and immunofluorescence were used to study the expression patterns and action mechanisms of identified FF proteins in oocytes. In addition, intra-oocyte levels of glutathione and reactive oxygen species were measured to assess redox homeostasis. RESULTS: Interleukin 17D (IL17D) was identified as an important FF protein and it is significantly upregulated in porcine FF during oocyte maturation. IL17D promotes oocyte maturation by enhancing bidirectional communication between oocytes and cumulus cells, via upregulating CX43 expression and transzonal projections, which helps to maintain oocyte redox homeostasis and nuclear-cytoplasmic synchrony. IL17D treatment of oocytes enhances subsequent in vitro and in vivo full-term embryo development by modulating lipid metabolism and histone modification reprogramming. IL17D exerts its function via activating IL17 signaling through binding to CD93. Two other IL17 family members, IL17A and IL17F, also enhance oocyte maturation quality. IL17D displays a conserved expression pattern and function in pig and mouse oocytes. CONCLUSIONS: This study reveals the critical roles of IL17D in regulating oocyte developmental competence acquisition during maturation by activating IL17 signaling. The findings provide valuable insights into the molecular mechanisms underlining oocyte developmental potential acquisition and may help to develop methods for efficient production of oocytes for assisted reproduction.

Animals↗
PubMed2007

Cap1p plays regulation roles in redox, energy metabolism and substance transport: an investigation on Candida albicans under normal culture condition.

Cap1p, a transcription factor in Candida albicans, is believed to be required for tolerance to oxidative stress. However, no information is available concerning its function on basal transcriptional profile. In this study, differentially expressed genes between the CAP1-deleted strain and its parental strain under normal culture condition were identified through microarray analysis. Notably, among the 48 down-regulated genes with the deletion of CAP1, there were three clusters, functionally related to intracellular redox, energy metabolism and substance transport. IPF7817, IPF11105 and FDH11, the three putative Cap1p target genes functionally related to redox, were shown to be activated by oxidative stress in a Cap1p-dependent manner. Furthermore, rhodamine 6G efflux analyses demonstrated that Cap1p contributed to the energy-driven efflux. Taken together, these results reveal that Cap1p plays a significant role in redox status regulation, energy metabolism and substance transport under normal culture condition.

Basic-Leucine Zipper Transcription Factors↗
PubMed2007

Fcr1p inhibits development of fluconazole resistance in Candida albicans by abolishing CDR1 induction.

Overexpression of Candida drug resistance 1 (CDR1) gene in Candida albicans (C. albicans), an efflux pump, is one of the major mechanisms contributing to drug resistance. C. albicans for fluconazole resistance 1 protein (Fcr1p) is a member of the family of zinc cluster proteins homologous to Pdr1p and Pdr3p (pleiotropic drug resistance protein) mediating azole resistance in Saccharomyces cerevisiae (S. cerevisiae) by regulating the expression of pleiotropic drug resistance 5 (PDR5) homologous to C. albicans CDR1. A previous study has showed that for fluconazole resistance 1 (FCR1) could also confer azole resistance in S. cerevisiae pdr1 pdr3 mutant by regulating PDR5. Therefore, we investigated the role of FCR1 in the development of C. albicans azole resistance in vitro and in vivo. Our results showed that Fcr1p inhibited fluconazole (FLC) resistance development in C. albicans through abolishing the induction of CDR1 expression by FLC, and in contrast FLC resistance development was accelerated resulting from the deletion of FCR1.

Animals↗
PubMed2006

Crystal structure of the SENP1 mutant C603S-SUMO complex reveals the hydrolytic mechanism of SUMO-specific protease.

SUMO (small ubiquitin-related modifier)-specific proteases catalyse the maturation and de-conjugation processes of the sumoylation pathway and modulate various cellular responses including nuclear metabolism and cell cycle progression. The active-site cysteine residue is conserved among all known SUMO-specific proteases and is not substitutable by serine in the hydrolysis reactions demonstrated previously in yeast. We report here that the catalytic domain of human protease SENP1 (SUMO-specific protease 1) mutant SENP1C(C603S) carrying a mutation of cysteine to serine at the active site is inactive in maturation and de-conjugation reactions. To further understand the hydrolytic mechanism catalysed by SENP1, we have determined, at 2.8 A resolution (1 A = 0.1 nm), the X-ray structure of SENP1C(C603S)-SUMO-1 complex. A comparison of the structure of SENP2-SUMO-1 suggests strongly that SUMO-specific proteases require a self-conformational change prior to cleavage of peptide or isopeptide bond in the maturation and de-conjugation processes respectively. Moreover, analysis of the interface of SENP1 and SUMO-1 has led to the identification of four unique amino acids in SENP1 that facilitate the binding of SUMO-1. By means of an in vitro assay, we further demonstrate a novel function of SENP1 in hydrolysing the thioester linkage in E1-SUMO and E2-SUMO complexes. The results disclose a new mechanism of regulation of the sumoylation pathway by the SUMO-specific proteases.

Amino Acid Sequence↗
PubMed2006

A biomechanical analysis of sublaminar and subtransverse process fixation using metal wires and polyethylene cables.

STUDY DESIGN: An in vitro biomechanical calf thoracic spine study. OBJECTIVE: To evaluate the biomechanical stability of sublaminar and subtransverse process fixation using stainless steel wires and ultra-high molecular weight polyethylene (UHMWPE) cables. SUMMARY OF BACKGROUND DATA: It is commonly held that transverse process fixation provides less stability than sublaminar fixation. To our knowledge, this is the first biomechanical study to compare the stability afforded by sublaminar fixation and subtransverse process fixation using metal wire and UHMWPE cable before and after cyclic loading. METHODS: There were 6 fresh-frozen calf thoracic spines (T4-T9) used to determine the sublaminar fixation stiffness and subtransverse process fixation stiffness in each group. Double strands of 18-gauge stainless steel wire, 3 and 5 mm-width UHMWPE cable (Nesplon; Alfresa, Inc., Osaka, Japan) were applied to each spine. Cyclic pure flexion-extension moment loading (2 Nm, 0.5 Hz, 5000 cycles) was applied after the initial stability was analyzed by measuring the range of motion. Statistical analyses were used to delineate differences between the various experimental groups. RESULTS: Subtransverse process wiring was more stable than sublaminar wiring after cyclic loading in flexion-extension (P < 0.05). There were no significant differences between each group in lateral bending and axial rotation after cyclic loading. Sublaminar stainless steel wiring was more stable than sublaminar 3 and 5-mm cable before and after cyclic loading in axial rotation (P < 0.01). Acute subtransverse process fixation using 3-mm cable was less stable after cyclic loading in axial rotation (P < 0.05). All other groups did not produce statistically significant differences. CONCLUSIONS: Subtransverse process fixation provides at least as much stability as sublaminar fixation. A 5-mm UHMWPE cable and stainless steel wire result in equivalent sublaminar and subtransverse process stability.

Animals↗
PubMed2006

Correlation of p53 gene mutation and expression of P53 protein in cholangiocarcinoma.

AIM: To characterize the tumor suppressor gene p53 mutations and study the correlation of p53 gene mutation and the expression of P53 protein in cholangiocarcinoma. METHODS: A total of 36 unselected, frozen samples of cholangiocarcinoma were collected. p53 gene status (exon 5-8) and P53 protein were examined by automated sequencing and immunohistochemical staining, combined with the clinical parameters of patients. RESULTS: p53 gene mutations were found in 22 of 36 (61.1%) patients. Nineteen of 36 (52.8%) patients were positive for P53 protein expression. There were significant differences in extent of differentiation and invasion between the positive and negative expression of P53 protein. However, there were no significant differences in pathologic parameters between the mutations and non-mutations. CONCLUSION: The alterations of the p53 gene evaluated by DNA sequence analysis is relatively accurate. Expression of P53 protein could not act as an independent index to estimate the prognosis of cholangiocarcinoma.

Adult↗
PubMed2006

The effects of rod contouring on spinal construct fatigue strength.

STUDY DESIGN: In vitro fatigue loading using a corpectomy model outfitted with posterior pedicle screw instrumentation. OBJECTIVE: The purpose of this study was to detect differences in fatigue resistance of titanium and stainless steel spinal constructs that use rods contoured using a French Bender, and to compare differences in fatigue resistance of contoured and straight titanium rods. SUMMARY OF BACKGROUND DATA: Instrumentation failure is generally thought to be caused by fatigue or cyclic loading. Intraoperative contouring of the posterior rods is almost always required to match the native kyphotic (thoracic) or lordotic (cervical or lumbar) spinal curvature. How bending these rods affects their overall fatigue resistance is not well described. In addition, changes in fatigue resistance may be a function of material type. METHODS: Spinal constructs were evaluated using the ASTM F1717-01 model. Two different titanium-based rods (Ti6AL4V and CpTi) and two different steel-based rods (Orthinox and 316L stainless steel) were evaluated in this study (n = 6 for each group). Rods were contoured at two points using a French Bender and were rigidly coupled to polyaxial pedicle screws within UHMWPE vertebral bodies. Constructs were cycled at a load ratio of 10 between a minimum and maximum loading regime of -250 N/-25 N and -700 N/-70 N at a frequency of 4 Hz. Estimated maximum nominal stresses at various points of interest in the spinal constructs were calculated using beam theory. Effects of the rod material, load, and stress on the number of cycles to failure were analyzed using Cox proportional hazards regression. RESULTS: All of the spinal constructs with contoured CpTi rods and contoured Ti6Al4V rods failed at one of the bends in the rods. Almost all of the spinal constructs with straight CpTi rods and straight Ti6Al4V rods failed where the blocker screw fastens the rod to the coupler of the polyaxial screw head. Contoured titanium constructs demonstrated significantly lower fatigue life than contoured 316L constructs. Contouring tended to lower the fatigue life of both the Ti6Al4V and CpTi constructs. CONCLUSION: Intraoperative rod contouring using a French Bender significantly reduces the fatigue life of titanium spinal constructs.

Bone Nails↗
PubMed2006

Overexpression of COX-2 in human osteosarcoma cells decreases proliferation and increases apoptosis.

Overexpression of cyclooxygenase-2 (COX-2) is generally considered to promote tumorigenesis. To investigate a potential role of COX-2 in osteosarcoma, we overexpressed COX-2 in human osteosarcoma cells. Saos-2 cells deficient in COX-2 expression were retrovirally transduced or stably transfected with murine COX-2 cDNA. Functional expression of COX-2 was confirmed by Northern and Western analyses and prostaglandin production. Overexpression of COX-2 reduced cell numbers by 50% to 70% compared with controls. Decreased proliferation in COX-2-overexpressing cells was associated with cell cycle prolongation in G(2)-M. Apoptosis, measured by both Annexin V binding assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining, was increased in cells overexpressing COX-2, and the increase was not reversed by treatment with NS-398, indicating that the effects were not mediated by prostaglandins. Retroviral COX-2 overexpression in two other human osteosarcoma cell lines, U2OS and TE85, also decreased cell viability. However, in the human colon carcinoma HCT-116 cell line, which is deficient in COX-2, retroviral overexpression of COX-2, at similar efficiency as in Saos-2 cells, increased resistance to apoptosis. Reactive oxygen species (ROS), measured by flow cytometry, were increased by COX-2 overexpression in Saos-2 cells but not in HCT-116 cells. Inhibition of peroxidase activity, but not of COX activity, blocked the ROS increase. Antioxidants blocked the increase in ROS and the increase in apoptosis due to COX-2 overexpression in Saos-2 cells. Our results suggest that (a) COX-2 overexpression in osteosarcoma cells may increase resistance to tumorigenesis by increasing ROS to levels that decrease cell viability and (b) the effects of COX-2 overexpression are cell type/tissue dependent.

Antioxidants↗
PubMed2006

The methyl C-H blueshift in N,N-dimethylformamide-water mixtures probed by two-dimensional Fourier-transform infrared spectroscopy.

Two-dimensional correlation spectroscopy was used to study the composition-dependent spectral variations of the CH-stretching bands of N,N-dimethylformamide (DMF)-water mixtures with X(DMF) ranging from 0.98 to 0.60. By a detailed correlation analysis of the spectral changes of the CH- and OH-stretching bands, it is found that the intensities of the CH and OH bands change in different ways when the water content is increased. It is also found that two different regions of the water content can be distinguished, in which the intensity changes have different signatures. A tentative explanation for how these phenomena might be related to structural changes in the mixture is proposed. The structural change of DMF induced by the water hydrogen bonded on the carbonyl group is supposed to be the possible origin of the methyl C-H blueshift instead of the direct C-H...O interactions before the hydrophobic hydration takes place.

Algorithms↗
PubMed2006

cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients.

Fungi have emerged as the fourth most common pathogens isolated in nosocomial bloodstream infections, and Candida albicans is the most common human fungal pathogen. Only a few antibiotics are effective in the treatment of fungal infections. In addition, the repetition and lengthy duration of fluconazole therapy has led to an increased incidence of azole resistance and treatment failure associated with C. albicans. To investigate the mechanism of drug resistance and explore new targets to treat clinically resistant fungal pathogens, we examined the large-scale gene expression profile of two sets of matched fluconazole-susceptible and -resistant bloodstream C. albicans isolates from bone marrow transplanted (BMT) patients for the first time by microarray analysis. More than 198 differentially expressed genes were identified and they were confirmed and validated by RT-PCR independently. Not surprisingly, the resistant phenotype is associated with increased expression of CDR mRNA, as well as some common genes involved in drug resistance such as CaIFU5, CaRTA2 and CaIFD6. Meanwhile, some special functional groups of genes, including ATP binding cassette (ABC) transporter genes (IPF7530, CaYOR1, CaPXA1), oxidative stress response genes (CaALD5, CaGRP1, CaSOD2, IPF10565), copper transport and iron mobilization-related genes (CaCRD1/2, CaCTR1/2, CaCCC2, CaFET3) were found to be differentially expressed in the resistant isolates. Furthermore, among these differentially expressed genes, some co-regulated with CaCDR1, CaCDR2 and CaIFU5, such as CaPDR16 and CaIFD6, have a DRE-like element and may interact with TAC1 in the promoter region. These findings may shed light on mechanisms of azole resistance in C. albicans and clinical antifungal therapy.

ATP-Binding Cassette Transporters↗
PubMed2006

Potent in vitro synergism of fluconazole and berberine chloride against clinical isolates of Candida albicans resistant to fluconazole.

In vitro interaction of fluconazole and berberine chloride was investigated against 40 fluconazole-resistant clinical isolates of Candida albicans. Synergism in fungistatic activity was found with the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed the synergistic interaction, but no antagonistic action was observed.

Antifungal Agents↗
PubMed2006

Large-scale synthesis of single crystal silver nanowires by a sodium diphenylamine sulfonate reduction process.

Silver nanowires with high aspect ratios of up to more than 60 were synthesized on a large scale by the redox reaction between silver nitrate and sodium diphenylamine sulfonate at room temperature and in the absence of surfactant and hard-template and seed. When the molar ratio of reductant sodium diphenylamine sulfonate and silver nitrate < or =1, most products were all the nanowires. When the molar ratio increases to 2:1, silver nanowires and nanobelts were concomitantly formed. The redox product N, N'-diphenylbenzidinedisulfonate and sodium diphenylamine sulfonate all play an important role in the formation of silver nanostructures. The structure, morphology, and composition of the silver nanowires were characterized by the X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive microanalysis (EDX), and UV-Vis spectroscopy respectively. High-resolution transmission microscopy (HRTEM) and selected area electron diffraction (SAED) reveal the single-crystal nature of the silver nanowires.

Benzenesulfonates↗
PubMed2006

[The emission of organic-inorganic single quantum well with organic heterojunction].

Organic-inorganic single quantum well with organic heterojunction ITO\SiO2 (60 nm)\MEH-PPV(40 nm)\Alq3 (40 nm)\SiO2 (60 nm)\Al has been fabricated. With the detailed investigation of photoluminescence and electroluminescence of this novel device, the authors found that the permittivity confinement effect and the quantum size effect have obviously an effect on the optical and electrical properties of organic-inorganic quantum well with organic heterojunction. The electroluminescence of organic-inorganic quantum well with organic heterojunction included three different emissions under alternative-current voltages: 410, 510 and 590 nm, which originated from radiative recombination of MEH-PPV, recombination of Alq3 excitons and MEH-PPV excitons respectively.

English Abstract↗
PubMed2006

[Spectral properties of energy transfer in doubly doped polymer electroluminescence].

The authors report a cascade energy transfer based on the long-range dipole-dipole Förster energy transfer between polymer and two fluorescent dyes in solid thin films. The authors studied the fabrication and emission characteristics of a new doubly doped system for color purity and energy transfer efficiency, in which two fluorescent dyes, i. e. TPB and Rubrene were doped into PVK. In the blend film, PVK acted as the energy donor, Rubrene as the fluorescent dye, and the assistant dopant TPB was used to facilitate the energy transfer from PVK to the dye Rubrene. Orange emission comes from Rubrene via a cascade energy transfer from PVK toTPB and then from TPB to Rubrene.

English Abstract↗
PubMed2006

[Study of color-changing device controlled by frequency and its mechanism].

Absorption is the underlying reason for the change in luminescence traits. And the lifetime influences the absorption in turn. This is a common law not only suitable for photoluminescence but also for other types of luminescence. In field emission display, two kinds of luminescence center have dramatically dissimilar lifetimes, which are co-doped in the same material. The spectrum changes with excitation frequency. Tuning color comes into reality in the same materials. The experiment proves that this law has something to do with lifetime, but has nothing to do with the way of excitation and the reasons for abruptly quenching.

English Abstract↗