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Biomedical subjects

F Zhao

Publications and source records attributed to F Zhao.

At least 19 recordsLinked to original sources

TRED: a transcriptional regulatory element database, new entries and other development.

Transcriptional factors (TFs) and many of their target genes are involved in gene regulation at the level of transcription. To decipher gene regulatory networks (GRNs) we require a comprehensive and accurate knowledge of transcriptional regulatory elements. TRED (http://rulai.cshl.edu/TRED) was designed as a resource for gene regulation and function studies. It collects mammalian cis- and trans-regulatory elements together with experimental evidence. All the regulatory elements were mapped on to the assembled genomes. In this new release, we included a total of 36 TF families involved in cancer. Accordingly, the number of target promoters and genes for TF families has increased dramatically. There are 11,660 target genes (7479 in human, 2691 in mouse and 1490 in rat) and 14,908 target promoters (10,225 in human, 2985 in mouse and 1698 in rat). Additionally, we constructed GRNs for each TF family by connecting the TF-target gene pairs. Such interaction data between TFs and their target genes will assist detailed functional studies and help to obtain a panoramic view of the GRNs for cancer research.

Animals↗

Osteogenic behavior of alginate encapsulated bone marrow stromal cells: an in vitro study.

Sodium alginate is a useful polymer for the encapsulation and immobilization of a variety of cells in tissue engineering because it is biocompatible, biodegradable and easy to process into injectable microbeads. Despite these properties, little is known of the efficacy of calcium cross-linked alginate gel beads as a biodegradable scaffold for osteogenic cell proliferation and differentiation. In this study, we investigated the ability of rabbit derived bone marrow cells (BMCs) to proliferate and differentiate in alginate microbeads and compared them with BMCs cultured in poly-L-lysine (PLL) coated microbeads and on conventional 2D plastic surfaces. Results show that levels of proliferation and differentiation in microbeads and on tissue culture plastics were comparable. Cell proliferation in microbeads however diminished after fortification with a coating layer of PLL. Maximum cell numbers observed were, 3.32 x 10(5) +/- 1.72 x 103; 3.11 x 10(5) +/- 1.52 x 10(3) and 3.28 x 10(5) +/- 1.21 x 10(3 ) for the uncoated, PLL coated and plastic surface groups respectively. Alkaline phosphatase and protein expressions reflected the stage of cell differentiation. We conclude that calcium cross-linked alginate microbeads can act as a scaffold for BMC proliferation and osteogenic differentiation and has potential for use as 3D degradable scaffold.

Alginates↗

In vitro evaluation of alginate encapsulated adipose-tissue stromal cells for use as injectable bone graft substitute.

This study aims to investigate the survival and osteogenic behavior of murine-derived adipose-tissue stromal cells (ATSCs) encapsulated in alginate microcapsules thereby instigating further studies in this cell delivery strategy for in vivo osteogenesis. Cell viability was quantified using a tetrazolium-based assay and osteogenic differentiation was evaluated by both alkaline-phosphatase (ALP) histochemistry and osteocalcin mRNA analysis. Following microencapsulation, cell numbers increased from 3.9 x 10(3) on day 1 to 7.8 x 10(3) on day 7 and maintained excellent viability in the course of 21-day culture. ALP was 6.9, 5.5, and 3.2 times higher than monolayer cultures on days 7, 14, and 21, respectively. In addition, osteocalcin mRNA was detectable in encapsulated cultures earlier (day 14) than monolayer cultures. We conclude that alginate microcapsules can act as three-dimensional matrix for ATSC proliferation and has potential for use as injectable, biodegradable scaffold in bone tissue engineering.

Adipocytes↗

ADA polymorphisms and asthma: a study in the Chinese Han population.

We have studied a sample of 120 asthmatic patients and 116 healthy control subjects from the Chinese Han population. Three polymorphic sites: ADA(1), ADA(2), and ADA(6), within the ADA gene have been examined. The proportion of carriers of *2 allele at locus ADA(1) is drastically reduced in asthmatics as compared to controls. There is an epistatic interaction of ADA(2) on the ADA(1) site characterized by a suppressive effect by the *2 allele of ADA(2) on the protective effect exerted by the *2 allele of ADA(1) site on susceptibility to asthma. Our data suggest the presence of some DNA sequences influencing the susceptibility to asthma are located in the area between ADA(1) and ADA(2) sites.

Adenosine Deaminase↗

Role of extracellular exopolymers in biological phosphorus removal.

Three sequencing batch reactors (SBRs) supplied with different carbon sources were investigated. The system supplied with glucose gained the best enhanced biological phosphorus removal (EBPR), although all of them were seeded from the same sludge. With the measurement of poly-beta-hydroxyalkanoate (PHA) concentration, phosphorus content in sludge and extracellular exopolymers (EPs) with scanning electron microscopy (SEM) combined with energy dispersive spectrometry (EDS), it was found that the biosorption effect of EPs played an important role in phosphorus removal and that the amount of PHA at the end of anaerobic phase was not the only key factor to determine the following phosphorus removal efficiency.

Adsorption↗

Inhibition of DLX4 promotes apoptosis in choriocarcinoma cell lines.

Homeodomain (HDM) proteins encoded by homeobox (HBX) genes represent a large family of transcriptional factors that control differentiation and development in certain cell types. DLX4 is a member of Distal-less (DLX) family of HBX genes. Recent studies have demonstrated that abnormal expression of DLX4 is present in several types of human tumors, such as breast cancer, leukemia and colon cancer. In the present study, we investigated DLX4 mRNA and protein expression in both normal placental tissues and human choriocarcinoma cell lines. Also, using RNA interference (RNAi) technique, we knocked down the expression of DLX4 and examined apoptosis in JEG-3 cells. Our studies demonstrated that DLX4 RNAi inhibited DLX4 mRNA expression and decreased DLX4 protein mass specifically and effectively, potentially enhancing apoptosis. Moreover, we examined expression of caspase-3 and caspase-8, and found that both caspases were increased after DLX4 knockdown. However, DLX4 RNAi did not influence Bax expression in JEG-3 cells. In conclusion, this study suggests that DLX4 may be involved in the survival of human choriocarcinoma cells, which may be mediated by the inhibition of apoptosis. The detailed mechanism needs further investigation.

Apoptosis↗

How do cancer cells acquire the fuel needed to support cell growth?

In this paper we consider whether the dependency of metazoan cells on extracellular signals to maintain cell survival results in an important barrier that must be overcome during carcinogenesis. It is now generally accepted that a major barrier to cancer comes from the inability of cells to enter and progress through the cell cycle in a cell-autonomous fashion. Most of the oncogenes studied over the last two decades contribute to the ability of the cancer cell to enter and progress through the cell cycle in the absence of the instructional signals normally imparted by extracellular growth factors. Over the last two decades, it has begun to be appreciated that there is a second potential barrier to transformation. It appears that all cells in multicellular organisms need extracellular signals not only to initiate proliferation, but also to maintain cell survival. Every cell in our body expresses the proteins necessary to execute its own death by apoptosis. A cell will activate this apoptotic program by default unless it receives signals from the extracellular environment that allow the cell to suppress the apoptotic machinery it expresses. It now appears that the molecular basis of this suppression lies in the signaling pathways that regulate cellular nutrient uptake and direct the metabolic fate of those nutrients.

Adenosine Triphosphate↗

Methemoglobinemia misdiagnosed as ruptured ectopic pregnancy.

A 22-year-old woman with an initial diagnosis of 'ruptured ectopic pregnancy' and 'hemorrhagic shock' was sent to the operation room for surgical treatment. The mucocutaneous color was deeply cyanosed and the pulse oximeter oxygen saturation (SpO2) was only 86% after tracheal intubation (100% O2). 'Chocolate-brown' blood was observed and methemoglobinemia was considered. Then the arterial blood gas (ABG) sample was obtained, an intravenous infusion of methylene blue and vitamin C followed. The patient recovered quickly, and later two other patients with similar symptoms were treated in the same way. The success was due to a correct diagnosis accompanied with prompt treatment and quick recognition of the etiology.

Adult↗

Performance of an intensive pond system treating municipal wastewater in a cold region.

A full-scale intensive pond system (IPS) with shorter HRT was designed, constructed and operated in Jining, Inner-Mongolia for the treatment of municipal wastewater, which is a mixed domestic and industrial wastewater characterized by quite high SS and lower BOD5/COD ratio values or lower biodegradability. Therefore, the pond system was designed as an integrated intensive pond system (IIPS) consisting of settling/anaerobic pond (SAP), intensified anaerobic pond (IAP), facultative pond (FP), and polishing ponds (PPs). In order to improve the performance of the IPS, some intensified measures were made, including inlet and outlet even-distribution systems of each unit pond, package of biofilm carrier in IAP for the increase and even distribution of biomass; overflow waterfalls on the dikes between unit ponds for the increase of DO in pond water, gravel filtration dike (or dam) for removing suspended solids including algae, which have improved the performance of the IPS remarkably in terms of removal of main pollutants, such as SS, COD, BOD5, TN, NH3-N, TP and total bacteria. The final effluent from the IPS in warm seasons from May to October were SS 7.2-10.8 mg/L, BOD5 8.5-19.6 mg/L, COD 44.1 - 76.5 mg/L, and NH3-N 1.5-10.2 mg/L, which well meet Chinese national discharge standard (2nd class) of secondary municipal wastewater treatment plants, i.e. BOD5 and SS 30 mg/L respectively, COD 100 mg/L, and NH3-N 25 mg/L.

Ammonia↗

Surface treatment of injectable strontium-containing bioactive bone cement for vertebroplasty.

A novel injectable bioactive bone-bonding cement (SrHAC) composed of strontium-containing hydroxyapatite (Sr-HA) as the inorganic filler and bisphenol A diglycidylether dimethacrylate (Bis-GMA) as the organic matrix for vertebroplasty was developed previously. In this study, the Sr-HA powders were surface treated with methyl methacrylate (MMA) to improve the interface integration of the two phases. After surface treatment, the compression strength and Young's modulus, which were tested after immersion in distilled water at 37 degrees C for 24 h according to ISO 5833, were increased by 68.65 % (p <.001) and 31.02% (p <.001), respectively. The bending strength and bending stiffness of the bioactive bone cement were significantly improved by 54.44% (p <.001) and 83.90% (p <.001). In addition, the handling property of the cement was also enhanced. In vitro biomechanical testing showed that the stiffness of the fractured spine recovered to 82.5% (p <.01) of the intact condition after cementation with surface-treated SrHAC. The failure load of the spine cemented with original and MMA-treated SrHAC improved by 14.25% (p <.05) and 46.91% (p <.05) in comparison with the fractured spines. Results from this study revealed that the MMA-treated SrHAC has a better mechanical effect for orthopedic applications.

Animals↗

Controllable porosity hydroxyapatite ceramics as spine cage: fabrication and properties evaluation.

A procedure was designed to prepare porosity-graded hydroxyapatite (HA) ceramics simulating the bimodal structure of natural bone, which could be used to build a cage that would promote the reconstruction of the anterior column after vertebrectomy or corpectomy in tumor and trauma surgery. HA ceramics with controllable pore size distribution and porosity were developed by using chitosan and Poly(vinyl alcohol) (PVA) as the pore-forming agents. HA ceramics with worthwhile properties such as a wide range of volume porosity (10-50%) and pore size (nanometer to 400 microm) can be obtained from this method, which allows the fabrication of HA ceramics with desirable porous characteristics simulating the bimodal natural bone architecture expected to provide advantages for bony fusion in the intervertebral foramina. When coated with chitosan-gelatin network, the bending strength of the porous HA ceramics significantly improved. The polymer network coated porous HA have potential application in the construction of cages for spinal operations.

Journal Article↗

Purification and characterization of the fusion protein trypsin-streptavidin expressed in Escherichia coli.

Expression of fusion protein trypsin-streptavidin (TRYPSA) in Escherichia coli was evaluated and the protein purified. Protein expression was induced by 1 mM isopropylthio-beta-D-galactoside (IPTG), and the enzyme activity was measured by the hydrolysis rate of p-toluenesulfonyl-L-arginine methyl ester (TAME). Expression of the fusion protein in the cell-free extract decreased with increased induction time; correspondingly, that in the inclusion bodies increased. The total expression in Luria-Bertani broth (LB) and Terrific Broth (TB) media reached the highest levels in 2 hr at 30 degrees C. The optimum expression level was 35 and 48 U/L in LB and TB, respectively. Expression of the fusion protein was verified by Western Blot analysis using streptavidin antiserum, and the fusion protein was purified using a benzamidine Sepharose 6B affinity column at room temperature. The molecular size of the soluble purified fusion protein was determined by size-exclusion chromatography using Superose 12 FPLC. A molecular weight of 39-40 kDa was obtained, indicating that the soluble protein exists as a monomer; thus, the presence of the trypsin domain must prevent the streptavidin domain from tetramer formation.

Blotting, Western↗

The Audioscan: a high frequency resolution audiometric technique and its clinical applications.

The Audioscan is a form of high definition audiometry based on iso-hearing level frequency sweeps, which was developed by Meyer-Bisch in 1990. Compared with traditional tone audiometry, it sweeps across the preset frequency range at a predetermined sweep rate and provides a continuous audiometric curve. Because the device has a maximum frequency range of 125-16 000 Hz with 64 frequencies per octave, the Audioscan method can, theoretically, give 64 times as many values as fixed-frequency audiometry, which may give greater accuracy and sensitivity. An advantage of this is its capacity to detect mild audiometric deficits such as narrow notches situated between the frequencies normally tested. These may represent very limited auditory lesions, at a stage when they cannot be detected by routine audiological methods. Thus, the Audioscan method can give not only a detailed audiometric curve, but also provide important indicators of mild auditory dysfunction. The Audioscan device (e.g. Essilor model) is commercially available for clinical purpose. It is a software-based system, which can also be used for pure tone audiometry and Békésy audiometry. This paper reviews the general aspects of the Audioscan technique and current applications for detecting auditory dysfunction. This would be valuable to provide some guidelines on the Audioscan assessment, and contribute to a clarification of the clinical application of Audioscan and facilitate further research.

Audiometry↗

Clopidogrel does not suppress blood markers of coagulation activation in aspirin-treated patients with non-ST-elevation acute coronary syndromes.

AIMS: The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study demonstrated that clopidogrel plus aspirin was superior to aspirin alone for prevention of recurrent vascular events in patients with acute coronary syndromes. The aim of this study was to compare the effect of these two regimens on biochemical markers of platelet and coagulation activation. METHODS AND RESULTS: We studied 485 patients with non-ST-elevation acute coronary syndrome who were randomized to clopidogrel (300 mg loading dose followed by 75 mg daily) or placebo for a period of 3-12 months. All patients also received aspirin (recommended dose 75-325 mg daily). Blood levels of P-selectin, prothrombin fragment F1.2, D-dimer, and von Willebrand factor were measured at baseline, day 7 (or hospital discharge), and at day 30 after randomization. Patients receiving clopidogrel plus aspirin compared with aspirin alone had similar baseline geometric mean plasma levels of P-selectin (50.2 vs 51.7 ng.ml(-1), P=0.45), prothrombin fragment F1.2 (1.13 vs 1.12 nmol.l(-1), P=0.94), D-dimer (467 vs 460 ng.ml(-1), P=0.85), and von Willebrand factor levels (1.89 vs 1.85 U.ml(-1), P=0.59) and there also were no significant differences at day 7, or day 30. However, compared with baseline, there was a significant rise in prothrombin fragment F1.2 at day 7 (from 1.12 to 1.39 nmol.l(-1), P<0.0001) and day 30 (from 1.12 to 1.44 nmol.l(-1), P<0.0001), and D-dimer at day 7 (from 464 to 539 nmol.l(-1), P<0.0001) and day 30 (from 464 to 576 nmol.l(-1), P<0.0001). The magnitude of this rise appeared to be greatest in patients who experienced the primary outcome, a composite of cardiovascular death, myocardial infarction, stroke, or refractory ischaemia by the end of the study. P-selectin levels were not elevated at any time point but von Willebrand factor values were elevated at baseline and remained elevated at days 7 and 30. CONCLUSION: Our results indicate that the clinical benefits of clopidogrel are not associated with a parallel reduction in markers of coagulation activation. Early suppression of coagulation markers most likely reflects the effects of heparin. The persistence of thrombin generation despite long-term clopidogrel and aspirin therapy suggests that even more intensive antithrombotic therapy may be required in these patients.

Antigens↗

Influence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small-cell lung cancer.

We attempted to investigate immunohistochemical expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PD-ECGF), c-erbB-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 using surgical specimens of 119 non-small-cell lung carcinoma (NSCLC) cases and to evaluate the relationship between the expression levels of each molecule and clinicopathological factors or prognosis. VEGF expression levels were significantly associated with the local invasion (P = 0.0001), lymph node involvement (pN-factor) (P = 0.0019), pathological stage (p-stage) (P = 0.0027) and lymphatic permeation (P = 0.0389). PD-ECGF expression levels were associated with pN-factor (P = 0.0347). MMP-2 expression levels were associated with pN-factor (P = 0.004) and lymphatic permeation (P = 0.0056). Also, MMP-9 expression levels showed a significant correlation to local invasion (P = 0.0012), pN-factor (P = 0.0093) and p-stage (P = 0.0142). Multivariate analysis showed VEGF to be the most related to local invasion (P = 0.0084), and MMP-2 was the only factor with significant independent impact on lymphatic permeation (P = 0.0228). Furthermore, log-rank analysis showed significant association with poor survival by VEGF, bFGF, MMP-2 and MMP-9. Especially, combined overexpression of VEGF and MMP-2 revealed poor prognosis, our study might provide a basis for the better evaluation of biological characteristics and a new therapeutic strategy based on chemotherapy.

Adult↗

Cloning and characterization of a novel mouse AP-2 transcription factor, AP-2delta, with unique DNA binding and transactivation properties.

AP-2 transcription factors are sequence-specific DNA-binding proteins expressed in neural crest and other tissues during mammalian development. Three mammalian genes, AP-2alpha, AP-2beta, and AP-2gamma, have been reported previously. A partial predicted AP-2 gene was identified in tandem with AP-2beta on human chromosome 6p12-p21.1. The orthologous mouse gene, which we named Ap-2delta, was identified from a fetal mouse head cDNA library. Northern analysis revealed two transcripts in embryonic and newborn mouse brain, with markedly higher steady-state levels in the former. The predicted Ap-2delta protein comprised 452 amino acids and was highly similar to other AP-2 proteins across the DNA-binding and dimerization domains. Ap-2delta formed homodimers and heterodimers in vitro, bound an optimized AP-2 consensus DNA sequence, and transactivated gene expression in eukaryotic cells. Ap-2delta dimers bound poorly to an AP-2 binding sequence from the human metallothionein IIa promoter in vitro, revealing a sequence specificity not previously observed among other AP-2 proteins. The PY motif and critical residues in the transactivation domain, which are highly conserved in the AP-2 family and believed necessary for transactivation, were divergent in Ap-2delta. The unique protein sequence and functional features of Ap-2delta suggest mechanisms, besides tissue-specific AP-2 gene expression, for specific control of target gene activation.

Amino Acid Sequence↗

Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.

BACKGROUND: Despite the use of aspirin, there is still a risk of ischaemic events after percutaneous coronary intervention (PCI). We aimed to find out whether, in addition to aspirin, pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI. METHODS: 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been randomly assigned double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission, and for a median of 10 days overall. After PCI, most patients (>80%) in both groups received open-label thienopyridine for about 4 weeks, after which study drug was restarted for a mean of 8 months. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI. The main analysis was by intention to treat. FINDINGS: There were no drop-outs. 59 (4.5%) patients in the clopidogrel group had the primary endpoint, compared with 86 (6.4%) in the placebo group (relative risk 0.70 [95% CI 0.50-0.97], p=0.03). Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death, myocardial infarction, or any revascularisation (p=0.03), and of cardiovascular death or myocardial infarction (p=0.047). Overall (including events before and after PCI) there was a 31% reduction cardiovascular death or myocardial infarction (p=0.002). There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group (p=0.001). At follow-up, there was no significant difference in major bleeding between the groups (p=0.64). INTERPRETATION: In patients with acute coronary syndrome receiving aspirin, a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events, compared with placebo.

Aged↗

Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.

BACKGROUND: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients. METHODS: We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months. RESULTS: The first primary outcome--a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary outcome or refractory ischemia--occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent). CONCLUSIONS: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.

Acute Disease↗