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Biomedical subjects

Hao Xu

Publications and source records attributed to Hao Xu.

At least 37 records · Page 2Linked to original sources

Cyclooxygenase-independent effects of aspirin on HT-29 human colon cancer cells, revealed by oligonucleotide microarrays.

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation of human colon cancer cells in vitro. Transmission electron microscope detected morphological features of apoptosis in the aspirin-treated (5 mM, 72 h) HT-29 cells in which cyclooxygenoase-2 is catalytically inactive. We investigated aspirin-induced genome-wide expression changes in HT-29 cells and further studied the time- and concentration-dependent expression changes in 374 apoptosis-related genes, which is the first to show stimulation of genome-wide expression of HT-29 cells by aspirin. The most marked effects of aspirin are on ribosome assembly and rRNA metabolism, which could explain why the quasi-apoptotic morphological changes are not accompanied by a classical DNA ladder. These findings demonstrate that aspirin induces apoptosis in HT-29 cells, bolstering the hypothesis that apoptosis may be a mechanism by which NSAIDs inhibit colon carcinogenesis.

Anti-Inflammatory Agents, Non-Steroidal↗

Conserved genes in a path from commensalism to pathogenicity: comparative phylogenetic profiles of Staphylococcus epidermidis RP62A and ATCC12228.

BACKGROUND: Staphylococcus epidermidis, long regarded as an innocuous commensal bacterium of the human skin, is the most frequent cause of nosocomial infections associated with implanted medical devices. This conditional pathogen provides a model of choice to study genome landmarks correlated with the transition between commensalism and pathogenicity. Traditional investigations stress differences in gene content. We focused on conserved genes that have accumulated small mutation differences during the transition. RESULTS: A comparison of strain ATCC12228, a non-biofilm forming, non-infection associated strain and strain RP62A, a methicillin-resistant biofilm clinical isolate, revealed consistent variation, mostly single-nucleotide polymorphisms (SNPs), in orthologous genes in addition to the previously investigated global changes in gene clusters. This polymorphism, scattered throughout the genome, may reveal genes that contribute to adaptation of the bacteria to different environmental stimuli, allowing them to shift from commensalism to pathogenicity. SNPs were detected in 931 pairs of orthologs with identical gene length, accounting for approximately 45% of the total pairs of orthologs. Assuming that non-synonymous mutations would mark recent evolution, and hence be associated to the onset of the pathogenic process, analysis of ratios of non-synonymous SNPs vs synonymous SNPs suggested hypotheses about possible pathogenicity determinants. The N/S ratios for virulence factors and surface proteins differed significantly from that of average SNPs. Of those gene pairs, 40 showed a disproportionate distribution of dN vs dS. Among those, the presence of the gene encoding methionine sulfoxide reductase suggested a possible involvement of reactive oxygen species. This led us to uncover that the infection associated strain was significantly more resistant to hydrogen peroxide and paraquat than the environmental strain. Some 16 genes of the list were of unknown function. We could suggest however that they were likely to belong to surface proteins or considered in priority as important for pathogenicity. CONCLUSION: Our study proposed a novel approach to identify genes involved in pathogenic processes and provided some insight about the molecular mechanisms leading a commensal inhabitant to become an invasive pathogen.

Bacterial Proteins↗

Recognition-directed orthogonal self-assembly of polymers and nanoparticles on patterned surfaces.

We demonstrate the patterning of silica substrates with thymine (Thy-PS) and positively charged N-methylpyridinium (PVMP) polymers using photolithography and the subsequent orthogonal modification of these surfaces using diaminopyridine-functionalized polystyrene (DAP-PS) and carboxylate-derivatized CdSe/ZnS core-shell nanoparticles (COO-NP) through diamidopyridine-thymine three-point hydrogen bonding and pyridinium-carboxylate electrostatic interactions, respectively. This two-component orthogonal surface modification was accomplished in a self-sorting, single-step fashion, providing a versatile tool for the rapid and efficient creation of complex materials.

Cadmium Compounds↗

In silico discovery of human natural antisense transcripts.

BACKGROUND: Several high-throughput searches for potential natural antisense transcripts (NATs) have been performed recently, but most of the reports were focused on cis type. A thorough in silico analysis of human transcripts will help expand our knowledge of NATs. RESULTS: We have identified 568 NATs from human RefSeq RNA sequences. Among them, 403 NATs are reported for the first time, and at least 157 novel NATs are trans type. According to the pairing region of a sense and antisense RNA pair, hNATs are divided into 6 classes, of which about 87% involve 5' or 3' UTR sequences, supporting the regulatory role of UTRs. Among a total of 535 NAT pairs related with splice variants, 77.4% (414/535) have their pairing regions affected or completely eliminated by alternative splicing, suggesting significant relationship of alternative splicing and antisense-directed regulation. The extensive occurrence of splice variants in hNATs and other multiple pairing patterns results in a one-to-many relationship, allowing the formation of complex regulation networks. Based on microarray data from Stanford Microarray Database, two hNAT pairs were found to display significant inverse expression patterns before and after insulin injection. CONCLUSION: NATs might carry out more extensive and complex functions than previously thought. Combined with endogenous micro RNAs, hNATs could be regarded as a special group of transcripts contributing to the complex regulation networks.

Algorithms↗

XS0601 reduces the incidence of restenosis: a prospective study of 335 patients undergoing percutaneous coronary intervention in China.

BACKGROUND: XS0601, consisting of active ingredients (Chuangxiongol and paeoniflorin), has been shown to inhibit arterial neointimal hyperplasia in animal models and in preliminary human studies. The objective of this study was to evaluate the safety and efficacy of XS0601 in preventing restenosis following percutaneous coronary intervention (PCI). METHODS: A multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 patients were randomized into treatment with the oral administration of XS0601, or a placebo for 6 months after successful PCI. Angiographic follow-up was scheduled at 6 months, and clinical follow-ups performed at 1, 3 and 6 months after PCI. The primary end point was angiographic restenosis. The secondary end points were the combined incidence of death, target lesion nonfatal myocardial infarction, repeat angioplasty, and coronary artery bypass graft surgery. RESULTS: A total of 308 patients (91.9%) completed the study and 145 cases (47.1%) received angiographic follow-up. The restenosis rates were significantly reduced in the XS0601 group as compared with the placebo group (26.0% vs. 47.2%, P < 0.05), and the minimum lumen diameter (MLD) was greater [(2.08 +/- 0.89) mm for XS0601 vs. (1.73 +/- 0.94) mm for placebo, P < 0.05]. XS0601 also significantly reduced the combined incidence of major adverse cardiac event (10.4% in the XS0601 group vs. 22.7% in the placebo group, P < 0.05). The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in XS0601 group (7.1% and 11.0%) as compared with those in placebo group (19.5% and 42.9%) (P < 0.05). No significant side effects occurred within the 6-month follow-up period in the XS0601 group. CONCLUSION: Administration of XS0601 for 6 months is demonstrated to be safe and effective in reducing restenosis in post-PCI patients.

Adult↗

TIP30 inhibits growth of HCC cell lines and inhibits HCC xenografts in mice in combination with 5-FU.

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The specific cellular gene alterations responsible for hepatocarcinogenesis are not well known. Previous works showed that loss of TIP30, also called CC3, a putative tumor suppressor, increased the incidence of hepatocellular carcinoma in mice, and some clinical samples of human HCC tissues had aberrant expression of TIP30. Here, we report that the introduction of TIP30 by an adenovirus vector into HCC cell lines that had decreased expressions of TIP30 inhibited cell proliferation, decreased anchorage-dependent growth, suppressed invasion through the extracellular matrix, and inhibited tumorigenesis in nude mice. Moreover, exogenous expression of Tip30 sensitized HCC cells to cytotoxic drugs and to apoptosis induced by tumor necrosis factor-related ligands in vitro. Ectopic expression of TIP30 in HCC cells enhanced p53 expression and decreased Bcl-2/Bcl-xL expression. Treatment of nude mice bearing subcutaneously established HCC tumors with a combination of an adenovirus expressing TIP30 and the cytotoxic drug 5-fluorouracil completely suppressed tumor growth and prolonged survival. In conclusion, TIP30 may play an important role in the suppression of hepatocarcinogenesis by acting as a tumor suppressor. Overexpression of TIP30 might be a promising candidate as a treatment for HCC that would increase sensitivity to chemotherapeutic drugs.

Acetyltransferases↗

Nanoparticles for two-photon photodynamic therapy in living cells.

We describe here a nontoxic two-photon photodynamic nanoparticle platform and its cellular application. We demonstrate that the dye's potential toxicity can be circumvented by its permanent encapsulation into a biocompatible nanoparticle polymer matrix; this was examined by dye leaching experiments and confirmed by cell uptake experiments. Infrared two-photon nanoplatform phototoxicity was demonstrated for rat C6 glioma cells, while the controls showed no dark toxicity for these living cells.

Animals↗

[The effect of transferring adjacent non-main vessel pedicle flap on repairing the heel].

OBJECTIVE: To explore the effect of transferring adjacent non-main vessel pedicle flap on repairing the heel skin defect. METHODS: From February 2000 to April 2004, 4 kinds of flaps with non-main vessel pedicle were used to repair 30 cases of heel skin defect. Of the 30 patients, 19 were male and 11 were female, whose ages ranged from 8 to 65. Among them, 19 cases were crush injury, 5 cases were press injury, 3 cases were electric saw injury, 2 cases were osteomyelitis, and 1 case was squamous cell carcinoma. Fourteen cases were with defect area ranged from 6.0 cm x 5.5 cm to 16.5 cm x 11.0 cm. All the 14 cases were repaired with distant pedicled sural vascular flap of nutrient vessels and saphenous vascular flap of nutrient vessels. The sizes of the dissected flap ranged from 6.0 cm x 5.0 cm to 18.0 cm x 12.0 cm. And the other 16 cases with defect area ranged from 2.5 cm x 2.0 cm to 5.5 cm x 4.5 cm were repaired with foot lateral flap and foot base medial flap. The sizes of the dissected flap ranged from 4.0 cm x 3.0 cm to 8.0 cm x 7.0 cm. RESULTS: All cases were followed up for 6 to 12 months. The flaps all survived with satisfactory appearance and no ulceration. Callus appeared in 2 cases. The sense of pain and touch was partly or completely restored. The two-point discrimination sense recovered to 1.0-3.2 cm. CONCLUSION: As it is easily accessible, highly flexible and causes little damage to blood circulation, transferring adjacent non-main vessel pedicle flap, is effective in repairing foot heel skin defect.

Adolescent↗

[Clinical study on effect of xiongshao capsule on restenosis after percutaneous coronary intervention].

OBJECTIVE: To further evaluate the effect of Xiongshao Capsule (XSC) on the restenosis (RS) after percutaneous coronary intervention (PCI), based on previous clinical trials by which the preventive effect of XSC on RS after PCI has been proved. METHODS: Adopting the randomized, double-blind and placebo controlled method, the 124 patients enrolled, who were patients with coronary artery disease and received intracoronary stenting, were randomly assigned into two groups, the XSC group and the placebo control group, with 62 in each group. Six months of follow-up study was carried out on them to observe the intervention effect of XSC, which was predominantly evaluated by RS rate estimated by coronary angiography (CAG), combined with the recurrent rate of angina, clinical end-point event, and blood-stasis syndrome scores. RESULTS: Sixty two cases of 118 effective patients were followed-up with CAG for 6 months, the follow-up rate was 52.5%. The incidence of RS in the XSC group and the control group was 24.1% and 48.5% respectively, and the incidence of RS in stent in them was 14.0% and 42.0% respectively, indicating that the incidence of RS rate in the XSC group was significantly lower than that in the control group (P < 0.05). After patients had been treated for 6 months the extent of angiostenosis and diameter of the culprit arteries, determined by CAG was 26.58 +/- 20.72% and 2.21 +/- 0.85 mm in the XSC group, and 41.19 +/- 30.92% and 1.72 +/- 0.99 mm in the control group, respectively, suggesting that the extent of angiostenosis and the diameter loss were significantly reduced in the former than those in the latter, respectively (P < 0.05). The incidence of clinical end-point event was 11.7% and 27.6% in the XSC group and the control group in the 6 months' follow-up period respectively, it was significantly lower in the XSC group than that in the control group, with the P value close to statistical significance (P = 0.051). The blood-stasis syndrome scores in the XSC group was significantly lower in comparing with that in the control group after 6 months' treatment (P < 0.01). CONCLUSION: XSC can effectively prevent RS after PCI in combination with conventional Western medical treatment.

Adult↗

[Clinical observation and study of mechanisms of needle-picking therapy for primary infertility of abnormal sperm].

OBJECTIVE: To search for the best method for increasing clinical therapeutic effect on primary abnormality of sperm. METHODS: One hundred and sixty-eight cases of infertility were randomly divided into a treatment group of 85 cases and a control group of 83 cases. The treatment group were treated with needle-picking at bilateral Shengzhi points, Dicong Shenjing points and L2 Shenjing points as main. The control group were treated with oral administration of Wuzi Yanzong Pills [symbol: see text]. Their therapeutic effects were observed in 3 hospitals. RESULTS: The total effective rate of 83.5% and the pregnancy rate of the patient's wife of 78.8% in the treatment group, and corresponding figures were 54.2% and 43.4% in the control group, with a very significant difference between the two groups (P < 0.01); and reproductive hormones improved significantly after treatment in the two groups (P < 0.01); after treatment, superoxide dismulase (SOD) activity and Zn content in semen were elevated and cadmium level decreased significantly in the treatment group (P < 0.05). CONCLUSION: Needle picking therapy can significantly improve and regulate endocrine function, increase quality of semen and elevate pregnancy rate of the patient's wife for the patient of primary abnormal sperm.

Acupuncture Therapy↗

[Practical experiences of applying TCM intervention along principle of evidence-based medicine on restenosis after percutaneous coronary intervention].

As traditional Chinese medicine (TCM) attach importance to clinic, shortage of objective and quantitative criteria in evaluating therapeutic effect is one of the largest obstacles for TCM to move toward the world and win wide approval. The introduction of evidence-based medicine (EBM) concept brings favorable opportunity to research on TCM. The authors have conducted clinical studies on restenosis after percutaneous coronary intervention (PCI) intervened by TCM, in the period of Tenth Five-Year Project, and realized EBM was indeed a vital principle for clinical study on TCM. However, randomized controlled trial should be applied reasonably, attention should be paid to the standardized design of research, including estimation of sample size, concealment of randomized sequence, extension of blindness and selection of control, and stress should be put on the quality control in implementation, so as to provide objective evidence for effect evaluation of TCM treatment.

Angioplasty, Balloon, Coronary↗

[Review on treatment of unstable atherosclerotic plaque with traditional Chinese medicine].

Rupture of unstable atherosclerotic plaque is an essential pathogenetic mechanism of acute coronary syndrome (ACS), thereby, to stabilize the vulnerable plaque is of great importance for prevention and treatment of ACS. Recent study has shown the multi-target effects of traditional Chiese medicine intervention in stabilizing unstable atherosclerotic plaque is promising. The literatures involving this topic in recent years were reviewed in this paper.

Acute Coronary Syndrome↗

[Chronotropic incompetence predicts angiographic severity in patients with coronary artery disease].

OBJECTIVE: To investigate the relationship between the chronotropic incompetence and angiographic severity in patients with coronary artery disease (CAD). METHODS: Coronary angiography was performed in 130 patients suspected for CAD and angiographic severity of coronary artery was quantitated by Duke score and Gensini score. Patients were divided to 4 groups: non-CAD group (39 patients), CAD group with one coronary artery involved (CHD1 group, 30 patients), CHD group with two coronary arteries involved (CHD2 group, 31 patients) and CAD group with three coronary arteries involved (CHD3 group, 30 patients). One month before coronary angiography, symptom-limited exercise treadmill tests were made and the ratio of heart rate reserve (HRR) and the percent maximal age-predicted heart rate achieved (rHR) were measured. RESULTS: rHR and HRR were significantly lower in CHD2 group (rHR 0.79+/-0.08, HRR 0.63+/-0.11) and CHD3 (rHR 0.78+/-0.07, HRR 0.59+/-0.12) than that in non-CHD group (rHR 0.89+/-0.06, HRR 0.80+/-0.10) and CHD1 group (rHR 0.86+/-0.08, HRR 0.74+/-0.15, all P<0.05). rHR and HRR also significantly correlated with Duke score (r=-0.554, -0.578, all P<0.01) and Gennisi score (r=-0.453, -0.467, all P<0.01). CHD incidence rate was 75% in patients with positive rHR (or HRR) but without ST lowering during exercise. CONCLUSION: Chronotropic incompetence are negatively related to angiographic coronary severities and thus predict angiographic coronary severities. There is a high CAD incidence in patients with positive rHR (or HRR) but no ST lowering during symptom-limited exercise treadmill tests.

Aged↗

Molecular recognition in structured matrixes: control of guest localization in block copolymer films.

We demonstrate the use of molecular recognition to control the spatial distribution of guest molecules within block copolymer films. Block copolymers bearing recognition units were combined with complementary and noncomplementary molecules, and the extent of segregation of these molecules into the different domain types within microphase-separated thin films was quantitatively analyzed using dynamic secondary ion mass spectrometry (SIMS). Complementarity between the guest molecules and the polymer functionalities proved to be a key factor and an efficient tool for directing the segregation preference of the molecules to the different domain types. The effect of segregation preference on the glass transition temperature was studied using differential scanning calorimetry (DSC), and the results corroborate the SIMS findings. In a complementary study, guests with tunable sizes (via dendron substituents) were used to control block copolymer morphology. Morphological characterization using transmission electron microscopy (TEM) and X-ray diffraction reveal that selectivity differences can be directly translated into the ability to obtain different morphologies from recognition unit-functionalized block copolymer scaffolds.

Journal Article↗

Recognition-induced polymersomes: structure and mechanism of formation.

Random polystyrene copolymers grafted with complementary recognition elements were combined in chloroform producing vesicular aggregates, that is, recognition-induced polymersomes (RIPs). Reflection interference contrast microscopy (RICM) in solution, coupled with optical microscopy (OM) and atomic force microscopy (AFM) on solid substrates, were used to determine the wall thickness of the RIPs. Rather than a conventional mono- or bilayer structure (approximately 10 or approximately 20 nm, respectively) the RIP membrane was 43+/-7 nm thick. Structural arrangement of the polymer chains on the RIP wall were characterized by using angle-resolved X-ray photoelectron spectroscopy (AR-XPS). The interior portion of the vesicle membrane was found to be more polar, containing more recognition units, than the exterior part. This gradient suggests that a rapid self-sorting of polymers takes place during the formation of RIPs, providing the likely mechanism for vesicle self-assembly.

Journal Article↗

Effects of D-4F on vasodilation and vessel wall thickness in hypercholesterolemic LDL receptor-null and LDL receptor/apolipoprotein A-I double-knockout mice on Western diet.

Previously we showed L-4F, a novel apolipoprotein A-I (apoA-I) mimetic, improved vasodilation in 2 dissimilar models of vascular disease: hypercholesterolemic LDL receptor-null (Ldlr(-/-)) mice and transgenic sickle cell disease mice. Here we determine the mechanisms by which D-4F improves vasodilation and arterial wall thickness in hypercholesterolemic Ldlr(-/-) mice and Ldlr(-/-)/apoA-I null (apoA-I(-/-)), double-knockout mice. Ldlr(-/-) and Ldlr(-/-)/apoA-I(-/-) mice were fed Western diet (WD) with and without D-4F. Oral D-4F restored endothelium- and endothelial NO synthase (eNOS)-dependent vasodilation in direct relationship to duration of treatments and reduced wall thickness in as little as 2 weeks in vessels with preexisting disease in Ldlr(-/-) mice. D-4F had no effect on total or HDL cholesterol concentrations but reduced proinflammatory HDL levels. D-4F had no effect on plasma myeloperoxidase concentrations but reduced myeloperoxidase association with apoA-I as well as 3-nitrotyrosine in apoA-I. D-4F increased endothelium- and eNOS-dependent vasodilation in Ldlr(-/-)/apoA-I(-/-) mice but did not reduce wall thickness as it had in Ldlr(-/-) mice. Vascular endothelial cells were treated with 22(R)-hydroxycholesterol with and without L-4F. 22(R)-Hydroxycholesterol decreased NO (*NO) and increased superoxide anion (O2*-) production and increased ATP-binding cassette transporter-1 and collagen expression. L-4F restored *NO and O2*- balance, had little effect on ATP-binding cassette transporter-1 expression, but reduced collagen expression. These data demonstrate that although D-4F restores vascular endothelial cell and eNOS function to increase vasodilation, HDL containing apoA-I, or at least some critical concentration of the antiatherogenic lipoprotein, is required for D-4F to decrease vessel wall thickness.

ATP Binding Cassette Transporter 1↗