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Biomedical subjects

Yi Zhu

Publications and source records attributed to Yi Zhu.

At least 37 records · Page 2Linked to original sources
PubMed2006

Prostaglandin A1 inhibits increases in intracellular calcium concentration, TXA(2) production and platelet activation.

AIM: In our previous studies we found that cyclopentenane prostaglandin A1 (PGA1) had neuroprotective effects in a rodent ischemic model. In the present study we aimed to investigate the inhibitory effect of PGA1 on platelet function. METHOD: The rate of aggregation of human platelets was measured by using turbidimetry. The rate of adhesion of platelets to cultured endothelial cells was determined by using [(3)H]-adenine labeled platelets. 5-Hydroxytryptamine release from platelets was measured with O-phthaldialdehyde fluorospectrophotometry. The levels of TXB(2), a stable metabolite of TXA(2), were determined by radioimmuno-assay. Alternations in platelet morphology were observed using an electron microscope, and the intraplatelet free calcium concentrations were measured with Fluo-3/AM FCM assay. RESULTS: PGA1 significantly inhibited thrombin-, collagen- and ADP-induced aggregation and adhesion of platelets. The morphological changes of platelets induced by thrombin were blocked by PGA1. PGA1 inhibited the release of 5-hydroxytyptamine from dense granules and the synthesis of TXA(2). CONCLUSION: PGA1 inhibits the activation of platelets probably through blocking increases in intracellular calcium concentration and TXA(2) synthesis.

Adenosine Diphosphate↗
PubMed2006

[Study on concentration modulation spectra of the molecular ion beam by AC glow discharge].

An experimental apparatus using an AC discharge was developed for producing molecular ion beam. The emission spectral intensity of N2+ is stronger than that of N2, and a very high ratio of N2+ (B)/N2 (C) up to 6:1, was achieved in N2 discharge. The effects and processes of N2 discharge, and the concentration modulation spectra were studied. The vibrational temperature and rotational temperature of N2+ molecular ions beam were calculated to be 3 310 and 282 K respectively from the emission spectra.

English Abstract↗
PubMed2006

[Reproduction of severe asthma model in mice].

OBJECTIVE: To reproduce a severe asthma model in ovalbumin (OVA)-sensitized Balb/C mice by induction with respiratory syncytial virus (RSV). METHODS: Thirty Balb/C mice were randomly divided into phosphate buffer solution (PBS) control group, OVA group and OVA/RSV group. The severe asthma model was reproduced by sensitization with intraperitoneal injection of OVA, followed by repeated inhalation of OVA combined with repeated intranasal instillation of RSV (1.0x10(9) pfu/L in 50 microl). Asthmatic symptoms were observed. The changes in airway responsiveness represented by lung resistance (R(L)) stimulated by acetylcholine (Ach) and function of lung in terms of peak expiratory flow (PEF) and the ratio of forced expiratory volume in 0.4 second (FEV 0.4) /forced vital capacity (FVC) were determined. Lung tissue sections with hematoxylin and eosin (HE) staining for general pathology, periodic acid Schiff (PAS) staining for identification of goblet cells mucus secretion and Masson staining for pathologic changes in lung tissue and remodeling were examined. The ratio of inner diameter to outer diameter of the airway, and the thickness of smooth muscle and basement membrane were determined. RESULTS: (1) The differences in R(L), PEF and ratio of FEV 0.4 /FVC both in OVA/RSV group and OVA group were significant when compared with those in PBS control group when stimulated by Ach (5.0, 15.0 and 45.0 g/L) (respectively P<0.01). Asthma symptoms were more severe in OVA/RSV group, compared with those of OVA group. Total R(L) was increased and PEF and ratio of FEV 0.4 /FVC were decreased in OVA/RSV group compared with those of OVA group (respectively P<0.01). There were more severe bronchoconstriction and more extensive inflammatory cells (eosinophils, lymphocytes, neutrophils) infiltration around the bronchi in the OVA/RSV group. A marked and extensive airway goblet cell hyperplasia and mucus excretion in airway lumen and deposition of collagen in subepithelial basement membrane were found in the OVA/RSV group. (2) The ratio of inner diameter to outer diameter and that of the thickness of smooth muscle and basement membrane were 0.56+/-0.03, (45.12+/-2.08) microm and (36.15+/-1.88) microm, respectively, in OVA/RSV group, and the differences were significant (respectively P<0.01), as compared with OVA group [0.75+/-0.06, (24.63+/-0.94) microm and (21.68+/-1.13) microm, respectively]. CONCLUSION: An animal model of severe asthma is successfully reproduced by nasal inoculation with RSV in OVA-sensitized Balb/C mice.

Animals↗
PubMed2005

The antiinflammatory effect of laminar flow: the role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase.

We previously reported that laminar flow activates peroxisome proliferator-activated receptor gamma (PPARgamma) in vascular endothelial cells in a ligand-dependent manner that involves phospholipase A2 and cytochrome P450 epoxygenases. In this study, we investigated whether epoxyeicosatrienoic acids (EETs), the catalytic products of cytochrome P450 epoxygenases, are PPARgamma ligands. Competition and direct binding assays revealed that EETs bind to the ligand-binding domain of PPARgamma with K(d) in the microM range. In the presence of adamantyl-ureido-dodecanoic acid (AUDA), a soluble epoxide hydrolase (sEH)-specific inhibitor, EETs increased PPARgamma transcription activity in endothelial cells and 3T3-L1 preadipocytes. Inclusion of AUDA in the perfusing media enhanced, but overexpression of sEH reduced, the laminar flow-induced PPARgamma activity. Furthermore, laminar flow augmented cellular levels of EETs but decreased sEH at the levels of mRNA, protein, and activity. Blocking PPARgamma by GW9662 abolished the EET/AUDA-mediated antiinflammatory effect, which indicates that PPARgamma is an effector of EETs.

3T3-L1 Cells↗
PubMed2005

Upregulation of aldose reductase by homocysteine in type II alveolar epithelial cells.

Homocysteine (Hcy) has recently been recognized as an integral component of several disorders. However, the association between hyperhomocysteinemia (HHcy) and pulmonary disease is not well understood. The combination of two-dimensional electrophoresis and tandem mass spectrometry detected and identified proteins that are differentially expressed in human type II alveolar epithelial cells (A549 cells) treated by Hcy. We found that aldose reductase (AR) showed more abundant expression in the cells. Further, Hcy (100-500microM) could induce a time- and dose-dependent upregulation of AR protein levels. Immunohistochemical staining of cross-sections from HHcy mice lungs also revealed increased expression of AR protein. Intracellular levels of reactive oxygen species (ROS) were remarkably elevated in A549 cells treated with Hcy. Pretreatment of A549 cells with catalase and SOD significantly suppressed the Hcy-induced AR expression, which suggests the involvement of ROS in this process. The major signaling pathway mediating the upregulation of AR was demonstrated to be the Ras/Raf/ERK1/2 pathway. In addition, Hcy might reduce surfactant protein B (SP-B) expression in the cells, which could be significantly attenuated by Alrestatin, an AR inhibitor, indicating a damaging role of Hcy-induced AR elevation in the lung. These results show a novel and unanticipated link between HHcy and AR upregulation that may be a risk factor in pulmonary disease of patients with HHcy.

Aldehyde Reductase↗
PubMed2005

Adenovirus-mediated overexpression of novel mutated IkappaBalpha inhibits nuclear factor kappaB activation in endothelial cells.

BACKGROUND: Nuclear factor kappaB (NF-kappaB) overactivation, requiring phosphorylation and degradation of its inhibitor IkappaBalpha, is the basis for chronicity of airway inflammation in asthma. Based on our previous plasmid pShuttle-IkappaBalpha, carrying an IkappaBalpha gene from human placenta, we optimized a novel IkappaBalpha mutant (IkappaBalphaM) gene, constructed and characterized its replication-deficient recombinant adenovirus (AdIkappaBalphaM), and tested whether AdIkappaBalphaM-mediated overexpression of IkappaBalphaM could inhibit the NF-kappaB activation in endothelial cells. METHODS: IkappaBalphaM gene (203 - 1003 bp) encoding 267 amino acids, acquired by site-directed deleting N-terminal phosphorylation sites of serine 32/36, was subcloned into the pShuttle and pGEM-T vectors for further polymerase chain reaction (PCR), restriction digestion, deoxyribonucleic acid (DNA) sequencing and homology analyses. Subsequent to inserting the expression unit of pShuttle-IkappaBalphaM, containing cytomegalovirus (CMV) promoter, IkappaBalphaM complementary DNA (cDNA) and polyadenylic acid (PolyA) signals, into the type 5 adenovirus (Ad5) vector, the resultant AdIkappaBalphaM was packaged in human embryonic kidney (HEK) 293 cells by cotransfection with lipofectamine. Western blot analysis and electrophoretic mobility shift assay were utilized to detect the AdIkappaBalphaM-mediated overexpression of IkappaBalphaM in HEK293 cells and its suppressive effect on phorbol 12-myristate 13-acetate (PMA)-induced NF-kappaB activation in human umbilical vein endothelial (ECV304) cells, respectively. RESULTS: The relevant nucleotides and deduced amino acids of 801 bp IkappaBalphaM gene were consistent with those of IkappaBalpha gene (GenBank accession number: M69043). The titer of the prepared AdIkappaBalphaM was 4.0 x 10 (12) plaque-forming units (pfu)/L. Moreover, the IkappaBalphaM gene was overexpressed in HEK293 cells, and potently inhibited the PMA-induced NF-kappaB activation in ECV304 cells dose-dependently. CONCLUSIONS: AdIkappaBalphaM is a novel vector for both efficient transfer and specific overexpression of IkappaBalphaM gene, as well as potent inhibition of NF-kappaB activity, providing a promising strategy for gene therapy of asthma.

Adenoviridae↗
PubMed2005

Oxidized LDL downregulates ATP-binding cassette transporter-1 in human vascular endothelial cells via inhibiting liver X receptor (LXR).

OBJECTIVE: ATP-binding cassette transporter-1 (ABCA1) mediates the active efflux of cholesterol and phospholipids, playing an important role in cholesterol homeostasis and atherogenesis. Oxidized low density lipoprotein (oxLDL) is an atherogenic molecule associated with the vascular endothelial dysfunction and development of atherosclerotic plaque. This report describes the effect of copper-catalyzed oxLDL on the regulation of ABCA1 in human endothelial cells (ECs). METHODS AND RESULTS: oxLDL downregulated ABCA1 at both mRNA and protein levels in a dose-dependent manner. This inhibitory effect of oxLDL was observed with both minimally and extensively oxLDL. Transfection of the ABCA1 promoter luciferase revealed oxLDL to substantially decrease ABCA1 promoter activity at basal conditions and after stimulation by overexpressing the liver X receptor LXRalpha and retinoid X receptor RXRalpha. oxLDL also attenuated LXR activation by blocking LXR ligand binding and interfering with the generation of 27-hydroxycholesterol, an LXR endogenous ligand. Furthermore, oxLDL inhibited exogenous cholesterol- and oxysterol-induced endothelial ABCA1 induction. CONCLUSION: oxLDL downregulated ABCA1 by inhibiting LXR activation in endothelial cells. Such an effect may contribute to endothelial dysfunction and plaque formation.

ATP Binding Cassette Transporter 1↗
PubMed2005

Diuresis and natriuresis caused by activation of VR1-positive sensory nerves in renal pelvis of rats.

To test the hypothesis that activation of the vanilloid receptor 1 (VR1) expressed in sensory nerves innervating the renal pelvis leads to diuresis and natriuresis, a selective VR1 receptor agonist, capsaicin (2.4 nmol), or vehicle was perfused intravenously or into the left renal pelvis of anesthetized rats at a rate without changing renal perfusion pressure. Mean arterial pressure was not altered by capsaicin administered intravenously or into the renal pelvis. Capsaicin perfusion into the left renal pelvis but not intravenously caused significant increases in urine flow rate and urinary sodium excretion bilaterally in a dose-dependent manner, which were abolished by capsazepine, a selective VR1 receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral renal denervation. Capsaicin given intravenously or into the left renal pelvis increased plasma calcitonin gene-related peptide levels to the same extent. Increased plasma calcitonin gene-related peptide levels induced by capsaicin (68.9+/-2.8 pg/mL) perfusion into the renal pelvis was prevented either by capsazepine (22.5+/-10.1 pg/mL) given ipsilaterally into the renal pelvis or by ipsilateral renal denervation (25.9+/-2.3 pg/mL). Taken together, our data show that unilateral activation of VR1-positive sensory nerves innervating the renal pelvis leads to bilateral diuresis and natriuresis via a mechanism that is independent of plasma calcitonin gene-related peptide levels. These data suggest that VR1-positive sensory nerves in the kidney enhance renal excretory function, a mechanism that may be critically involved in sodium and fluid homeostasis.

Animals↗
PubMed2005

Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss.

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here a systematic mutational screening of the mitochondrial 12S rRNA gene in 128 Chinese pediatric subjects with sporadic aminoglycoside-induced and non-syndromic hearing loss. We show that aminoglycoside ototoxicity accounts for 48% of cases of hearing loss in this Chinese pediatric population. Of the known deafness-associated mutations in this gene, the incidence of the A1555G mutation is approximately 13% and approximately 2.9% in this Chinese pediatric population with aminoglycoside-induced and non-syndromic hearing loss, respectively. Furthermore, mutations at position 961 in the 12S rRNA gene account for approximately 1.7% and 4.4% of cases of aminoglycoside-induced and non-syndromic hearing loss in this Chinese clinical population, respectively. The T1095C mutation has been identified in one maternally inherited family with aminoglycoside-induced and non-syndromic hearing loss. However, the C1494T mutation was not detected in this clinical population. In addition, three variants, A827G, T1005C and A1116G, in the 12S rRNA gene, localized at highly conserved sites, may play a role in the pathogenesis of aminoglycoside ototoxicity. These data strongly suggest that the mitochondrial 12S rRNA is a hot-spot for deafness-associated mutations in the Chinese population.

Adolescent↗
PubMed2005

[The study on platelet-derived growth factor and proliferating cell nuclear antigen antisense oligodeoxynucleotides together inhibiting the stenosis of transplanted vascular].

OBJECTIVE: To study the effect of platelet-derived growth factor (PDGF) and proliferating cell nuclear antigen (PCNA) antisense oligodeoxynucleotides (AODN) together on inhibiting the proliferation of the stenosis of transplanted vascular. METHODS: The left and right external iliac arteries (length 1.0 cm) of rabbits were transplanted reciprocally. The transplanted vascular were respectively soaked in liposomes, PDGF-AODN, PCNA-AODN and PDGF-AODN adding PCNA-AODN solution about 20 minute, the vascular anastomotic were sutured by 8/0 suture of soaked in AODN solution. Four weeks later, the specimens were harvested for microscopy. The pathological morphology of transplanted vascular were observed under microscope (HE). The intimal thickness and area, stenosis ratio(%) of transplanted vascular were calculate and analysed statistically among group by computer system. The number of positive cells of PDGF's mRNA in transplanted vascular wall were counted with in situ hybridization histo-cytochemistry and the number of positive cells of PCNA's protein in transplanted vascular wall were counted by S-P immunochemistry. RESULTS: The intimal thickness and area, stenosis ratio of transplanted vascular, the number of PDGF and PCNA positive cell in PDGF-AODN adding PCNA-AODN group were significantly lower than those in other group (P < 0.01), and that were lower evidently than PDGF-AODN group and PCNA-AODN group. CONCLUSION: PDGF and PCNA antisense oligodeoxynucleotides together could significantly inhibit the proliferation of vascular smooth muscle cell and stenosis of transplanted vascular.

Animals↗
PubMed2005

Neuroprotective effects of prostaglandin A1 in animal models of focal ischemia.

The present study evaluated the neuroprotective potential of prostaglandin A1 (PGA1) in rodent models of focal cerebral ischemia. PGA1 33 nmol reduced infarction volume by about 43% (P < 0.05) when administered intracerebroventricularly before and after transient ischemia in mice. PGA1 16.5-66 nmol diminished infarction volume by 18% to 27% (P < 0.01) when administered immediately following permanent ischemia in rats. PGA1 treatment also significantly ameliorated motor dysfunction after brain ischemia. These results suggest that PGA1 protects neurons from ischemic injury.

Analysis of Variance↗
PubMed2005

Role of dual-site phospholamban phosphorylation in intermittent hypoxia-induced cardioprotection against ischemia-reperfusion injury.

Cardioprotection by intermittent high-altitude (IHA) hypoxia against ischemia-reperfusion (I/R) injury is associated with Ca(2+) overload reduction. Phospholamban (PLB) phosphorylation relieves cardiac sarcoplasmic reticulum (SR) Ca(2+)-pump ATPase, a critical regulator in intracellular Ca(2+) cycling, from inhibition. To test the hypothesis that IHA hypoxia increases PLB phosphorylation and that such an effect plays a role in cardioprotection, we compared the time-dependent changes in the PLB phosphorylation at Ser(16) (PKA site) and Thr(17) (CaMKII site) in perfused normoxic rat hearts with those in IHA hypoxic rat hearts submitted to 30-min ischemia (I30) followed by 30-min reperfusion (R30). IHA hypoxia improved postischemic contractile recovery, reduced the maximum extent of ischemic contracture, and attenuated I/R-induced depression in Ca(2+)-pump ATPase activity. Although the PLB protein levels remained constant during I/R in both groups, Ser(16) phosphorylation increased at I30 and 1 min of reperfusion (R1) but decreased at R30 in normoxic hearts. IHA hypoxia upregulated the increase further at I30 and R1. Thr(17) phosphorylation decreased at I30, R1, and R30 in normoxic hearts, but IHA hypoxia attenuated the depression at R1 and R30. Moreover, PKA inhibitor H89 abolished IHA hypoxia-induced increase in Ser(16) phosphorylation, Ca(2+)-pump ATPase activity, and the recovery of cardiac performance after ischemia. CaMKII inhibitor KN-93 also abolished the beneficial effects of IHA hypoxia on Thr(17) phosphorylation, Ca(2+)-pump ATPase activity, and the postischemic contractile recovery. These findings indicate that IHA hypoxia mitigates I/R-induced depression in SR Ca(2+)-pump ATPase activity by upregulating dual-site PLB phosphorylation, which may consequently contribute to IHA hypoxia-induced cardioprotection against I/R injury.

Altitude↗
PubMed2005

A recurrent duodenal gastrointestinal stromal tumor with a frameshift mutation resulting in a stop codon in KIT exon 13.

Gastrointestinal stromal tumors (GISTs) are a specific and rare subset of human gastrointestinal tract tumors. Most GISTs show gain-of-function mutations of KIT, mainly in exon 11, that always maintain the reading frame. We report on data from a 43-year-old Japanese man with recurrent duodenal GIST and a frameshift mutation in KIT exon 13 together with an in-frame deletion in KIT exon 11 detected by genomic DNA sequencing. Deletion of 48 base pairs of KIT exon 11, which preserved the reading frame, was identified in both primary and recurrent tumors, whereas deletion of one nucleotide of codon 642 of KIT exon 13, which changed the reading frame and induced a novel stop codon at amino acid 644, was found only in the recurrent tumor. The predicted protein resulting from the latter would lack part of the kinase domain. To the best of our knowledge, this is the first documentation of a GIST with a frameshift mutation of KIT.

Adult↗
PubMed2005

Analysis of class switch recombination and somatic hypermutation in patients affected with autosomal dominant hyper-IgM syndrome type 2.

Autosomal recessive form of hyper-IgM syndrome type 2 (AR-HIGM2) is secondary to mutations affecting both alleles of AICDA gene encoding activation-induced cytidine deaminase, characterized by defects of immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) in most of the patients. We herein report the immunological phenotype of seven patients carrying a single heterozygous R190X mutation in AICDA. Variable defect in in vivo CSR inherited as an autosomal dominant (AD) trait strongly suggests that this heterozygous AICDA mutation causes HIGM (AD-HIGM2). In AD-HIGM2 B cells, CSR was consistently found impaired in vitro. However, in contrast to AR-HIGM2, the CSR-induced double-stranded DNA breaks in the switch region of IgM heavy chain gene were detected. The SHM frequency in V regions of IgM heavy chain gene in B cells was normal in all (but one patient). The characteristics of the AD-HIGM2 phenotype indicate that the AID C-terminal region may be involved in DNA repair machinery required for CSR.

Adolescent↗
PubMed2005

Analysis of serum soluble CD40 ligand (sCD40L) in the patients undergoing allogeneic stem cell transplantation: platelet is a major source of serum sCD40L.

CD40 ligand (CD40L) is expressed not only on activated T cells but also on activated platelets. A soluble CD40 ligand (sCD40L) is released from the activated T cells and platelets by ill-defined proteolytic process in vitro. It has been reported that sCD40L is elevated in the serum of patients with systemic lupus erythematosus, unstable angina, essential thrombocythemia, and autoimmune thrombocytopenic purupura. However, source of sCD40L in vivo remains to be elucidated. We investigated the serial sCD40L in the serum in patients undergoing allogeneic stem cell transplantation and compared with the platelets number and soluble IL2R, which is a marker of activated T cells. The value of sCD40L was well correlated with platelet number or thrombopoiesis. In cases of severe graft vs. host disease with markedly increased sIL2R, sCD40L was not increased in vivo. These results indicate that sCD40L in vivo is released mainly from the platelets or in the process of platelet production but not from the activated T cells.

Adolescent↗
PubMed2005

[Experimental study on influence of acupuncture and moxibustion therapy on apoptosis of colonic epithelial cells in rats of ulcerative colitis].

OBJECTIVE: To study the mechanism of acupuncture and moxibustion in adjusting apoptosis of colonic epithelial cells of the rat of ulcerative colitis (UC). METHODS: UC rats were randomly divided into four groups including normal control group (NC), model control group (MC), herbs-partitioned moxibustion group (HPM) and electroacupuncture group (EA). The HPM and EA groups were respectively treated with herbs-partitioned moxibustion and electroacupuncture at "Qihai" (CV 6) and bilateral "Tianshu" (ST 25). Then the colon of the rat was taken and the changes of the tissue structure and the cell apoptosis were observed by electron microscope and flow cytometer respectively. RESULTS: The colon tissue showed histopathological changes, and apoptosis of epithelial cells increased in the model mice of UC as compared with the normal rat. Electroacupuncture and drug-separated moxibustion could significantly decrease the abnormal apoptosis of epithelial cells. CONCLUSION: The adjustment of the abnormal apoptosis of epithelial cells is one of the mechanisms of drug-separated moxibustion and electroacupuncture treating UC.

Acupuncture Points↗