Biomedical subjects

Yuan Zhang

Publications and source records attributed to Yuan Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis.

Bats were recently identified as natural reservoirs of SARS-like coronavirus (SL-CoV) or SARS coronavirus-like virus. These viruses, together with SARS coronaviruses (SARS-CoV) isolated from human and palm civet, form a distinctive cluster within the group 2 coronaviruses of the genus Coronavirus, tentatively named group 2b (G2b). In this study, complete genome sequences of two additional group 2b coronaviruses (G2b-CoVs) were determined from horseshoe bat Rhinolophus ferrumequinum (G2b-CoV Rf1) and Rhinolophus macrotis (G2b-CoV Rm1). The bat G2b-CoV isolates have an identical genome organization and share an overall genome sequence identity of 88-92 % among themselves and between them and the human/civet isolates. The most variable regions are located in the genes encoding nsp3, ORF3a, spike protein and ORF8 when bat and human/civet G2b-CoV isolates are compared. Genetic analysis demonstrated that a diverse G2b-CoV population exists in the bat habitat and has evolved from a common ancestor of SARS-CoV.

Animals↗

PubMed2006

Liver X receptors regulate adrenal cholesterol balance.

Cholesterol is the obligate precursor to adrenal steroids but is cytotoxic at high concentrations. Here, we show the role of the liver X receptors (LXRalpha and LXRbeta) in preventing accumulation of free cholesterol in mouse adrenal glands by controlling expression of genes involved in all aspects of cholesterol utilization, including the steroidogenic acute regulatory protein, StAR, a novel LXR target. Under chronic dietary stress, adrenal glands from Lxralphabeta-/- mice accumulated free cholesterol. In contrast, wild-type animals maintained cholesterol homeostasis through basal expression of genes involved in cholesterol efflux and storage (ABC transporter A1 [ABCA1], apoE, SREBP-1c) while preventing steroidogenic gene (StAR) expression. Upon treatment with an LXR agonist that mimics activation by oxysterols, expression of these target genes was increased. Basally, Lxralphabeta-/- mice exhibited a marked decrease in ABCA1 and a derepression of StAR expression, causing a net decrease in cholesterol efflux and an increase in steroidogenesis. These changes occurred under conditions that prevented the acute stress response and resulted in a phenotype more specific to the loss of LXRalpha, including hypercorticosteronemia, cholesterol ester accumulation, and adrenomegaly. These results imply LXRalpha provides a safety valve to limit free cholesterol levels as a basal protective mechanism in the adrenal gland, where cholesterol is under constant flux.

ATP Binding Cassette Transporter 1↗

PubMed2006

A cerebroprotective dose of intravenous citrate/sorbitol-stabilized dehydroascorbic acid is correlated with increased cerebral ascorbic acid and inhibited lipid peroxidation after murine reperfused stroke.

OBJECTIVE: Oxidative damage has been implicated in the pathogenesis of cerebral ischemia. We previously demonstrated that exogenously supplied dehydroascorbic acid (DHA), an oxidized, blood-brain barrier transportable form of the antioxidant ascorbic acid (AA), improves outcome after experimental stroke. METHODS: To investigate the neuroprotective effect of DHA therapy, we measured cerebral AA levels using a novel assay, quantified markers of lipid peroxidation, and evaluated infarct volume after reperfused stroke in a murine model. All experiments were performed using a new citrate/sorbitol-stabilized DHA formulation to improve the stability of the compound. RESULTS: Intraparenchymal AA levels declined after cerebral ischemia/reperfusion and were repleted in a dose-dependent fashion by postischemic administration of intravenous DHA (P < 0.01). Repletion of these levels was associated with reductions in cerebral malondialdehyde levels (P < 0.05), which were also elevated after reperfused stroke. DHA repletion of interstitial AA levels and reduction in cerebral lipid peroxidation was associated with dose-dependent reductions in infarct volume (P < 0.05). CONCLUSION: Together, these results indicate that an intravenous cerebroprotective dose of citrate/sorbitol-stabilized DHA is correlated with increased brain ascorbate levels and a suppression of excessive oxidative metabolism.

Animals↗

PubMed2006

Transforming growth factor-beta in human diabetic nephropathy: effects of ACE inhibition.

OBJECTIVE: Studies in rodent models have suggested that reduction in renal transforming growth factor (TGF)-beta1 may underlie the renoprotective effects of the renin-angiotensin system (RAS) blockade. However, the role of the RAS blockade in abrogating TGF-beta in human disease is unknown. Accordingly, we sought to examine TGF-beta gene expression and biological activity in human renal biopsies, before and after ACE inhibition. RESEARCH DESIGN AND METHODS: RNA was extracted from renal biopsies taken from participants in the Diabiopsies study, a randomized controlled 2-year trial of 4 mg/day perindopril versus placebo that reported a reduction in proteinuria and cortical matrix expansion in type 2 diabetic nephropathy. Biopsies taken at study entry and at 2 years were obtained in 12 patients (6 placebo and 6 taking perindopril). TGF-beta1 and its receptor mRNA were quantified by real-time PCR, and its biological activity was assessed by examining the activation of its intracellular signaling pathway (phosphorylated Smad2) and the expression TGF-beta-inducible gene H3 (betaig-H3). RESULTS: At baseline, TGF-beta1 expression was similar in both placebo- and perindopril-treated groups and was unchanged over a 2-year period in biopsies of placebo-treated subjects. In contrast, perindopril treatment led to a substantial diminution in TGF-beta1 mRNA (mean 83% reduction, P < 0.05). Phosphorylated Smad2 immunolabeling and betaig-H3 mRNA were similarly reduced with ACE inhibition (P < 0.05) but unchanged in the placebo group. No differences were noted in the gene expression of TGF-beta receptor II in biopsies of either placebo- or perindopril-treated subjects. CONCLUSIONS: This study demonstrates that over a 2-year period, treatment with perindopril in patients with type 2 diabetes and nephropathy leads to a reduction in both renal TGF-beta1 gene expression and its downstream activation.

Adult↗

PubMed2006

Preclinical evaluation of the neuroprotective effect of soluble complement receptor type 1 in a nonhuman primate model of reperfused stroke.

OBJECT: Postischemic cerebral inflammatory injury has been extensively investigated in an effort to develop effective neuroprotective agents. The complement cascade has emerged as an important contributor to postischemic neuronal injury. Soluble complement receptor Type 1 (sCR1), a potent inhibitor of complement activation, has been shown to reduce infarct volume and improve functional outcome after murine stroke. Given numerous high-profile failures to translate promising antiinflammatory strategies from the laboratory to the clinic and given the known species-specificity of the complement cascade, the authors sought to evaluate the neuroprotective effect of sCR1 in a nonhuman primate model of stroke. METHODS: A total of 48 adult male baboons (Papio anubis) were randomly assigned to receive 15 mg/kg of sCR1 or vehicle. The animals were subjected to 75 minutes of middle cerebral artery occlusion/reperfusion. Perioperative blood samples were analyzed for total complement activity by using a CH50 assay. Infarct volume and neurological scores were assessed at the time the animals were killed, and immunohistochemistry was used to determine cerebral drug penetration and C1q deposition. An interim futility analysis led to termination of the trial after study of 12 animals. Total serum complement activity was significantly depressed in the sCR1-treated animals compared with the controls. Immunostaining also demonstrated sCR1 deposition in the ischemic hemispheres of treated animals. Despite these findings, there were no significant differences in infarct volume or neurological score between the sCR1--and vehicle-treated cohorts. CONCLUSIONS: A preischemic bolus infusion of sCR1, the most effective means of administration in mice, was not neuroprotective in a primate model. This study illustrates the utility of a translational primate model of stroke in the assessment of promising antiischemic agents prior to implementation of large-scale clinical trials.

Animals↗

PubMed2006

[Effects and mechanism of total saponins of Psammosilene tunicoids against rheumatoid arthritis].

OBJECTIVE: To observe the antiarthritic effects and the possible mechanism of total saponins of Psammruosilene tunicoids (TSPT) against rheumatoid arthritis (RA). METHOD: After establishing AA rat model, the TSPT'S antiarthritic effects and mechanism against RA were studied through observing the changes of ankle swelling, arthritis index and levels of IL-1beta and TNF-alpha after medication. RESULT: TSPT could effectively inhibits articular swelling, decrease arthritis index and regulate down the content of IL-1beta and TNF-alpha in the inflammatory tissue soak of AA rats. CONCLUSION: TSPT has good antiarthritic effects and the possible mechanism may be related to its down-regulation of IL-1beta and TNF-alpha.

Animals↗

PubMed2006

[Establishment of conditionally immortalized rat cochlear greater epithelial ridge and lesser epithelial ridge cell lines using a retrovirus-mediated gene transfer technique].

OBJECTIVE: To facilitate further investigation of the function of greater epithelial ridge (GER) and lesser epithelial ridge (LER) cells, a greater a lesser epithelial ridge cell immortal line originated from postnatal rat cochleae were established. METHOD: The GER and LER cells were dissected from P1 rats cochleae and infected with SV40-LT antigen using a retrovirus-mediated method. The established cell lines were purified by monoclone technique and identified following morphology observation and immunocytochemical staining. RESULT: The established cell lines had been stably maintained continuously for more than 20 passages and displayed many features similar to epithelial cells. They grew in patches and assumed a polygonal morphology. Immunocytochemical characterization revealed that these cells could be labeled by GER/LER marker (Isletl) and SV40-LT antigen. CONCLUSION: In the present experiment, the GER and LER cell line from postnatal rat cochleae has been successfully established and this cell line may potentially provide an invaluable system for studying hair cell differentiation and regeneration as well as the therapy of sensory deafness caused by auditory hair cells loss.

Animals↗

PubMed2006

[Determination of trace lead in water samples and salt samples by graphite furnace atomic absorption spectrometry after cloud point extraction].

A method was developed for the determination of trace lead in water samples and salt samples by GFAAS after cloud point extraction. The parameters of extraction system such as pH, the concentrations of the extractant and the surfactant, and the time for cloud point extraction were optimized. Under the optimized conditions, the detection limits of lead were 0.000 5 microg x g(-1) for salt, and 0.01 microg x L(-1) for water, respectively. The proposed method was applied to the determination of lead in water samples and salt samples, and satisfactory results were obtained.

Lead↗

PubMed2005

The effect of endogenous formaldehyde on the rat aorta endothelial cells.

Previous studies have demonstrated endogenous formaldehyde (FA) may be involved in endothelial damage, and may be a potential factor of vulnerability of atherosclerosis. However, the mechanism has not been characterized. The present studies examined DNA-protein cross-links (DPC) formation in rat aorta endothelial cells (RAECs) treated with formaldehyde, hydrogen peroxide (H2O2), or formaldehyde with equal molar concentration of H2O2, which is produced with formaldehyde in the body at the same time. Using a K+/SDS precipitation assay for DPC determination, concentration-dependent increases in DPC formation were observed 1.5 h after treatment of RAECs with 0.01-2mM FA, H2O2, or FA with equal molar concentration of H2O2. Time-dependent increases in DPC formation were also observed at 0.5-4 h time point after treatment of RAECs with 0.05 and 0.1mM FA, or 0.1mM FA with H2O2. The DPC levels reduced after treatment with FA and equal molar concentration of H2O2, compared with treatment with FA alone. FA may be less cytotoxic, as FA alone did not affect the cell viability even treating for 4h, until the treatment concentration reached 2mM. However, H2O2, and FA with H2O2 induced significant decreases of cell viability. These studies suggest that FA and H2O2 may injure endothelial cells synergistically, and low concentration of FA (0.05-0.1) may contribute to the endothelial injury in the body during aging.

Animals↗

PubMed2005

Renal expression and localization of the facilitative glucose transporters GLUT1 and GLUT12 in animal models of hypertension and diabetic nephropathy.

Renal tubular glucose reabsorption is mediated by facilitative glucose transporter (GLUT) proteins and energy-dependent sodium glucose luminal transporters. Glucose transport in the diabetic kidney is upregulated and has been implicated in the pathogenesis of progressive diabetic nephropathy. Hyperglycemia, hypertension, and activation of the renin-angiotensin system are believed important in the development of the disease. The present study examines the renal expression of the facilitative glucose transporters GLUT1 and GLUT12 in rat models of diabetic nephropathy. Sprague-Dawley and transgenic (mRen-2)27 rats received either streptozotocin-induced diabetes or vehicle. GLUT12 expression and localization were determined by immunohistochemistry, immunoblotting, in situ hybridization, and confocal immunofluorescence. GLUT1 immunolabeling was detected on the basolateral membrane throughout the nephron. GLUT12 was localized to the distal tubules and collecting ducts. A significant increase in GLUT12 immunolabeling was measured in Ren-2 controls and Ren-2 diabetic animals compared with Sprague-Dawley controls. GLUT12 expression was higher in Ren-2 diabetic compared with Sprague-Dawley diabetic rats. Long-term diabetes resulted in significant increases in GLUT1 levels in the renal proximal tubules and expression was higher in Ren-2 diabetic than Sprague-Dawley diabetic rats. GLUT12 protein was localized to the cytoplasm and to the apical membrane of human and rat distal tubules and collecting ducts. The apical localization of GLUT12 in the distal tubules and collecting ducts suggests that it could contribute to additional glucose reabsorption in the late nephron. Levels of both GLUT1 and GLUT12 are elevated in animal models of hypertension and diabetic nephropathy.

Animals↗

PubMed2005

Homology modeling and substrate binding study of Nudix hydrolase Ndx1 from Thermos thermophilus HB8.

With homology modeling techniques, molecular mechanics, and molecular dynamics methods, a 3D structure model of Ndx1 is created and refined. This model is further assessed by Profile-3D and ProStat, which confirm that the refined model is reliable. With this model, a flexible docking study is performed and the result indicates that Glu46, Arg88, and Glu90 are three important determinant residues in binding, as they have strong hydrogen bonding interactions and electrostatic interactions with Ap6A. In addition, we further find that three residues, Ser38, Leu39 and Glu46, coordinate enzyme-bound Mg2+ ions in complex N-A. The Glu46 is consistent with the experimental results by Iwai et al., and the other four residues mentioned above may also play vital roles in catalysis of Ndx1.

Amino Acid Sequence↗

PubMed2005

[The relationship between the C589T polymorphism of IL-4 gene and cholelithiasis].

OBJECTIVE: To investigate the relationship between IL-4 gene polymorphism and cholelithiasis in Chinese population. METHODS: Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphism of IL-4 gene in 81 cholecystolithiasis, 41 patients with biliary duct stone. RESULTS: There were no significant differences of the IL-4 gene polymorphism genotypes and alleles between 81 cholecystolithiasis patients (CC11.1%, CT34.6%, TT54.3%; C28.4.7%, T71.6%). There were significant differences of the IL-4 gene polymorphism genotypes and alleles between 41 patients with biliary duct stone (CC48.8%, CT36.6%, TT14.6%; C67.1%, T32.9%). CONCLUSIONS: The C589T polymorphism of IL-4 gene was not associated with cholecystolithiasis patients in Chinese, but was related to patients with biliary duct stone in Chinese.

Adult↗

PubMed2005

Homology modeling and docking study of cyclin-dependent kinase (CDK) 10.

In order to understand the mechanisms of ligand binding and the interaction between the ligand and the cyclin-dependent kinase 10 (CDK10), a three-dimensional (3D) model of the CDK10 is generated based on the crystal structure of the cyclin-dependent kinase 2 (CDK2) (PDB code 1AQ1) by using InsightII/Homology module. With the aid of the molecular mechanics and molecular dynamics methods, the last refined model is obtained and is further assessed by PROFILE-3D and PROSTAT, which show that the refined model is reliable. With this model, a flexible docking study is performed and the results indicate that the Lys39 and Asp94 form hydrogen bonds and have strong nonbonding interaction with adenosine 5'-triphosphate (ATP). From the docking studies, we also suggest that the Leu141, Tyr21, and Val24 in CDK10 are three important determinant residues in binding as they have strong nonbonding interaction with ATP. The hydrogen bonding interactions also play an important role for the stability of the complex. Our results may be helpful for further experimental investigations.

Amino Acid Sequence↗

PubMed2005

X-ray diffraction-enhanced imaging of uterine leiomyomas.

BACKGROUND: The purpose of this study was to investigate the microstructures of a uterine leiomyoma using a synchrotron-based imaging technique. MATERIAL/METHODS: The tissues of different regions of a uterine leiomyoma were imaged using X-ray diffraction-enhanced imaging. RESULTS: Compared with optical microscopy and conventional X-ray, X-ray diffraction-enhanced imaging can show not only the surface, but also the internal structure of organs or soft tissues with better contrast. Internal hyaline degeneration and the cavum of liquefied uterine leiomyomas are shown very clearly. Some microstructures, such as the myomatous burble, rupture and conglomeration of muscle fiber, and the cavum resulting from red degeneration, can be displayed in X-ray diffraction-enhanced images. These microstructures can show the developmental progress of necrosis in uterine leiomyomas and indicate their potential canceration. CONCLUSIONS: X-ray diffraction-enhanced imaging can clearly show internal microstructures of uterine leiomyomas, making the complex procedure of doing this with a large number of pathology slices avoidable.

Female↗

PubMed2005

Protein kinase Cbeta inhibition attenuates osteopontin expression, macrophage recruitment, and tubulointerstitial injury in advanced experimental diabetic nephropathy.

Tubulointerstitial macrophage accumulation is an important marker of prognosis that correlates closely with declining renal function in a range of human and experimental diseases, including diabetic nephropathy. These inflammatory cells are rich in the profibrotic growth factor TGF-beta such that their presence in areas of injury is frequently associated with tissue fibrosis. The migration of macrophages occurs in response to the site-specific production of chemokines, with osteopontin closely associated with their trafficking into the tubulointerstitium of the kidney. Although cell culture studies indicate that protein kinase C (PKC) mediates the expression of osteopontin, its role in the in vivo setting is unknown. Accordingly, Ren-2 control and diabetic rats that were treated with or without the specific PKC-beta isoform inhibitor ruboxistaurin (10 mg/kg per d) were examined. After 12 wk, diabetic rats showed increases in osteopontin expression in tubular epithelial cells of the cortex in association with macrophage infiltration, interstitial fibrosis, and activity of TGF-beta as indicated by the expression of its receptor activated protein phospho-Smad2 (P < 0.05 for all parameters). Ruboxistaurin treatment significantly attenuated these parameters (P < 0.05) in diabetic rats without affecting either BP or glycemic control. These findings suggest that osteopontin and macrophage accumulation may play a role in the tubulointerstitial injury in diabetic nephropathy and that inhibition of osteopontin expression may be one of the mechanisms by which inhibition of the beta-isoform of PKC confers a renoprotective effect.

Animals↗

PubMed2005

Homology modeling and PAPS ligand (cofactor) binding study of bovine phenol sulfotransferase.

In order to understand the mechanisms of ligand binding and the interaction between the ligand and the bovine phenol sulfotransferase, (bSULT1A1, EC 2.8.2.1) a three-dimensional (3D) model of the bSULT1A1 is generated based on the crystal structure of the estrogen sulfotransferase (PDB code 1AQU) by using the InsightII/Homology module. With the aid of the molecular mechanics and molecular dynamics methods, the final refined model is obtained and is further assessed by Profile-3D and ProStat, which show that the refined model is reliable. With this model, a flexible docking study is performed and the results indicate that 3'-phosphoadenosine-5'- phosphosulfate (PAPS) is a more preferred ligand than coenzyme A (CoA), and that His108 forms hydrogen bond with PAPS, which is in good agreement with the experimental results. From these docking studies, we also suggest that Phe255, Phe24 and Tyr169 in bSULT1A1 are three important determinant residues in binding as they have strong van-der-Waals contacts with the ligand. The hydrogen-bonding interactions also play an important role for the stability of the complex. Our results may be helpful for further experimental investigations.

Amino Acid Sequence↗

PubMed2005

Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors of osteoclast formation.

Two series of oleanolic acid derivatives were synthesized and their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) induced by 1alpha,25-dihydroxy vitamin D3 was evaluated in a co-culture assay system. The structure-activity relationships, together with electronic structure based on the frontier molecular orbitals, for example, HOMO and LUMO, related to different amino acid substituents were studied. Derivatives with proline or phenylalanine showed a tendency to enhance the inhibitory activity.

Animals↗

PubMed2005

Tranilast attenuates cardiac matrix deposition in experimental diabetes: role of transforming growth factor-beta.

OBJECTIVE: The pathological accumulation of extracellular matrix is a characteristic feature of diabetic cardiomyopathy that is directly related to a loss of function. Tranilast (n-[3,4-anthranilic acid), used for the treatment of fibrotic skin diseases, has also been shown to inhibit transforming growth factor-beta (TGF-beta)-induced matrix production in kidney epithelial cells. METHODS: To investigate the effects of tranilast in the diabetic heart, we examined its effects in cultured cardiac fibroblasts and then assessed its effects in (mRen-2)27 diabetic rats with established disease (8 weeks after streptozotocin). RESULTS: In vitro studies demonstrated a 58% reduction in TGF-beta1-induced 3[H]-hydroxyproline incorporation with tranilast 30 microM (p<0.01). At 16 weeks, diabetes in the Ren-2 rat was associated with increased cardiac fibrosis and evidence of TGF-beta1 activation, as measured by the abundance of phosphorylated Smad2. Despite persistent hyperglycaemia and hypertension, tranilast attenuated cardiac fibrosis by 37% (p<0.05) in association with reduction in phospho-Smad2 (p<0.01). CONCLUSION: These findings indicate that tranilast has antifibrotic actions in the Ren-2 model of experimental diabetic cardiac disease by mechanisms that might attributable to reduced TGF-beta activity.

Animals↗