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Biomedical subjects

Ying Li

Publications and source records attributed to Ying Li.

At least 55 records · Page 3Linked to original sources
PubMed2006

Synthesis and immunosuppressive activity of new artemisinin derivatives. Part 2: 2-[12(beta or alpha)-dihydroartemisinoxymethyl(or 1'-ethyl)]phenoxyl propionic acids and esters.

Another series of novel dihydroartemisinin derivatives were synthesized and assessed for their cytotoxicity of lymphocyte, inhibitory activity on mitogen-induced spleen lymphocyte proliferation in vitro. Some of the compounds exhibited inhibitory effects on ConA-induced T cell and LPS-induced B cell proliferation comparable to or more potent than parent artemisinin.

Artemisinins↗
PubMed2006

Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist.

Women with mutations in the breast cancer susceptibility gene BRCA1 are predisposed to breast and ovarian cancers. Why the BRCA1 protein suppresses tumor development specifically in ovarian hormone-sensitive tissues remains unclear. We demonstrate that mammary glands of nulliparous Brca1/p53-deficient mice accumulate lateral branches and undergo extensive alveologenesis, a phenotype that occurs only during pregnancy in wild-type mice. Progesterone receptors, but not estrogen receptors, are overexpressed in the mutant mammary epithelial cells because of a defect in their degradation by the proteasome pathway. Treatment of Brca1/p53-deficient mice with the progesterone antagonist mifepristone (RU 486) prevented mammary tumorigenesis. These findings reveal a tissue-specific function for the BRCA1 protein and raise the possibility that antiprogesterone treatment may be useful for breast cancer prevention in individuals with BRCA1 mutations.

Animals↗
PubMed2006

Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor.

The conventional protein kinase C isoform, PKCII, is a signaling kinase activated during the hyperglycemic state and has been associated with the development of microvascular abnormalities associated with diabetes. PKCII, therefore, has been identified as a therapeutic target where inhibitors of its kinase activity are being pursued for treatment of microvascular-related diabetic complications. In this report, we describe the crystal structure of the catalytic domain of PKCbetaII complexed with an inhibitor at 2.6 A resolution. The kinase domain of PKCbetaII was cleaved and purified from full-length PKCbetaII expressed in baculovirus-infected insect cells. The overall kinase domain structure follows the classical bilobal fold and is in its fully activated conformation with three well-defined phosphorylated residues: Thr-500, Thr-641, and Ser-660. Different from the crystal structures of nonconventional PKC isoforms, the C-terminus of the PKCbetaII catalytic domain is almost fully ordered and features a novel alpha helix in the turn motif. An ATP-competitive inhibitor, 2-methyl-1H-indol-3-yl-BIM-1, was crystallized with the PKCbetaII catalytic domain as a dimer of two enzyme-inhibitor complexes. The bound inhibitor adopts a nonplanar conformation in the ATP-binding site, with the kinase domain taking on an intermediate, open conformation. This PKCbetaII-inhibitor complex represents the first structural description of any conventional PKC kinase domain. Given the pathogenic role of PKCbetaII in the development of diabetic complications, this structure can serve as a template for the rational design of inhibitors as potential therapeutic agents.

Amino Acid Sequence↗
PubMed2006

Interaction of rhein with human serum albumin investigation by optical spectroscopic technique and modeling studies.

The binding of rhein with human serum albumin (HSA) has been studied in detail by spectroscopic method including circular dichroism (CD), Fourier transformation infrared spectra (FT-IR), fluorescence spectra. The binding parameters for the reaction have been calculated according to Scatchard equation at different temperatures. The plots indicated that the binding of HSA to rhein at 303, 310 and 318 K is characterized by one binding site with the affinity constant K at (4.93+/-0.16)x10(5), (4.02+/-0.16)x10(5) and (2.69+/-0.16)x10(5) M-1, respectively. The secondary structure compositions of free HSA and its rhein complexes were estimated by the FT-IR spectra. FT-IR and curve-fitted results of amide I band are in good agreement with the analyses of CD spectra. Molecular Modeling method was used to calculate the interaction modes between the drug and HSA.

Anthraquinones↗
PubMed2006

Aging in the atherosclerosis milieu may accelerate the consumption of bone marrow endothelial progenitor cells.

OBJECTIVE: We have demonstrated that bone marrow cells from young and wild-type (WT), but not old apoE-/-, mice are capable of preventing atherosclerosis. This study was performed to elucidate the numerical and functional changes underlying the efficacy difference between young and old bone marrow. METHODS AND RESULTS: CD34+/VEGFR2+ conventional endothelial progenitor cells and lin-/cKit+/Sca-1+ hematopoietic stem cells did not differ numerically or functionally between young and old apoE-/- bone marrow. Fluorescence-activated cell sorter analysis, however, showed that a group of cells (simple little cells or SLCs), characteristically located in the lower left quadrant of forward scatter/side scatter flow cytometric plot, were markedly decreased in old WT and apoE-/- marrow, but abundantly present in young WT and apoE-/- bone marrow. The SLC fraction was mainly composed of lin-/cKit-/Sca-1- cells. In vitro differentiation assay demonstrated substantially more efficient endothelial differentiation of lin-/cKit-/Sca-1- SLCs than other bone marrow fractions at a single cell level and en masse. Furthermore, old lin-/cKit-/Sca-1- SLCs had a trend of decreased endothelial differentiation capability. CONCLUSIONS: Lin-/cKit-/Sca-1- SLCs may represent a previously unrecognized cell population, enriched for endothelial progenitors. The identification of these cells may help improve the efficacy of cell therapy.

Animals↗
PubMed2006

Estimation of 10-year risk of fatal and nonfatal ischemic cardiovascular diseases in Chinese adults.

BACKGROUND: Stroke is much more prevalent than coronary heart disease in China; thus, any risk prediction model only for coronary heart disease may not be appropriate in application. Our objective is to develop a cardiovascular risk prediction model appropriate for the Chinese population. METHODS AND RESULTS: Cox proportional hazards regression was used to develop sex-specific optimal 10-year risk prediction models for ischemic cardiovascular disease (ICVD; including ischemic stroke and coronary events) from 17 years of follow-up data from the USA-PRC Collaborative Study of Cardiovascular Epidemiology cohort, in which 9903 participants were followed up every 2 years until 2000, and 371 ICVD events (266 strokes and 105 coronary heart disease events) occurred. The models showed ICVD was positively related to age, systolic blood pressure, serum total cholesterol, body mass index, current smoking status, and diabetes mellitus in both men and women. When the models were applied to the 17,329 participants in the China Multicenter Collaborative Study of Cardiovascular Epidemiology cohort, the areas under the receiver operating characteristic curve were 0.796+/-0.036 for men and 0.791+/-0.036 for women. The simplified point score model resulted in similar c statistics. Comparison of the observed with the estimated incidence of ICVD at different risk levels showed satisfactory precision. Meanwhile, application of recalibrated Framingham models significantly overestimated the coronary heart disease risk in both men (by approximately 97%) and women (by approximately 228%). CONCLUSIONS: The Cox regression prediction models and simplified point score model have satisfying predictive capability for estimating the 10-year integrated cardiovascular risk in Chinese, in whom stroke is the predominant cardiovascular disease.

Adult↗
PubMed2006

Comparison of various kinds of bone marrow stem cells for the repair of infarcted myocardium: single clonally purified non-hematopoietic mesenchymal stem cells serve as a superior source.

A variety of adult stem cells have been used to transplant into the infarcted (MI) heart, however, comparative studies are lacking to show more suitable source of cells for transplantation. We have identified a single non-hematopoietic mesenchymal stem cell subpopulation (snMSCs) isolated from human bone marrow and clonally purified, that over 99% of them expressed MSC marker proteins and cardiomyocyte marker proteins when induction in vitro. We also compared the effects of the snMSCs with unpurified MSC (uMSCs), mononuclear cells (BMMNCs), or peripheral blood mononuclear cells (PBMNCs) on myocardial repair after induction of MI in rats. Ninety days later, we observed a better cardiac function assessed by ejection fraction, fraction of shortening and lung wet/dry weight ratios, less remodeling of left ventricle (LV), lower collagen density in the LV, and more vessels in the ischemic wall in the snMSCs transplantation group than in other cell-transplanted groups. Furthermore, the transplanted cells expressing cardiomyocyte specific proteins or vascular endothelial cell marker proteins were more in the snMSCs group than in other ones. We conclude that transplantation with single clonally purified MSCs seems to be more beneficial to the cardiac repair than with other stem cells after MI.

Adult↗
PubMed2006

Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice.

Restoration of local blood supply in the post-ischemic brain plays a critical role in tissue repair and functional recovery. The present investigation explored beneficial effects of recombinant human erythropoietin (rhEPO) on vascular endothelial cell survival, angiogenesis, and restoration of local cerebral blood flow (LCBF) after permanent focal cerebral ischemia in adult mice. Saline or rhEPO (5,000 U/kg, intraperitoneal) was administered 30 mins before ischemia and once daily after ischemic stroke. Immunohistochemistry showed an enhancing effect of rhEPO on expression of EPO receptor (EPOR) of endothelial cells in the penumbra region 3 to 21 days after the ischemic insult. The treatment with rhEPO decreased ischemia-induced cell death and infarct volume 3 days after stroke. Specifically, rhEPO reduced the number of terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling- and caspase-3-positive endothelial cells in the penumbra region. Colocalization of the vessel marker glucose transporter-1 (Glut-1) and cell proliferation marker 5-bromo-2'-deoxyuridine indicated enhanced angiogenic activity in rhEPO-treated mice 7 to 21 days after stroke. Western blot showed upregulation of the expression of angiogenic factors Tie-2, Angiopoietin-2, and vascular endothelial growth factor in rhEPO-treated animals. Local cerebral blood flow was measured by laser scanning imaging 3 to 21 days after stroke. At 14 days, LCBF in the penumbra was recovered to preischemia levels in rhEPO-treated mice but not in control mice. Our data suggest that rhEPO treatment upregulates the EPOR level in vascular endothelial cells, confers neurovascular protection, and enhances angiogenesis. We further show a promoting effect of rhEPO on LCBF recovery in the ischemic brain. These rhEPO-induced effects may contribute to therapeutic benefits in the treatment of ischemic stroke.

Animals↗
PubMed2006

[Multi-slice computed tomography of myocardial bridge and mural coronary artery and clinical significance thereof].

OBJECTIVE: To investigate the diagnosis of myocardial bridge and mural coronary artery (MB-MCA) with multi-slice computed tomography (MSCT) and clinical significance thereof. METHODS: 900 patients suspected as with coronary artery disease (CHD) underwent 64-slice computed tomography performed by 3 radiologists independently. When consistency was obtained among the independent interpretations of the tomogram among them the diagnosis of MB-MCA could be confirmed. The length of MCA and thickness of MB were measured, and the situation of the nearby arteries were observed and recorded. Based on the above mentioned 3 items the reference scoring criteria were established. RESULTS: 180 sites of MB-NCA were found in 167 (18.56%) of the 900 patients, 112 males and 55 females, aged 54.46 (33 - 84). 167 of the 180 sites of MB-MCA were located on the LAD (92.7%). MCA could be covered by MB in a form of semi-circularity (63.89%, 115/180) or circularity (36.11%, 65/180) The length of MCA was 18.7 mm +/- 10.2 mm, and the thickness of MB was 1.7 mm +/- 1.2 mm. 70% of the arteries proximal and/or distal to the MB-MCA were tortuous. Length of MCA < 10 mm, half-surrounding of MB, and smoothness of the proximal and distant vessels were scored as 1; length of MCA of 10 approximately 20 mm, thickness of MB < 1 mm, and tortuousness of the unilateral proximal or distant vessel were scored as 2; and length of MCA > 20 mm, thickness of MB > 1 mm, and tortuousness of the bilateral proximal and distant vessels were scored as 3. Coronary atherosclerosis was found in 88 of the 167 patients (52.69%). No significant correlation was found between coronary atherosclerosis and MB-MCA grade (u = 1.234, P > 0.05). CONCLUSION: Sixty-four-slice CT can be used to confirm the presence of MB = MCA and the morphology of coronary artery with MB-MCA. Coronary atherosclerosis is not significantly correlated with MB-MCA grade.

Adult↗
PubMed2006

Investigation on the sonocatalytic degradation of acid red B in the presence of nanometer TiO2 catalysts and comparison of catalytic activities of anatase and rutile TiO2 powders.

Here, the nanometer anatase and rutile titanium dioxide (TiO(2)) powders were introduced to act as the sonocatalysts during the ultrasonic degradation of azo dye-acid red B which was chosen as model compound. The ultrasound of low power was used as an irradiation source to induce TiO(2) particles performing catalytic activity. It was found that the processes of sonocatalytic degradation were different between nanometer anatase TiO(2) and nanometer rutile TiO(2). For nanometer anatase TiO(2) catalyst, the acid red B was mainly oxidated by the holes on the surface of nanometer anatase TiO(2) particles, so that the decolorization and degradation happened at the same time. For the nanometer rutile TiO(2) catalyst, the acid red B was mainly oxidated by the *OH radicals from the ultrasonic cavitation, so that the decolorization of azo bond takes place primarily, and then the degradation of naphthyl ring does. The intermediates of acid red B in the presence of nanometer anatase and rutile TiO(2) powders have been monitored by UV-vis spectra and high performance liquid chromatography (HPLC), respectively. All experiments indicated that the degradation effect of acid red B in the presence of nanometer anatase TiO(2) powder was obviously better than that in the presence of nanometer rutile TiO(2) powder. Hence, the method of sonocatalytic degradation for organic pollutants in the presence of nanometer anatase TiO(2) powder is expected to be promising as an advisable choice for the treatment of organic wastewaters in future.

Azo Compounds↗
PubMed2006

Calcium influx through If channels in rat ventricular myocytes.

The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, or cardiac (I(f))/neuronal (I(h)) time- and voltage-dependent inward cation current channels, are conventionally considered as monovalent-selective channels. Recently we discovered that calcium ions can permeate through HCN4 and I(h) channels in neurons. This raises the possibility of Ca(2+) permeation in I(f), the I(h) counterpart in cardiac myocytes, because of their structural homology. We performed simultaneous measurement of fura-2 Ca(2+) signals and whole cell currents produced by HCN2 and HCN4 channels (the 2 cardiac isoforms present in ventricles) expressed in HEK293 cells and by I(f) in rat ventricular myocytes. We observed Ca(2+) influx when HCN/I(f) channels were activated. Ca(2+) influx was increased with stronger hyperpolarization or longer pulse duration. Cesium, an I(f) channel blocker, inhibited I(f) and Ca(2+) influx at the same time. Quantitative analysis revealed that Ca(2+) flux contributed to approximately 0.5% of current produced by the HCN2 channel or I(f). The associated increase in Ca(2+) influx was also observed in spontaneously hypertensive rat (SHR) myocytes in which I(f) current density is higher than that of normotensive rat ventricle. In the absence of EGTA (a Ca(2+) chelator), preactivation of I(f) channels significantly reduced the action potential duration, and the effect was blocked by another selective I(f) channel blocker, ZD-7288. In the presence of EGTA, however, preactivation of I(f) channels had no effects on action potential duration. Our data extend our previous discovery of Ca(2+) influx in I(h) channels in neurons to I(f) channels in cardiac myocytes.

Animals↗
PubMed2006

Toxoplasma gondii: expression and characterization of a recombinant protein containing SAG1 and GRA2 in Pichia pastoris.

Toxoplasma gondii is an obligate intracellular protozoan which infects most species of warm-blooded animals and causes toxoplasmosis. Previous immunological and immunization studies have demonstrated the potential role of T. gondii antigens SAG1 and GRA2 as a vaccine candidate. In the present study, we have cloned, expressed, and purified a recombinant protein SAG1-GRA2 in Pichia pastoris. Results showed that P. pastoris was a robust system producing a large amount of highly purified and biological activity protein. BALB/c mice immunized with SAG1-GRA2 elicited stronger humoral and cellular responses in comparison to control groups. This immunization resulted in an enhanced Th1 immune response as measured by IgG2a antibody production and increased splenocyte IFN-gamma production, whereas no IL-4 was detected. After a lethal challenge with the highly virulent T. gondii RH strain, a prolonged survival time in SAG1-GRA2-immunized mice was observed in comparison to control groups. Our data demonstrate that SAG1-GRA2 triggered a protective response against toxoplasmosis. Therefore, SAG1-GRA2 protein might be a good candidate for the further development of a multiantigenic vaccine.

Animals↗
PubMed2006

Role of moisture in adsorption, photocatalytic oxidation, and reemission of elemental mercury on a SiO2-TiO2 nanocomposite.

A novel silica-titania (SiO2-TiO2) nanocomposite has been developed to effectively capture elemental mercury (Hg0) under UV irradiation. Moisture has been reported to have an important impact on this nanocomposite's performance. In this work, the role of moisture on Hg0 removal and reemission as well as the corresponding mechanisms was investigated. Hg0 removal experiments were carried out in a fixed-bed reactor at 65 degrees C using air as the carrier gas. Without UV irradiation, Hg0 adsorption was found to be insignificant, but it could be enhanced by the photocatalytic oxidation product, mercuric oxide (HgO), possibly due to the high affinity between HgO and Hg0. Under dry conditions 95% of Hg0 can be removed; however, increased humidity levels remarkably suppress both Hg0 adsorption and photocatalytic oxidation. Introducing water vapor can also result in significant reemission of captured Hg0 from the nanocomposite, which may be ascribed to the repellant effect of water vapor adsorbed on the superhydrophilic TiO2 surface. Exposure to UV light was found either to prohibit Hg0 reemission when photocatalytic oxidation of reemitted Hg0 prevailed or to promote Hg0 reemission when photocatalytic reduction of HgO to Hg0 dominated later on. The results indicate that minimization of Hg0 reemission can be achieved by appropriate application of UV irradiation.

Adsorption↗
PubMed2006

Overexpression of the gene for transmembrane 4 superfamily member 4 accelerates liver damage in rats treated with CCl4.

BACKGROUND/AIMS: Transmembrane 4 superfamily member 4 (TM4SF4) is up-regulated in regenerating liver after partial hepatectomy in rats, but the in vivo functions of this protein are still largely unknown. Therefore, we investigated the role of TM4SF4 during liver injury. METHODS: Expression of TM4SF4 was analyzed by RT-PCR and Western blotting in normal and CCl4-injured rats. Overexpression or reduced expression of TM4SF4 in the liver was achieved by injection of sense or antisense TM4SF4 expression plasmids. Assessment of liver injury (histology, serum ALT and AST levels), apoptosis by TUNEL assay were performed. Expression of injury-related genes was analyzed by quantitative real-time PCR. RESULTS: Overexpression of TM4SF4 in rats after CCl4 treatment showed extensive liver damage and increased levels of serum ALT and AST. Decreased TM4SF4 gene expression showed minimal liver necrosis and depressed ALT and AST levels. Increased expression of TM4SF4 affected the expression levels of growth factors and receptors, such as TNF-alpha, TNFR1 and c-met. Furthermore, pro-apoptotic and anti-apoptotic gene expression was altered after TM4SF4 administration. CONCLUSIONS: Rat TM4SF4 is overexpressed in acutely injured liver induced by CCl4 and plays a crucial role in accelerating liver injury, which may be mediated by the TNF-alpha and HGF/c-met signaling pathways.

Alanine Transaminase↗
PubMed2006

Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.

The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method of assessing GFR in patients with chronic kidney disease (CKD). However, previous research indicated that modification of these equations is necessary for application in Chinese patients with CKD. The objective of this study was to modify MDRD equations on the basis of the data from the Chinese CKD population and compare the diagnostic performance of the modified MDRD equations with that of the original MDRD equations across CKD stages in a multicenter, cross-sectional study of GFR estimation from plasma creatinine, demographic data, and clinical characteristics. A total of 684 adult patients with CKD, from nine geographic regions of China were selected. A random sample of 454 of these patients were included in the training sample set, and the remaining 230 patients were included in the testing sample set. With the use of the dual plasma sampling (99m)Tc-DTPA plasma clearance method as a reference for GFR measurement, the original MDRD equations were modified by two methods: First, by adding a racial factor for Chinese in the original MDRD equations, and, second, by applying multiple linear regression to the training sample and modifying the coefficient that is associated with each variable in the original MDRD equations and then validating in the testing sample and comparing it with the original MDRD equations. All modified MDRD equations showed significant performance improvement in bias, precision, and accuracy compared with the original MDRD equations, and the percentage of estimated GFR that did not deviate >30% from the reference GFR was >75%. The modified MDRD equations that were based on the Chinese patients with CKD offered significant advantages in different CKD stages and could be applied in clinical practice, at least in Chinese patients with CKD.

Algorithms↗
PubMed2006

Heme utilization in Campylobacter jejuni.

A putative iron- and Fur-regulated hemin uptake gene cluster, composed of the transport genes chuABCD and a putative heme oxygenase gene (Cj1613c), has been identified in Campylobacter jejuni NCTC 11168. Mutation of chuA or Cj1613c leads to an inability to grow in the presence of hemin or hemoglobin as a sole source of iron. Mutation of chuB, -C, or -D only partially attenuates growth where hemin is the sole iron source, suggesting that an additional inner membrane (IM) ABC (ATP-binding cassette) transport system(s) for heme is present in C. jejuni. Genotyping experiments revealed that Cj1613c is highly conserved in 32 clinical isolates. One strain did not possess chuC, though it was still capable of using hemin/hemoglobin as a sole iron source, supporting the hypothesis that additional IM transport genes are present. In two other strains, sequence variations within the gene cluster were apparent and may account for an observed negative heme utilization phenotype. Analysis of promoter activity within the Cj1613c-chuA intergenic spacer region revealed chuABCD and Cj1613c are expressed from separate iron-repressed promoters and that this region also specifically binds purified recombinant Fur(Cj) in gel retardation studies. Absorbance spectroscopy of purified recombinant His(6)-Cj1613c revealed a 1:1 heme:His(6)-Cj1613c binding ratio. The complex was oxidatively degraded in the presence of ascorbic acid as the electron donor, indicating that the Cj1613c gene product functions as a heme oxygenase. In conclusion, we confirm the involvement of Cj1613c and ChuABCD in heme/hemoglobin utilization in C. jejuni.

Bacterial Proteins↗