PubMed Health⌕ Search

Biomedical subjects

Li Zhang

Publications and source records attributed to Li Zhang.

At least 109 records · Page 6Linked to original sources

Mac-1 promotes FcgammaRIIA-dependent cell spreading and migration on immune complexes.

The integrin Mac-1 plays a critical role in Fc receptor (FcR)-mediated antibody-dependent cellular cytotoxicity (ADCC). However, the mechanism by which Mac-1 facilitates the functions of FcgammaRIIA, a major FcR expressed on human leukocytes, is not fully understood. We report here that Mac-1 sustains cell adhesion, enhances cell spreading, and accelerates cell migration on preformed immune complexes (ICs) by directly interacting with FcgammaRIIA but not with the IC substrate. Coupling Mac-1 to FcgammaRIIA allows FcgammaRIIA to reside in the leading front of actin polymerization at the filopodial extension and thus could potentially enhance FcgammaRIIA-mediated cell spreading and migration. The direct interaction between Mac-1 and FcgammaRIIA is demonstrated by co-immunoprecipitation, by cell surface co-localization, and by solid-phase binding assays using recombinant alpha(M)I-domain and soluble FcgammaRIIA. Further mutational analysis identifies the E(253)-R(261) sequence within the alpha(M)I-domain as part of the FcgammaRIIA binding interface within Mac-1. Altogether, these results demonstrate that FcgammaRIIA recognizes Mac-1 via the alpha(M)I-domain but not the lectin domain, a distinct feature from other FcRs, and that Mac-1 binding confers FcgammaRIIA with the ability to prolong cell adhesion as well as to spread and migrate on the ICs, leading to effective cell killing by ADCC.

Antigen-Antibody Complex↗

MRI detects white matter reorganization after neural progenitor cell treatment of stroke.

We evaluated the effects of neural progenitor cell treatment of stroke on white matter reorganization using MRI. Male Wistar rats (n = 26) were subjected to 3 h of middle cerebral artery occlusion and were treated with neural progenitor cells (n = 17) or without treatment (n = 9) and were sacrificed at 5-7 weeks thereafter. MRI measurements revealed that grafted neural progenitor cells selectively migrated towards the ischemic boundary regions. White matter reorganization, confirmed histologically, was coincident with increases of fractional anisotropy (FA, P < 0.01) after stroke in the ischemic recovery regions compared to that in the ischemic core region in both treated and control groups. Immunoreactive staining showed axonal projections emanating from neurons and extruding from the corpus callosum into the ipsilateral striatum bounding the lesion areas after stroke. Fiber tracking (FT) maps derived from diffusion tensor imaging revealed similar orientation patterns to the immunohistological results. Complementary measurements in stroke patients indicated that FT maps exhibit an overall orientation parallel to the lesion boundary. Our data demonstrate that FA and FT identify and characterize cerebral tissue undergoing white matter reorganization after stroke and treatment with neural progenitor cells.

Algorithms↗

An alternative to the hand searching gold standard: validating methodological search filters using relative recall.

BACKGROUND: Search filters or hedges play an important role in evidence-based medicine but their development depends on the availability of a "gold standard"--a reference standard against which to establish the performance of the filter. We demonstrate the feasibility of using relative recall of included studies from multiple systematic reviews to validate methodological search filters as an alternative to validation against a gold standard formed through hand searching. METHODS: We identified 105 Cochrane reviews that used the Highly Sensitive Search Strategy (HSSS), included randomized or quasi-randomized controlled trials, and reported their included studies. We measured the ability of two published and one novel variant of the HSSS to retrieve the MEDLINE-index studies included in these reviews. RESULTS: The systematic reviews were comprehensive in their searches. 72% of included primary studies were indexed in MEDLINE. Relative recall of the three strategies ranged from .98 to .91 across all reviews and more comprehensive strategies showed higher recall. CONCLUSION: An approach using relative recall instead of a hand searching gold standard proved feasible and produced recall figures that were congruent with previously published figures for the HSSS. This technique would permit validation of a methodological filter using a collection of approximately 100 studies of the chosen design drawn from the included studies of multiple systematic reviews that used comprehensive search strategies.

Abstracting and Indexing↗

[Effect of epidermal growth factor signal pathway on integrin alpha5 beta1 in prostate cancer cell line DU145].

OBJECTIVE: To investigate the molecular mechanism of epidermal growth factor (EGF) signal pathway on the expression of integrin alpha5 beta1 in prostate cancer cell line DU145. METHODS: Using flow-cytometry, the effects of EGF and the mitogen-activated protein kinase (MAPK) signal pathway inhibitor PD98059 on the expression of integrin alpha5 and beta1 subunits on DU145 cell surface were analyzed. RT-PCR and Western blot methods were used to examined the expression of mRNA and cell total protein of integrin alpha5 and beta1 subunits. And the metastatic phenotypes in DU145 cell were investigated. RESULTS: The expression levels of integrin alpha5 beta1, which was the receptor for fibronectin, were changed. EGF up-regulated the protein and mRNA expression of beta1 subunit on DU145 cell surface, 231% and 248% (P < 0.01) compared to the control respectively, and it could significantly promote the ability of DU145 cell adhesion to fibronectin and migration. However PD98058, which was the inhibitor of MAPK signal pathway, down-regulated the protein and mRNA expression of beta1 subunit, 60% and 63% (P < 0.01) compared to the control respectively, and it had the contrary function on the adhesion and migration ability of DU145 cell. But both had no effect the expression of alpha5 subunit. CONCLUSIONS: EGF might promote the metastatic ability mainly by up-regulating the expression of beta1 subunit by activating MAPK signal pathway in DU145 cells. Their regulation effects are on the mRNA transcriptional level.

Cell Adhesion↗

Effects of blocking the renin-angiotensin system on expression and translocation of protein kinase C isoforms in the kidney of diabetic rats.

BACKGROUND: High glucose and angiotensin II (Ang II) can activate protein kinase C (PKC) in diabetes mellitus. However, it is not clear which isoform of PKC is activated by glucose or Ang II. Our study focused on the effects of angiotensin blockade, using the angiotensin-converting enzyme inhibitor fosinopril, the Ang II receptor blocker irbesartan and their combination, on the expression and translocation of PKC isoforms alpha and betaII in the renal cortex and medulla in diabetes. METHODS: Hyperglycemia was induced with streptozotocin and diabetic rats were randomized to 4 groups: diabetic control, irbesartan group (40 mg/kg daily), fosinopril group (40 mg/kg daily) and combination group (irbesartan plus fosinopril, 20 mg/kg daily, respectively); age-matched normal rats served as normal control. After 4 weeks, expression and translocation of PKC-alpha and -betaII in the renal cortex and medulla were assessed by immunohistochemistry and Western immunoblotting. RESULTS: The expression of PKC-alpha in the membrane and cytosol fractions from the renal cortex was significantly higher in diabetic rats (276.83 +/- 32.44% in membrane, 149.04 +/- 23.42% in cytosol) than that in normal ones. The expression of PKC-betaII in the renal cortex of diabetic rats decreased significantly in the membrane (50.00 +/- 11.68%, p < 0.05) and remained unchanged in the cytosol (94.51 +/- 11.69%, p > 0.05) compared with normal controls. Treatment with irbesartan, fosinopril and their combination partially corrected the abnormalities mentioned above. For the expression of PKC-alpha and -betaII in the medulla, no difference was detected among the 5 groups. CONCLUSION: The renin-angiotensin system was implicated in the pathogenesis of diabetic nephropathy by regulating the activation of PKC isoforms.

Angiotensin II Type 1 Receptor Blockers↗

Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification.

OBJECTIVES: We evaluated the incremental prognostic information provided by multiple corrected QT (QTc) measurements on serial electrocardiograms (ECGs) in patients with the inherited long QT syndrome (LQTS). BACKGROUND: A baseline QTc of > or =500 ms has been shown to be associated with increased risk of cardiac events among LQTS patients. However, the value of QTc measurements on follow-up ECGs in risk assessment has not been determined. METHODS: The risk of a first LQTS-related cardiac event during adolescence was assessed in 375 patients enrolled in the International LQTS Registry for whom serial follow-up ECGs were recorded before age 10. RESULTS: The mean +/- SD difference between the minimum and maximum QTc values on serial ECGs recorded in study patients was 47 +/- 40 ms. The maximum QTc interval recorded before age 10 was the strongest predictor of cardiac events during adolescence (adjusted hazard ratio [HR] = 2.74; p < 0.001). Other follow-up QTc measures, including the baseline, the mean, and the most recent QTc interval recorded before age 10, were less significant risk factors. After adjusting for the maximum QTc value during follow-up, no significant association remained between the baseline QTc value and the risk of subsequent cardiac events (HR = 1.04; p = 0.91). CONCLUSIONS: In LQTS patients, there is a considerable variability in QTc measures in serial follow-up ECGs. The maximum QTc interval provides incremental prognostic information beyond the baseline measurement. We suggest that risk stratification in LQTS patients should include follow-up ECG data.

Adolescent↗

Correlative studies on uPA mRNA and uPAR mRNA expression with vascular endothelial growth factor, microvessel density, progression and survival time of patients with gastric cancer.

AIM: To investigate the correlations between the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and vascular endothelial growth factor (VEGF) protein and clinicopathologic features, microvessel density (MVD) and survival time. METHODS: In situ hybridization and immuno-histochemistry techniques were used to study the expressions of uPA mRNA, uPAR mRNA, VEGF and CD34 protein in 105 gastric carcinoma specimens. RESULTS: Expressions of uPA mRNA, uPAR mRNA and VEGF protein were observed in 61 (58.1%) cases, 70 (66.7%) cases and 67 (63.8%) cases, respectively. The uPA mRNA and uPAR mRNA positive expression rates in infiltrating-type cases (73.7%, 75.4%), stage III-IV (72.1%, 75.4%), vessel invasion (63.2%, 69.9%), lymphatic metastasis (67.1%, 74.4%) and distant metastasis (88.1%, 85.7%) were significantly higher than those of the expanding-type (chi2 = 15.57, P = 0.001; chi2 = 6.91, P = 0.046), stage I-II (chi2 = 19.22, P = 0.001; chi2 = 16.75, P = 0.001), non-vessel invasion (chi2 = 11.92, P = 0.006; chi2 = 14.15, P = 0.002), non-lymphatic metastasis (chi2 = 28.41, P = 0.001; chi2 = 22.5, P = 0.005) and non-distant metastasis (chi2 = 12.32, P = 0.004; chi2 = 17.42, P = 0.002; chi2 = 11.25, P = 0.012; chi2 = 18.12, P = 0.002). The VEGF positive expression rates in infiltrating-type cases (75.4%), stage III-IV (88.5%), vessel invasion (82.9%), lymphatic metastasis (84.3%) and distant metastasis (95.2%) were significantly higher than those of the expanding-type (chi2 = 9.61, P = 0.021), stage I-II (chi2 = 16.66, P = 0.001), non-vessel invasion (chi2 = 29.38, P = 0.001), non-lymphatic metastasis (chi2 = 18.68, P = 0.005), and non-distant metastasis (chi2 = 22.72, P = 0.007; chi2 = 21.62, P = 0.004). The mean MVD in the specimens positive for the uPA mRNA, uPAR mRNA and VEGF protein was markedly higher than those with negative expression groups. Moreover, a positive relation between MVD and uPA mRNA (rs = 0.199, P = 0.042), uPAR mRNA (rs = 0.278, P = 0.035), and VEGF (rs = 0.398, P = 0.048) expressions was observed. The mean survival time in cases with positive uPA mRNA, uPAR mRNA and VEGF protein expression or MVD value > or = 54.9 was significantly shorter than those in cases with negative expression or MVD value < 54.9. CONCLUSION: uPA and uPAR expressions are correlated with enhanced VEGF-induced tumor angiogenesis and may play a role in invasion and nodal metastasis of gastric carcinoma, thereby serving as prognostic markers of gastric cancer.

Adenocarcinoma↗

Detection of H. pylori antibody profile in serum by protein array.

AIM: To detect multiple H. pylori antibodies in serum samples of individuals who carry H. pylori by protein array. METHODS: Recombinant H. pylori antigens, urease B subunit (UreB), vacuolating toxin A (VacA) and cytotoxin associated gene A protein (CagA), were prepared and immobilized in matrixes on nitrocellulose membrane by robotics to bind the specific immunoglobulin G (IgG) antibodies in serum. Staphylococcus protein A (SPA) labeled by colloid gold was used to integrate the immuno-complex and gave red color signal. The scanner based on charge-coupled device (CCD) could collect the image signal and convert it into digital signal. RESULTS: When human IgG was printed on the membrane in increasing concentrations and incubated with immunogold, a linear dose response curve was obtained and the detection limit for IgG was about 0.025 ng. The cutoff values, which were defined as the mean grey level plus 3 times of standard deviation, were 27.183, 28.546 and 27.402, for anti-UreB IgG, anti-CagA IgG and anti-VacA IgG, respectively, as 400 human serum samples with negative H. pylori antibodies were detected by the protein array. When 180 serum samples from patients in hospital were employed for detection of IgG against UreB, CagA and VacA, the sensitivity of the protein array was 93.4%, 95.4%, 96.0%, and the specificity was 94.8%, 94.4% and 97.5%, respectively, as compared with the results obtained by ELISA. The assay also showed high reproducibility, uniformity and stability, and the results were available within 30 min. CONCLUSION: The protein array is a very practical method for rapid detection of multiple antibodies in serum samples. It is especially useful for large scale epidemiological investigation of the infection of H. pylori.

Antibodies, Bacterial↗

Experimental and clinical study of influence of high-frequency electric surgical knives on healing of abdominal incision.

AIM: To study the influence of high-frequency electric surgical knives on healing of abdominal incision. METHODS: Two hundred and forty white rats were divided into 10(0), 10(2), 10(5), and 10(8) groups and rat models of abdominal operation were induced by using electric surgical knives and common lancets respectively. Then they were respectively given hypodermic injections of normal saline and 0.2 mL quantitative mixture of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa at a concentration of 10(2), 10(5) and 10(8). On the basis of the animal experiment, 220 patients undergoing abdominal operations (above type II) were randomly allocated into one of following three groups: electric knife (EK, 93 cases), electro-coagulation (EC, 55 cases) and control (72 cases). High-frequency electric surgical knives were used to dissect abdominal tissues and electro-coagulation for hemostasis in EK group. Common lancets and electro-coagulation were applied in EC group. Common lancets and tying silk suture were used in the controls. RESULTS: In all the groups except group 10(0), infection rate of incisional wounds made by electric surgical knives were remarkably higher than that with common lancets. Furthermore, there were significant differences in groups 10(2), 10(5), and 10(8) (P<0.05), but not in group 10(0) (P>0.05) between EK and EC groups. Clinical studies showed a delayed wound healing in 16 cases (17.20%) in EK, 11 cases (16.36%) in EC and 2 cases (2.86%) in the control groups. A significant difference between EK and the control groups (chi2 = 8.57, P<0.01), and between EC and the control groups (chi2 = 5.66, P<0.05) was observed, but not between EK and EC (chi2 = 0.017, P>0.05). CONCLUSION: High-frequency electric knives may remarkably delay abdominal incision healing. Its application should be minimized so as to reduce the possibility of postoperative complications.

Adult↗

Mild iodine-magnesium exchange of iodoaromatics bearing a pyrimidine ring with isopropylmagnesium chloride.

[reaction: see text] Iodoaromatics bearing a reactive pyrimidine ring underwent a clean iodine-magnesium exchange with isopropylmagnesium chloride in the presence of bis[2-(N,N-dimethylamino)ethyl] ether to provide the corresponding Grignard reagents. The presence of bis[2-(N,N-dimethylamino)ethyl] ether prevented reduction of the pyrimidine ring and addition by isopropylmagnesium chloride. As a result, the newly formed reactive Grignard reagents were allowed to react with electrophiles in a highly selective manner to afford adducts in excellent yields.

Journal Article↗

Prognostic associations of activated mitogen-activated protein kinase and Akt pathways in glioblastoma.

PURPOSE: Activation of mitogen-activated protein kinase (MAPK) and members of the Akt pathway have been shown to promote cell proliferation, survival, and resistance to radiation. This study was conducted to determine whether any of these markers are associated with survival time and response to radiation in glioblastoma. EXPERIMENTAL DESIGN: The expression of phosphorylated (p-)Akt, mammalian target of rapamycin (p-mTOR), p-p70S6K, and p-MAPK were assessed by immunohistochemical staining in 268 cases of newly diagnosed glioblastoma. YKL-40, a prognostic marker previously examined in these tumors, was also included in the analysis. Expression data were tested for correlations with response to radiation therapy in 131 subtotally resected cases and overall survival (in all cases). Results were validated in an analysis of 60 patients enrolled in clinical trials at a second institution. RESULTS: Elevated p-MAPK expression was most strongly associated with poor response to radiotherapy, a finding corroborated in the validation cohort. For survival, higher expressions of p-mTOR, p-p70S6K, and p-MAPK were associated with worse outcome (all P < 0.03). YKL-40 expression was associated with the expressions of p-MAPK, p-mTOR, and p-p70S6K (all P < 0.02), with a trend toward association with p-Akt expression (P = 0.095). When known clinical variables were added to a multivariate analysis, only age, Karnofsky performance score, and p-MAPK expression emerged as independent prognostic factors. CONCLUSIONS: p-MAPK and activated members of the Akt pathway are markers of outcome in glioblastoma. Elevated expression of p-MAPK is associated with increased radiation resistance and represents an independent prognostic factor in these tumors.

Adipokines↗

Expression of tumor necrosis factor alpha and neuronal apoptosis in the developing rat brain after neonatal stroke.

Increased expression of tumor necrosis factor alpha (TNFalpha) has been shown in adult stroke models. However, its expression and relationship with neuronal apoptosis in neonatal rats with transient middle cerebral artery occlusion (MCAO) have not been clearly elucidated. We studied the expression and distribution of TNFalpha and neuronal apoptosis in a postnatal Day 10 rat MCAO model using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, immunohistochemistry, fluorescence double-labeling, and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) analyses. We found TNFalpha mRNA expression increased at 2h and was maintained at high levels until 24h after reperfusion. TNFalpha protein expression was significantly increased from 4 to 8h (p < 0.01) lasting through 24h (p < 0.05) after reperfusion compared to the sham controls. TNFalpha immunoreactive cells were colocalized to neurons in both the core and the penumbra areas of the ischemic cortex. However, apoptotic cells were mainly distributed in the penumbra area and colocalized to neurons as well as to TNFalpha immunoreactive cells in the ischemic cortex. Our findings suggest that TNFalpha expression increases after neonatal stroke and is associated with neuronal apoptosis after transient focal cerebral ischemia.

Animals↗

The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes.

Given the widespread use of insecticides in the environment, it is important to perform studies evaluating their potential effects on humans. Organophosphate insecticides, such as chlorpyrifos, are being phased out; however, the use of pyrethroids in household pest control is increasing. While chlorpyrifos is relatively well studied, much less is known about the potential neurotoxicity of cyfluthrin and other pyrethroids. To gain insights into the neurotoxicity of cyfluthrin, we compared and evaluated the toxicity profiles of chlorpyrifos and cyfluthrin in primary human fetal astrocytes. We found that at the same concentrations, cyfluthrin exerts as great as, or greater toxic effects on the growth, survival, and proper functioning of human astrocytes. By using microarray gene expression profiling, we systematically identified and compared the potential molecular targets of chlorpyrifos and cyfluthrin, at a genome-wide scale. We found that chlorpyrifos and cyfluthrin affect a similar number of transcripts. These targets include molecular chaperones, signal transducers, transcriptional regulators, transporters, and those involved in behavior and development. Further computational and biochemical analyses show that cyfluthrin and chlorpyrifos upregulate certain targets of the interferon-gamma and insulin-signaling pathways and that they increase the protein levels of activated extracellular signal-regulated kinase 1/2, a key component of insulin signaling; interleukin 6, a key inflammatory mediator; and glial fibrillary acidic protein, a marker of inflammatory astrocyte activation. These results suggest that inflammatory activation of astrocytes might be an important mechanism underlying neurotoxicity of both chlorpyrifos and cyfluthrin.

Apoptosis↗

Imaging cerebral blood flow through the intact rat skull with temporal laser speckle imaging.

We discovered that laser speckle temporal contrast analysis (LSTCA) is able to access the two-dimensional (2D) cerebral blood flow velocity and vessel structure through the intact rat skull. It is demonstrated that LSTCA can significantly suppress the influence of the laser speckle from the stationary structure, such as the skull, and thus reveal the blood flow and morphology of blood vessels through the laser speckle images recorded from the intact rat skull.

Algorithms↗

Human vascular smooth muscle cells express a urate transporter.

An elevated serum uric acid is associated with the development of hypertension and renal disease. Renal regulation of urate excretion is largely controlled by URAT1 (SLC22A12), a member of the organic anion transporter superfamily. This study reports the specific expression of URAT1 on human aortic vascular smooth muscle cells, as assessed by reverse transcription-PCR and Western blot analysis. Expression of URAT1 was localized to the cell membrane. Evidence that the URAT1 transporter was functional was provided by the finding that uptake of 14C-urate was significantly inhibited in the presence of probenecid, an organic anion transporter inhibitor. It is proposed that URAT1 may provide a mechanism by which uric acid enters the human vascular smooth muscle cell, a finding that may be relevant to the role of uric acid in cardiovascular disease.

Aorta↗

Shape-controlled synthesis of ternary chalcogenide ZnIn2S4 and CuIn(S,Se)2 nano-/microstructures via facile solution route.

We demonstrated in this paper the shape-controlled synthesis of ZnIn2S4, CuInS2, and CuInSe2 nano- and microstructures through a facile solution-based route. One-dimensional ZnIn2S4 nanotubes and nanoribbons were synthesized by a solvothermal method with pyridine as the solvent, while ZnIn2S4 solid or hollow microspheres were hydrothermally prepared in the presence of a surfactant such as cetyltrimethylammonium bromide (CTAB) or poly(ethylene glycol) (PEG). The mechanisms related to the phase formation and morphology control of ZnIn2S4 are proposed and discussed. The UV-vis absorption spectra show that the as-prepared nano- and micromaterials have strong absorption in a wide range from UV to visible light and that their band gaps are somewhat relevant to the size and morphology. The photoluminescence measurements of the ZnIn2S4 microspheres at room temperature reveal intense excitation at approximately 575 nm and red emission at approximately 784 nm. Furthermore, CuInS2 and CuInSe2 with different morphologies such as spheres, platelets, rods, and fishbone-like shapes were also obtained by similar hydrothermal and solvothermal synthesis.

Journal Article↗

An interaction involving an arginine residue in the cytoplasmic domain of the 5-HT3A receptor contributes to receptor desensitization mechanism.

A large cytoplasmic domain accounts for approximately one-third of the entire protein of one superfamily of ligand-gated membrane ion channels, which includes nicotinic acetylcholine (nACh), gamma-aminobutyric acid type A (GABA(A)), serotonin type 3 (5-HT3), and glycine receptors. Desensitization is one functional feature shared by these receptors. Because most molecular studies of receptor desensitization have focused on the agonist binding and channel pore domains, relatively little is known about the role of the large cytoplasmic domain (LCD) in this process. To address this issue, we sequentially deleted segments of the LCD of the 5-HT3A receptor and examined the function of the mutant receptors. Deletion of a small segment that contains three amino acid residues (425-427) significantly slowed the desensitization kinetics of the 5-HT3A receptor. Both deletion and point mutation of arginine 427 altered desensitization kinetics in a manner similar to that of the (425-427) deletion without significantly changing the apparent agonist affinity. The extent of receptor desensitization was positively correlated with the polarity of the amino acid residue at 427: the desensitization accelerates with increasing polarity. Whereas the R427L mutation produced the slowest desensitization, it did not significantly alter single channel conductance of 5-HT3A receptor. Thus, the arginine 427 residue in the LCD contributes to 5-HT3A receptor desensitization, possibly through forming an electrostatic interaction with its neighboring residues. Because the polarity of the amino acid residue at 427 is highly conserved, such a desensitization mechanism may occur in other members of the Cys-loop family of ligand-gated ion channels.

Amino Acids↗