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Biomedical subjects

Jing Hua

Publications and source records attributed to Jing Hua.

15 recordsLinked to original sources
PubMed2005

Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling.

BACKGROUND: Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. METHODS AND RESULTS: MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a (111)In-labeled MMP-targeted radiotracer ((111)In-RP782) and negative control compound ((111)In-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of (111)In-RP782 was demonstrated within the MI by microautoradiography. A 334+/-44% increase (P<0.001 versus Ctrl) in relative retention of (111)In-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro-single-photon emission computed tomography/CT imaging studies with an analogous 99mTc-labeled MMP-targeted radiotracer (99mTc-RP805) and 201Tl demonstrated favorable biodistribution and clearance kinetics of 99mTc-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased 201Tl perfusion. Gamma well counting yielded a similar approximately 300% increase in relative myocardial retention of 99mTc-RP805 in MI regions (Ctrl, 102+/-9%; 1 week, 351+/-77%; 2 weeks, 291+/-45%; 3 weeks, 292+/-41%; P<0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased approximately 5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. CONCLUSIONS: This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling.

Animals↗
PubMed2005

Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at alphavbeta3 integrin after murine hindlimb ischemia.

BACKGROUND: Noninvasive imaging strategies play a critical role in assessment of the efficacy of angiogenesis therapies. The alpha(v)beta3 integrin is activated in angiogenic vessels and represents a potential target for noninvasive imaging of angiogenesis. METHODS AND RESULTS: We evaluated a 99mTc-labeled peptide (NC100692) targeted at alpha(v)beta3 integrin for imaging in an established murine model of angiogenesis induced by hindlimb ischemia. Control mice (n=9) or mice with surgical right femoral artery occlusion (n=29) were injected with NC100692 (1.5+/-0.2 mCi IV) at different times after femoral occlusion (1, 3, 7, and 14 days) for in vivo pinhole planar gamma camera imaging. Tissue from hindlimb proximal and distal to occlusion was excised for gamma well counting and for immunostaining. On in vivo pinhole images, increased focal NC100692 activity was seen distal to the occlusion at days 3 and 7. This increase in relative NC100692 activity was confirmed by gamma well counting. Lectin staining confirmed increased angiogenesis in the ischemic hindlimb at these time points. A fluorescent analogue of NC100692 was used to confirm specificity and localization of the targeted tracer in cultured endothelial cells. In addition, endothelial cell specificity was confirmed on tissue sections with the use of dual immunofluorescent staining of endothelium and the fluorescent analogue targeted at the alpha(v)beta3 integrin. CONCLUSIONS: A 99mTc-labeled peptide (NC100692) targeted at alpha(v)beta3 integrin selectively localized to endothelial cells in regions of increased angiogenesis and could be used for noninvasive serial "hot spot" imaging of angiogenesis. This targeted radiotracer imaging approach is a major advance in tracking therapeutic myocardial angiogenesis and has an important clinical potential.

Animals↗
PubMed2005

CD14 expression on Kupffer cells during the course of carbon tetrachloride-mediated liver injury.

OBJECTIVE: To investigate the expression of CD14 on Kupffer cells during the course of carbon tetrachloride (CCl(4))-mediated liver injury and its role in the activation of Kupffer cells. METHODS: Rats were administered CCl(4) twice weekly for up to 8 weeks. Kupffer cells were isolated from normal and CCl(4)-treated rats by the combined 'collagenase-pronase' perfusion method, discontinuous density gradient centrifugation. On the day after isolation, the cells were incubated with RPMI-1640 containing varying doses of lipopolysaccharide (LPS) for 6 h. Supernatants were then collected for measuring the concentration of tumor necrosis factor-alpha (TNF-alpha) by enzyme-linked immunosorbent assay (ELISA). The expression of CD14 mRNA on Kupffer cells were determined by RT-PCR. The plasma concentrations of endotoxin were determined by chromogenic substrate Limulus amebocyte lysate assay. RESULTS: Basic TNF-alpha production of Kupffer cells isolated from CCl(4)-treated rats at 4 and 6 weeks was significantly higher than that of normal (P < 0.05). Following LPS stimulation the production of TNF-alpha was markedly increased in Kupffer cells from the 2-, 4- and 6-week treatment groups (P < 0.05). Moreover, LPS-induced TNF-alpha production was dose-dependent. CD14 mRNA expression on Kupffer cells isolated from CCl(4)-treated rats was elevated following 2 weeks of CCl(4) administration and the maximum elevation occurred at 6 weeks. Gene expression was decreased in Kupffer cells after 8 weeks of CCl(4) treatment. CCl(4) administration elicited extensive changes in liver morphology, including steatosis, inflammation and necrosis. The plasma concentrations of endotoxin of CCl(4)-treated rats were increased during the time of liver injury. CONCLUSION: Up-regulation of CD14 expression in Kupffer cells during CCl(4)-mediated chronic liver injury indicates cell activation and that they are more sensitive to LPS stimulation. Kupffer cells are critical effector cells in the early stage of liver injury.

Animals↗
PubMed2004

[Interferon-inducible genes lymphocyte antigen 6 complex E and tetratricopeptide repeats 1 are correlated with clinical features of patients with systemic lupus erythematosus].

OBJECTIVE: To investigate the expression levels of lymphocyte antigen 6 complex, locus E (LY6E) and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) genes in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), and to evaluate the relations between these gene expression levels and disease activity. METHODS: The clinical data of 144 SLE patients, 27 non-SLE patients with rheumatic diseases, and 59 normal controls were collected. The SLE patients were further divided into 2 subgroups: active SLE group (n = 87) and non-active SLE group (n = 57) according to SLEDAI scores. Specimens of peripheral blood were drawn; total RNA was extracted and transcribed into cDNA. Sybr green dye based real-time quantitative PCR method was used to compare the expression levels (indicated as-DeltaDeltaCT value) of LY6E and IFIT1 in patients with SLE and those in the controls. RESULTS: (1) The-DeltaDeltaCT value of LY6E expression level of the SLE patients was 5.4760 +/- 1.9806, significantly higher than those of the non-SLE patients (3.4323 +/- 1.7456) and normal controls (4.5198 +/- 1.6359, both P = 0.001). (2) The-DeltaDeltaCT value of LY6E and IFIT1 mRNA expression of the active SLE patients were 6.1960 +/- 1.7729 and 6.4997 +/- 2.6297 respectively, significantly higher than those observed in the inactive SLE patients (4.3770 +/- 1.7764 and 4.1327 +/- 2.6044 respectively, both P = 0.000). The-DeltaDeltaCT values of LY6E and IFIT1 mRNA of the SLE patients were correlated with the SLEDAI scores, and with the numbers of matched criteria used in the diagnosis of SLE (P < 0.001). CONCLUSION: As IFN-induced genes, elevated expression of LY6E mRNA is specific to diagnosis of SLE. The real time expression levels of LY6E and IFIT1 genes are associated with SLE disease activity. To inhibit the expression of LY6E and IFIT1 may become a novel therapeutic approach for SLE.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Arteriogenesis proceeds via ICAM-1/Mac-1- mediated mechanisms.

Monocyte adhesion to shear stress-activated endothelium stands as an important initial step during arteriogenesis (collateral artery growth). Using multiple approaches, we tested the hypothesis that monocyte adhesion via intercellular adhesion molecule-1 (ICAM-1) and selectin interactions is essential for adaptive arteriogenesis. Forty-eight New Zealand White rabbits received either solvent, monocyte chemoattractant protein-1 (MCP-1) alone, MCP-1 plus ICAM-mab, or MCP-1 plus an IgG2a isotype control via osmotic minipumps. After 7 days, collateral conductance was evaluated: solvent 4.01 (mL/min per 100 mm Hg), MCP-1 plus ICAM-mab 8.04 (versus solvent P=NS), and MCP-1 alone 33.11 (versus solvent P<0.05). Furthermore, the right femoral arteries of ICAM-1-/-, Mac-1-/- and mice having defective selectin interactions (FT4/7-/-) as well as their corresponding controls were ligated. One week later, perfusion ratios were determined by the use of fluorescent microspheres. FT4/7-/- mice did not show any significant difference in perfusion restoration whereas ICAM-1-/- and Mac-1-/- mice had a significant reduction in arteriogenesis as compared with matching controls (FT4/7-WT 37+/-9%, FT4/7-/- 32+/-3%, P=0.31; C57BL/6J 59+/-9%, ICAM-1-/- 36+/-8%, P<0.05; Mac-1-/- 42+/-3%, P<0.05). ICAM-1/Mac-1-mediated monocyte adhesion to the endothelium of collateral arteries is an essential step for arteriogenesis, whereas this process can proceed via selectin interaction independent mechanisms. Furthermore, in vivo treatment with monoclonal antibodies against ICAM-1 totally abolishes the stimulatory effect of MCP-1 on collateral artery growth, suggesting that the mechanism of the MCP-1-induced arteriogenesis proceeds via the localization of monocytes rather than the action of the MCP-1 molecule itself.

Animals↗
PubMed2004

Root border cell development is a temperature-insensitive and Al-sensitive process in barley.

In vivo and in vitro experiments showed that border cell (BC) survival was dependent on root tip mucigel in barley (Hordeum vulgare L. cv. Hang 981). In aeroponic culture, BC development was an induced process in barley, whereas in hydroponic culture, it was a kinetic equilibrium process during which 300-400 BCs were released into water daily. The response of root elongation to temperatures (10-35 degrees C) was very sensitive but temperature changes had no great effect on barley BC development. At 35 degrees C, the root elongation ceased whereas BC production still continued, indicating that the two processes might be regulated independently under high temperature (35 degrees C) stress. Fifty microM Al could inhibit significantly BC development by inhibiting pectin methylesterase activity in the root cap of cv. 2000-2 (Al-sensitive) and cv. Humai 16 (Al-tolerant), but 20 microM Al could not block BC development in cv. Humai 16. BCs and their mucigel of barley had a limited role in the protection of Al-induced inhibition of root elongation, but played a significant role in the prevention of Al from diffusing into the meristems of the root tip and the root cap. Together, these results suggested that BC development was a temperature-insensitive but Al-sensitive process, and that BCs and their mucigel played an important role in the protection of root tip and root cap meristems from Al toxicity.

Aluminum↗
PubMed2004

Abnormal monocyte recruitment and collateral artery formation in monocyte chemoattractant protein-1 deficient mice.

Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of collateral artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of collateral artery growth. In a total of 21 MCP-1 -/- as well as 13 of the appropriate genetic background controls ([129Sv/J X C57BI/6J]F1), a femoral artery ligation was performed. Subsequently, a polyethylene catheter, connected to an osmotic minipump, was inserted retrogradely into the occluded femoral artery with the tip pointing upstream. Using this technique, PBS (MCP-1 -/-: n = 13 and C57BI/6J: n = 13) or MCP-1 (JE; MCP-1 -/-: n = 8) was delivered intra-arterially. Seven days after ligation, determination of hind limb flow was assessed by controlled tissue perfusion using differently labeled fluorescent microspheres. MCP-1 -/- mice exhibited a reduction of hind limb flow of 32.9 +/- 9.2% of the unligated hind limb, compared with 55.4 +/- 6.8% in C57BI/6J mice (p<0.01). MCP-1 -/- mice that underwent a subsequent 'rescue' treatment with MCP-1 showed a restoration of flow to a level of 47.4 +/- 9.8% (p = NS compared with PBS-treated C57BI/6J). Specific immunohistochemical staining for monocytes (MOMA-2: MCP-1 -/-, n = 5 and C57BI/6J, n = 5) showed a reduced number of monocytes around developing collateral arteries in the MCP-1 -/- mice. In conclusion, our data show that the absence of MCP-1 causes a strong reduction in flow restoration after femoral artery occlusion, coinciding with a reduced monocyte attraction, emphasizing the central role of this chemokine in the multifactorial process of collateral artery formation.

Animals↗
PubMed2004

Single nucleotide polymorphisms of deoxyribonuclease I and their expression in Chinese systemic lupus erythematosus patients.

BACKGROUND: Previous studies have suggested that interrupted clearance of nuclear DNA-protein complexes after cell death might initiate and propagate systemic lupus erythematosus (SLE). Deoxyribonuclease I (DNaseI) may be responsible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of SLE. The purpose of this study was to genotype the single nucleotide polymorphisms (SNPs) of DNase1 and characterize its gene expression and alternatively spliced transcripts in Chinese patients with SLE in order to understand the pathogenic role of DNase1 in human SLE. METHODS: Four SNPs located at the 3' end of the DNase1 gene, as listed on the SNP website, were selected for analysis. Those SNPs with relatively high heterozygosity were chosen for genotyping in 312 Chinese SLE families using the Taqman minor groove binder (MGB) allelic discrimination method. Haplotypes were constructed and linkage disequilibrium tests were performed using GeneHunter. DNase1 mRNA expression was detected using real-time polymerase chain reaction (PCR), and alternatively spliced transcripts were isolated using capillary electrophoresis. Any effects the specific SNP haplotypes had on DNase1 gene expression and the alternatively spliced transcripts were also assessed. RESULTS: rs179982 and rs1053874 had high heterozygosity, about 0.5 in this Chinese cohort, while rs1059857 was also found to be heterozygous. Analysis of the haplotype combining rs179982-rs1030874 (C-G) and rs179982-rs1030874-rs1059857 (C-G-G) revealed a skewed transmission in favor of affected offspring. DNase1 gene expression was higher in SLE patients than in normal controls (P < 0.001), but this was not related to disease activity or SNP haplotype. Capillary electrophoresis revealed that the pattern of alternatively spliced transcripts in patients differed from that of normal controls. Furthermore, different SNP haplotype combinations generated different transcript patterns in SLE patients. CONCLUSIONS: The SNP haplotypes are in linkage disequilibrium in Chinese SLE patients and may induce the disease through a modification of DNase1 mRNA splicing rather than at the level of mRNA expression. There is a relatively unique transcript band in SLE patients independent of special haplotype, which suggests that other unknown factors might be involved in adjusting gene expression.

Adolescent↗
PubMed2003

Divergent effects of GM-CSF and TGFbeta1 on bone marrow-derived macrophage arginase-1 activity, MCP-1 expression, and matrix metalloproteinase-12: a potential role during arteriogenesis.

Granulocyte/macrophage-colony stimulating factor (GM-CSF) and transforming growth factor (TGF)beta1 induce arteriogenesis in a nonischemic model of femoral artery ligation. Moreover, clinical trials demonstrated an improved collateralization after injection of bone marrow cells. In the present study, the expression of arteriogenic factors in bone marrow-derived macrophages (BMDM) was measured to verify the potential of these cells to influence collateral artery growth. GM-CSF induced in BMDM the expression of monocyte chemoattractive protein (MCP)-1, matrix-metalloproteinase (MMP)-12, and arginase-1-the latter also showing a remarkable increase in activity. During in vivo induced arteriogenesis, the accumulation rate of macrophages around proliferating collaterals was significantly increased. We also show that MCP-1 is found to be mainly expressed in the media of the vessel wall, MMP-12 in macrophages of the adventitia, and arginase at both locations. This study provides for the first time a comprehensive analysis of GM-CSF/TGFbeta1-regulated arteriogenic factors in BMDM and supports the hypothesis that arteriogenesis is a multistage mechanism, including monocyte/macrophage adhesion and transmigration, pro-arteriogenic cytokine expression, degradation of connective tissue, and collagen synthesis regulation. Selective modulation of these mechanisms as well as cell-based therapies supplying arteriogenic factors in vivo point toward new strategies to influence collateral artery growth.

Animals↗
PubMed2003

[Using GST-tag to capture protein interaction of an interferon-inducible systemic lupus associated gene, IFIT1].

OBJECTIVE: To investigate the protein-to-protein interaction of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), a newly discovered systemic lupus erythematosus (SLE) related up-regulated gene, and its possible function. METHODS: Peripheral blood of 40 SLE patients was obtained to extract total RNA and synthesized cDNA. Real-time PCR was used to determine the IFIT1 expression at transcript level. Peripheral blood of another 10 SLE patients was extracted to obtain specimens of white blood cell lysate. Molecular cloning and a modified gluthion S-transferase (GST)-pull down assay were used to capture the protein interacting with IFIT1 in the specimens of white blood cell lysate. MALDI-TOF mass spectrometry (MS) was preformed to identify the captured protein that could interact with IFIT1. Twenty-nine sex and age-matched healthy persons were used as controls. RESULTS: By real-time PCR showed that the IFIT1Delta Ct value (x +/- s) was 2.344 +/- 1.200 in the SLE patients and was 3.734 +/- 1.274 in the controls (P < 0.001), showing a significant up-regulation in SLE patients. IFIT1 was cloned and GST-IFIT1 fusion protein was expressed in Escherichia coli. GST-IFIT1 fusion protein was further purified using Glutathione Sepharose 4B column, and was treated as bait to capture prey from peripheral white blood cell lysate of SLE patients. MALDI-TOF MS detected protein interaction between Rho/Rac guanine nucleotide exchange factor and IFIT1. CONCLUSION: IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor, and regulate the activation of Rho/Rac proteins, thus being involved in the pathogenesis of SLE.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Effect of lipid on proliferation and activation of rat hepatic stellate cells (I).

AIM:To study the effect of lipid (triglyceride and very low-density lipopro tein, VLDL) on proliferation and activation of rat hepatic stellate cells (HSC).METHODS:HSC were isolated and cultured from liver of Wistar rats by in situ perfusion with pronase and collagenase and density gradient centrifugation with Nycodenz.HSC proliferation was examined with MTT colorimetric assay.RESULT: Triglyceride of had a promoting effect on proliferation of HSC (P< 0.05), 25, 50, 100 and 200mg/L had no effects (P >0.05),but 400mg/L had an inhibiting effect (P <0.01). VLDL of 6.25 and 12.5mg/L had no effect on proliferation of HSC (P > 0.05), but increased concentration of VLDL could promote the HSC proliferation (P < 0.05).CONCLUSION:Lipid had an effect on proliferation of HSC. Triglyceride and VLDL may promote HSC proliferation and may be associated with fatty liver and hepatic fibrogenesis.

Journal Article↗
PubMed1998

Study on the role of free fatty acids in proliferation of rat hepatic stellate cells (II).

AIM:To study the role of free fatty acids (arachidonic acid and linoleic acid) in proliferation of rat hepatic stellate cells (HSC).METHODS:HSC were isolated and cultured from liver of Wistar rats by in situ perfusion with pronase and collagenase, and density gradient centrifugation with Nycodenz.MTT colorimetric assay was detected for HSC proliferation.RESULTS:Arachidonic acid and linoleic acid had an effect on proliferation of HSC. 25mg/L of arachidonic acid promoted HSC proliferation (P < 0.01), but 50 and 100mg/L had an inhibitory effect on HSC (P < 0.01),and showed cytotoxity on HSC under inverted microscope; 6.25, 12.5, 25ug/ml of linoleic acid had no effect on HSC proliferation (P > 0.05), but with concentration increasing, 50 and 100mg/L of linoleic acid might promote HSC proliferation (P < 0.05 or 0.01 ).CONCLUSION:Arachidonic acid and linoleic acid may promote HSC proliferation, but increased concentration can have cytotoxity on HSC. Arachidonic acid and linoleic acid might be associated with fatty liver and hepatic fibrogenesis by lipid peroxidation.

Journal Article↗
PubMedDate not supplied

Haptics-based dynamic implicit solid modeling.

This paper systematically presents a novel, interactive solid modeling framework, Haptics-based Dynamic Implicit Solid Modeling, which is founded upon volumetric implicit functions and powerful physics-based modeling. In particular, we augment our modeling framework with a haptic mechanism in order to take advantage of additional realism associated with a 3D haptic interface. Our dynamic implicit solids are semi-algebraic sets of volumetric implicit functions and are governed by the principles of dynamics, hence responding to sculpting forces in a natural and predictable manner. In order to directly manipulate existing volumetric data sets as well as point clouds, we develop a hierarchical fitting algorithm to reconstruct and represent discrete data sets using our continuous implicit functions, which permit users to further design and edit those existing 3D models in real-time using a large variety of haptic and geometric toolkits, and visualize their interactive deformation at arbitrary resolution. The additional geometric and physical constraints afford more sophisticated control of the dynamic implicit solids. The versatility of our dynamic implicit modeling enables the user to easily modify both the geometry and the topology of modeled objects, while the inherent physical properties can offer an intuitive haptic interface for direct manipulation with force feedback.

Algorithms↗