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Biomedical subjects

Zheng-Guo Wang

Publications and source records attributed to Zheng-Guo Wang.

10 recordsLinked to original sources
PubMed2005

Novel TLR4-antagonizing peptides inhibit LPS-induced release of inflammatory mediators by monocytes.

Toll-like receptor 4 (TLR4) has become a new target for combating Gram-negative bacterium-induced sepsis. In this study, we screened peptides that can interact with TLR4 from a random 16-peptide library using yeast two-hybrid system and performed functional identification for the obtained peptides. We got two positive clones out of 1.28x10(7) transformants. The peptides were sequenced and synthesized. Protein sequence comparison confirmed that the two peptides had no homologous proteins. The two peptides were found to significantly inhibit LPS-induced NF-kappaB activation in HEK-293 cells that were transfected with TLR4 cDNA, LPS-induced IkappaBalpha (IkappaB alpha) phosphorylation and NF-kappaB activation in monocytes, and release of IL-1, IL-6, and TNF-alpha by monocytes. We further confirmed that the No. 9 peptide could bind to TLR4 extracellular domain, but the No. 24 peptide could not, suggesting that two novel peptides were identified as the antagonists of TLR4, which significantly inhibited the effects of endotoxin in vitro. The No. 9 peptide may function through binding to TLR4 extracellular domain. Our findings suggest a promising countermeasure against Gram-negative bacterium-induced sepsis.

Cells, Cultured↗
PubMed2005

Silencing effect of recombinant plasmids PPARgamma-pSUPER-EGFP on the expression of peroxisome proliferator-activated receptor gamma.

OBJECTIVE: To investigate the silencing effect of gene encoding peroxisome proliferator-activated receptor gamma (PPARgamma) on the expression of tumor necrosis factor alpha (TNFalpha) by constructing vectors for RNA interference in RAW264.7 cells. METHODS: The pSUPER-EGFP vectors were used to transcribe functional small interfering RNA (siRNA). Four pairs of oligonucleotides (64 nt) targeting PPARgamma gene were inserted into the downstream of the H1 promotor, with their veracity confirmed by double digestion and sequencing. Western blotting and immunofluorescence assay were used to examine the silencing effect of PPARgamma gene in RAW264.7 cells. Meanwhile, the TNFalphalevel was determined by Sandwich ELISA. RESULTS: Compared with other recombinant pSUPER-EGFP vectors (R-pSUPER.EGFP), R-pSUPER.EGFP2 induced the best silencing effect on the expression of PPARgamma in RAW264.7 cells, which played an obvious inhibitory role in down-regulating the TNFalphaexpression after the curcumin and lipopolysaccharide (LPS) stimulation. CONCLUSIONS: PPARgamma-pSUPER-EGFP inducing a silencing effect on the expression of PPARgamma can efficiently play a negative role in controlling the inflammatory responses of RAW264.7 cells.

Journal Article↗
PubMed2004

[Recent advances of protein phosphorylation in proteome].

With the advent of post-genomic era, it is an important task to study the expression, modification and interaction of the total proteins in cells, tissue and organs for proteomics in biological organism. The protein phosphorylation is one of the most popular mechanisms in signal transduction and enzyme modulation. It is estimated that about 2% of the total genes encoded 500 kinases and 100 phosphatases in human genome. As the key point of expression modulation in prokaryotic and eukaryotic cells, the protein phosphorylation and dephosphorylation may help to reveal the status of the life system at the molecular level. The phosphorylation in proteome remains challenging for functional genomics. In the present review, some new advances such as identification and characterization of protein phosphorylation in proteome are summarized.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2003

Intrapulmonary expression of scavenger receptor and CD14 and their relation to local inflammatory responses to endotoxemia in mice.

This study was first designed to investigate systematically the kinetics of surface expression of scavenger receptors (SRs) and CD14 on alveolar macrophages in vivo and in vitro and their relation with local pro- and antiinflammatory responses in endotoxemia. The expression of SR and CD14 in lungs was down- and up-regulated, respectively, in the presence of endotoxemia, which might be due to decreased expression of SR and increased expression of CD14 on the surface of the resident macrophages. Down-regulation of SRs on alveolar macrophages not only induces decreased defensive function of the macrophages, it also enhances lipopolysaccharide (LPS)-induced activation of alveolar macrophages possibly through increasing LPS binding to CD14. Although CD14 is a key receptor responsible for LPS to activate macrophages, both phospholipase C and anti-CD14 antibody can completely inhibit activation of alveolar macrophages initiated by only LPS 1 ng/ml, as determined by tumor necrosis factor-alpha (TNFalpha) production, but it does not significantly change TNFalpha release upon cell stimulation by LPS 10 microg/ml. There was an intrinsic relation of enhanced intrapulmonary pro- and antiinflammatory responses with changes in SR and CD14 expression, which suggests that the down-regulation of SR and up-regulation of CD14 might be an important mechanism for the lung to change from a defense organ to an effector organ during sepsis.

Animals↗
PubMed2003

Road traffic injuries.

The appearance of cars has raised materialistic civilization and living standard to an unprecedented level. Today, it is hard to imagine how we human beings can live without cars. Yet, motor vehicles can cause a great number of deaths and injuries as well as considerable economic losses, which have constituted the global burden. Understanding of the occurrence and development of road traffic injuries will contribute to the prevention and control of crash and to the implementation of "everybody has the right to enjoy health" proposed by WHO.

Accidents, Traffic↗
PubMed2002

Kinetics of mitogen-activated protein kinase family in lipopolysaccharide-stimulated mouse Kupffer cells and their role in cytokine production.

This study was designed to systemically investigate the kinetics of extracellular signal-regulated kinase (ERK) 1/2, p54 c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated Kupffer cells (KC) simultaneously at the levels of protein expression, phosphorylation, and kinase activity, respectively, and their role in mediating pro- and anti-inflammatory cytokines. The protein expression, phosphorylation, and activities of these MAPKs in LPS-stimulated primary mouse KCs were determined with SDS-PAGE and western blotting using nonphosphorylated or phosphospecific antibodies or their corresponding substrates. The levels of TNF-alpha and IL-10 in culture supernatants were measured with ELISA kits. The results revealed that LPS stimulation, although not up- or downregulating the protein expression of ERK1/2, p54JNK, and p38 MAPKs in KCs, could induce rapid and significant activation of these kinases, with parallel profiles of changes in both phosphorylation and kinase activities. Although ERK1/2, p54JNK, and p38 kinases in LPS-stimulated KCs have similar kinetics of activation, the activation of ERK1/2 and p38 kinases was the most prominent. Inhibition of p38 MAPK with SB203580 inhibited the production of TNF-alpha and IL-10 by LPS-stimulated KCs, whereas blockade of ERK1/2 with PD98059 could reduce TNF-alpha production, but did not affect IL-10 production. Furthermore, PD98059 and SB203580 had an additive effect on TNF-alpha production, but PD98059 did not augment the SB203580-induced inhibition of IL-10 production. These data indicate that LPS stimulation, although not inducing any change in protein expression, results in rapid activation of ERK1/2, p54JNK, and p38 kinases in KCs, and that they may have different importance in the regulation of pro- and anti-inflammatory responses by LPS-stimulated KCs.

Animals↗
PubMed2002

[Effect of vascular endothelial growth factor in fracture healing].

OBJECTIVE: To observe the effect of vascular endothelial growth factor (VEGF) in fracture healing and to investigate the influence of VEGF and VEGF antibody in fracture healing. METHODS: One hundred and five rabbits were used to make fracture model in the left radius and randomly divided into control group, VEGF group and VEGF antibody group. VEGF and VEGF antibody were used in the VEGF group and VEGF antibody group respectively, then the blood flow of the fracture ends was measured by single photon emission computed tomography (SPECT) 8, 24, 72 hours, 1, 3, 5 and 8 weeks after fracture, the X-ray films of the fracture sites were taken after 1, 3, 5 and 8 weeks to observe the fracture healing. RESULTS: The blood flow of the fracture ends in the VEGF group increased during a period from 8 h to 3 wk after fraction when compared with that of the control group, and no obvious difference was seen on the X-ray films between the two groups. In the VEGF antibody group, the blood flow of the fracture ends decreased obviously when compared with that of the control group. The fracture healing process was interfered seriously and nonunion change was seen in the fracture site. CONCLUSION: The lack of VEGF will interfere with the fracture healing process and result in nonunion in the fracture site. Administration of ectogenous VEGF may promote fracture healing by increasing the blood flow of the fracture ends.

Animals↗
PubMed2002

[Ultrastructural features of cultured rat cortical astrocytes with stretch-induced injury].

OBJECTIVE: To investigate the changes of ultrastructural features of cultured rat cortical astrocytes after stretch-induced injury. METHODS: Rat cortical astrocytes isolated from 1- to 2-day-old rats were cultured till confluency, and then plated in tissue culture wells with flexible silastic bottom after purification. A computer-controlled device was used to produce stretch-induced injury in the astrocytes with the imposed pressure of 50, 150, and 250 kPa respectively, followed by observation of the ultrastructural changes in the astrocytes with light and electron microscopy. RESULTS: Obvious ultrastructural destruction of the astrocytes occurred when the imposed stretch pressure was 50 kPa, and scanning electron microscopy demonstrated increased intercellular space and laceration of the cell body and its processes. Transmission electron microscopy revealed mitochondria swelling 1 h after stretch-induced injury and 6 h after the injury, vacuolar degeneration of the mitochondria occurred. Increased stretch pressure caused further decrease in the amount of glial filaments and densification of astrocytes. CONCLUSIONS: Stress, even at a relatively small scale, can cause disruption of intercellular juncture and ultrastructural change of the cultured astrocyte, which may be related with extensive brain edema after traumatic brain injury.

Animals↗
PubMed2002

Induction of acute hepatic injury by endotoxin in mice.

OBJECTIVE: To investigate the changes of scavenger receptor (SR) and CD14 in Kupffer cells in endotoxemia in order to uncover the mechanism of the liver to turn a defense organ into effector one in sepsis. METHODS: Mouse models of endotoxemia of different severity were reproduced by injection of different doses of lipopolysaccharide (LPS) via the tail vein. The expression of SR and CD14 in the liver was assayed by immunohistochemistry and was subsequently analyzed with an image analysis system. The levels of TNF-alpha and IL-6 in liver tissue were determined with ELISA. RESULTS: The expression of SR in the liver in the high-dose group was markedly decreased one hour after injection of LPS, and also in the low-dose group at 3 hours. The expression of SR in the liver in the two groups was shown to be progressively decreased with the time prolonged. There was significant difference in average optical density (OD) values of SR between the two groups. The expression of CD14 in the two groups was shown to be significantly increased one hour after injection of LPS, and more significantly with the time prolonged. But there was no significant difference in OD values of CD14 between the two groups. The contents of intrahepatic proinflammatory mediators TNF-alpha, IL-6, ALT and TBIL were significantly increased after injection of LPS. Correlation analysis revealed that the changes of TNF-alpha, IL-6, ALT, and TBIL were negatively correlated with the expression of SR, and positively with the expression of CD14. CONCLUSION: The up-regulation of CD14 expression and down-regulation of SR expression on Kupffer cells might be one of the important mechanisms for the conversion of Kupffer cells from immune defensive to inflammatory response cells in acute hepatic injury.

Acute Disease↗