Plasma glutamate-modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury-induced acute lung injury.

The bone marrow-derived cell (BMDC)-associated inflammatory response plays a key role in the development of acute lung injury (ALI). Activation of adenosine A2A receptor (A2AR) is generally considered to be antiinflammatory, inhibiting BMDC activities to protect against ALI. However, in the present study, we found that in a mouse model of neurogenic ALI induced by severe traumatic brain injury (TBI), BMDC A2AR exerted a proinflammatory effect, aggravating lung damage.

Local glutamate level dictates adenosine A2A receptor regulation of neuroinflammation and traumatic brain injury.

During brain injury, extracellular adenosine and glutamate levels increase rapidly and dramatically. We hypothesized that local glutamate levels in the brain dictates the adenosine-adenosine A(2A) receptor (A(2A)R) effects on neuroinflammation and brain damage outcome. Here, we showed that, in the presence of low concentrations of glutamate, the A(2A)R agonist 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid (CGS21680) inhibited lipopolysaccharide (LPS)-induced nitric oxide synthase (NOS) activity of cultured microglial cells, an effect that was dependent on the protein kinase A (PKA) pathway.

Clinical relevance of IL-1beta promoter polymorphisms (-1470, -511, and -31) in patients with major trauma.

Recent reports have indicated that IL-1[beta] is excessively released into the circulation during sepsis, and the expression level is closely correlated with the clinical course. Polymorphisms in the promoter region of IL-1B have been shown to affect LPS-induced IL-1[beta] transcription in vitro and IL-1[beta] plasma levels in healthy adults and to confer susceptibility to inflammatory diseases. However, it is not clear whether they confer susceptibility to sepsis after major trauma.

Distributions of glucocorticoid receptor gene polymorphisms in a Chinese Han population and associations with outcome after major trauma.

Aim: To investigate in a Chinese population the occurrence of polymorphisms Bcl I, N363S and ER22/23EK in the glucocorticoid receptor and their association with outcome of trauma.

Methods: In all, 266 healthy volunteers and 95 victims of major trauma were recruited. The presence of glucocorticoid receptor polymorphisms (ER22/23EK, N363S and Bcl I) was sought by restriction fragment length polymorphism analysis.

[Burn-blast combined injury].

Burn-blast combined injury is caused by two injury factors--heat and blast, which inflict the body at the same time or in sequence. The incidence of the combined injury is high either in wartime or in peacetime, and the mortality is much higher than that of an injury due to either one injury factor. In order to elucidate the mechanism, characteristics of the injury and the treatment of the combined injury, lots of studies were carried out both at home and abroad.

Expressions of scavenger receptor, CD14 and protective mechanisms of carboxymethyl-beta-1, 3-glucan in posttraumatic endotoxemia in mice.

Background: Previous studies in our laboratory have demonstrated the downregulation of surface expression of scavenger receptor (SR) and upregulation of CD14 in the presence of endotoxemia, which directly correlates to the excessive inflammatory response in lung injuries. This study aims to analyze the dynamics of the expressions of SR and CD14 in traumatic endotoxemia, and to investigate the receptor mechanism of immunomodulator, carboxymethyl-beta-1, 3-glucan (CMG), on the protection of traumatic infections.

Methods: By using a sublethal fracture plus endotoxemia model, experimental mice were assigned to sham group (Sham), trauma group (T), traumatic endotoxemia group (TE), and traumatic endotoxemia plus CMG group (TE + C).

Vascular endothelial growth factor and its receptor expression during the process of fracture healing.

Objective: To study the expression regularity of vascular endothelial growth factor (VEGF) during the process of fracture healing, and the type of VEGF receptor expressed in the vascular endothelial cells of the fracture site.

Methods: The fracture model was made in the middle part of left radius in 35 rabbits. The specimens from the fracture site were harvested at 8, 24, 72 hours and 1, 3, 5, 8 weeks, and then fixed, decalcified, and sectioned frozenly to detect the expression of VEGF and its receptor at the fracture site by in situ hybridization and immunochemical assays.

Identification of interleukin-6 promoter polymorphisms in the Chinese Han population and their functional significance.

Objective: Interleukin-6 (IL-6) is a pivotal cytokine in both innate and adaptive immunity. Several polymorphisms in the IL-6 promoter have been reported in Western populations. However, little is known about their occurrence in the Chinese population.

[Different effects of adenosine A2A receptors in the models of traumatic brain injury and peripheral tissue injury].

Recently, activation of the adenosine A2A receptors has been shown to exert protection against peripheral tissue injuries but aggravation in the central nervous system (CNS) injuries. To explore the different effects of adenosine A2A receptors and try to perform some new treatment strategies for peripheral tissue and CNS traumas, we constructed the mouse models of skin trauma, skin combined radiation-impaired wound and traumatic brain injury (TBI), respectively. Wild type mice and A2A receptor gene knockout mice were both used in the experiments.

Regulation of vascular endothelial growth factor on the expression of fracture healing-related factors.

Objective: To study the effect of vascular endothelial growth factor (VEGF)and anti-VEGF on the expression of fracture healing-related factors and observe pathological changes at fractured sites.

Methods: Fracture models were established in 105 New Zealand white rabbits and they were randomly divided into control group, VEGF group and anti-VEGF group. The relevant factors expression at fractured sites was assayed and pathological changes were observed in decalcified samples at 8, 24, 72 hours and 1,3,5,8 weeks after fracture.

[Relationship of myeloid differentiation-2 gene promoter polymorphisms with susceptivity of complications after severe trauma in Chinese Han population].

Objective: To investigate the polymorphisms of myeloid differentiation-2 (MD-2) gene promoters, and to explore whether such polymorphisms are associated with the susceptibility to multiple organ dysfunction syndrome (MODS) and sepsis in Chinese Han population.

Methods: Using polymerase chain reaction-restriction fragment length polymorphism method, the authors detected the single nucleotide polymorphisms of the promoter region of MD-2 gene at position - 1625C/G in 105 severe trauma patients (42 with sepsis). The organ function was scored.

[Establishment of a selective inactivation adenosine A2A receptors mice model].

Objective: To establish a mice model with selective inactivation adenosine A2A receptors (A2ARs) in peripheral white blood cells (PWBC).

Methods: A2ARs were selectively inactivated in PWBCs by transplanting bone marrow cells (BMCs) from A2AR knockout (KO) mice into their wild type (WT) littermates after a single total body irradiation of 9.5 Gy or fractionated total body irradiation of 6.

Functional significance of the TLR4/11367 polymorphism identified in Chinese Han population.

Toll-like receptor 4 (TLR4) is the central signaling receptor for lipopolysaccharide (LPS) in mammals. This study was designed to investigate the functional significance of the G11367C polymorphism, which is a novel variant we identified in the 3' untranslated region of TLR4 gene in Chinese Han population. Three hundred seventy healthy volunteers were selected.

Comparative observation of protective effects of earplug and barrel on auditory organs of guinea pigs exposed to experimental blast underpressure.

Objective: To explore the protective effects of earplug and barrel on auditory organs of guinea pigs exposed to experimental blast underpressure (BUP).

Methods: The hearing thresholds of the guinea pigs were assessed with auditory brainstem responses (ABR). The traumatic levels of tympanic membrane and ossicular chain were observed under stereo-microscope.

[The relationship of the expression of principal pattern recognition receptor with the pulmonary injury in abdominal infection-induced sepsis].

Objective: In order to investigate the evidence of the synergistic effects of bacterial components, to observe the relationship of the expression of lipopolysaccharide (LPS) receptors [CD14, Toll-like receptor 4 (TLR4), scavenger receptor (SR)], lipoprotein receptor (TLR2) and bacterial DNA receptor (TLR9) with pulmonary injury in abdominal infection-induced sepsis.

Methods: 30 mice were used and randomly divided into cecal ligation puncture (CLP) (n = 15) and sham (n = 15) groups. The animals were respectively sacrificed 8, 12 and 24 (each point n = 5) hours following CLP and sham CLP.

Effects of haplotypes in the interleukin 1beta promoter on lipopolysaccharide-induced interleukin 1beta expression.

Previous studies have indicated that there are 3 common haplotypes composed of the -1470, -511, and -31 loci in the interleukin 1beta (IL-1beta) promoter in the Chinese population. The purpose of this study was to investigate the relationship between these haplotypes and lipopolysaccharide (LPS)-stimulated IL-1beta expression by whole blood leukocytes in vitro and to evaluate the effects of these haplotypes on IL-1beta gene transcription. Genomic DNAs were obtained from 105 healthy subjects.

[Expression of thrombospondin 2 during the repair process after alkali burn injury of cornea in mice].

Objective: To explore the expression of thrombospondin 2 (TSP2) during the repair process after alkali burn injury to cornea in mice.

Methods: Forty mice were employed in the study. The murine corneal alkali burn model was reproduced (n = 35) as experimental group (E), and the mice were randomly divided into control (C, n = 5) and experimental (E, n = 35) groups.

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).

[The synergistic effects of lipopolysaccharide, bacterial lipoprotein and bacterial DNA on mouse alveolar macrophage activation].

Objective: To investigate the synergistic effects of lipopolysaccharide (LPS), bacterial lipoprotein (BLP), and bacterial DNA on the expression of pattern recognition receptors (PRRs) on the cell surface of mouse alveolar macrophages and cellular activation at the level of receptor and its possible mechanism.

Methods: Mouse alveolar macrophages were isolated, cultivated and randomly divided into 7 groups: control group, LPS group, CpG oligonucleoetide (CpG-ODN) group, BLP group, LPS + BLP group, LPS + CpG-ODN group, and LPS + BLP + CpG-ODN group. Six hours later the supernatants were collected to detect the level of tumor growth factor alpha (TNFalpha) by ELISA.

[The effects of TNF alpha and IFN gamma on the expression of pattern recognition receptors on the surface of mouse alveolar macrophages].

Objective: To investigate the effects of tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) on the expression of pattern recognition receptors (PRRs) on the surface of mouse alveolar macrophages.

Methods: Alveolar macrophages from mouse were cultured in DMEM supplemented with 10% (V/V) endotoxin-free calf serum. After the alveolar macrophages were stimulated with TNF alpha and IFN gamma (concentration, 20 ng/ml) for 3 h, 6 h and 12 h, the expression of PRRs, including cluster of differentiation 14 (CD14), scavenger receptor (SR), toll-like receptor 4 (TLR4), TLR2 and TLR9 mRNA and proteins were examined by RT-PCR and immunohistochemistry.

[The role of myeloid differentiation protein-2 in lipopolysaccharide-induced cellular activation of human endothelial cells].

Objective: To investigate the expression of myeloid differentiation protein-2 (MD-2) in the human endothelial cells and its role in lipopolysaccharide (LPS)-induced NF-kappaB activation in endothelial cells.

Methods: In vitro cultured human umbilical vein endothelial cells (HUVEC) were employed in the study. The expression of MD-2 mRNA and protein, and the effect of LPS on the expression of its mRNA and protein were assessed with RT-PCR and Western blotting.

Therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation in rats.

Objective: To investigate the therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation.

Methods: 108 Wistar rats weighing (200 g+/-30 g) were randomly divided into a sham shock (SS) group (n=36), a hemorrhagic shock resuscitation (HS) group (n=36) and a hemorrhagic shock cisapride treated (HSC) group (n=36). Sampling at 1, 2 and 4 hours after resuscitation was done and 6 samples for each observation item were taken.

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.

[Comparative study on physical parameters and biological effects of blast wave on plateau and on plain].

Objective: To compare the physical parameters and biological effects of blast wave on plateau and on plain.

Methods: Twenty-five pigs were divided into two groups: plateau group (n=15) and plain group (n=10). They were placed either 5 meters or 6 meters away from the site of explosion.