Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor.

Background/aims: Although it has been reported that somatostatin (SOM) upregulated the level of 90-kD heat shock protein (Hsp90), which participates in the inflammatory regulation by its client proteins, such as glucocorticoid receptor (GR), it remains unclear if it has a protective role against acute lung injury (ALI).

Methods: ALI model was established by the injection of oleic acid (OA) into the tail vein of mice. Lung injury was assessed by histological analysis, lung water content and arterial blood gases.

Chronic caffeine exposure attenuates blast-induced memory deficit in mice.

Objective: To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms.

Methods: Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury.

Adenosine A2A receptor deficiency alleviates blast-induced cognitive dysfunction.

Traumatic brain injury (TBI), particularly explosive blast-induced TBI (bTBI), has become the most prevalent injury among military personnel. The disruption of cognitive function is one of the most serious consequences of bTBI because its long-lasting effects prevent survivors fulfilling their active duty and resuming normal civilian life. However, the mechanisms are poorly understood and there is no treatment available.

Dexamethasone inhibits U937 cell adhesion via the down-regulation of ROCK1 activity.

Objective: To explore the effect of dexamethasone (DEX) on monocyte adhesion function and its underlying mechanism.

Methods: The effects of DEX and fasudil on adhesion of cultured U937 monocytes to human umbilical vein endothelial cells (HUVEC) following stimulation with phorbol myristate acetate (PMA) were studied; Changes in the Rho-associated coiled-coil protein kinase 1 (ROCK1) protein content and activity were evaluated.

Results: DEX and fasudil significantly inhibited U937 cell adhesion rates under PMA stimulation and inhibited ROCK1 activity.

Roles of Rho-associated coiled-coil protein kinase in multiple cell behaviors.

Rho-associated coiled-coil protein kinase (ROCK) is a serine/threonine kinase that belongs to AGC family of kinases. By inducing the formation of stress fibers and reorganizing the cytoskeleton, it is involved in many biological behaviors of cells including cell contraction, cell migration, cell division, and morphological changes, and thus exerts important roles in regulating the multiple functions of cells.

Ski, a modulator of wound healing and scar formation in the rat skin and rabbit ear.

We recently demonstrated that Ski is a novel wound healing-related factor that promotes fibroblast proliferation and inhibits collagen secretion. Here, we show that increasing local Ski expression by gene transfer not only significantly accelerated wound healing by relieving inflammation, accelerating re-epithelialization and increasing formation of granulation tissue, but also reduced scar formation by decreasing collagen production in rat dermal wounds. Similarly, ski gene transfer accelerated wound healing, reduced the protuberant height and volume of scars and increased collagen maturity in a hypertrophic scar model in the rabbit ear.

[Effect of (S)-4C3HPG on brain damage in the acute stage of moderate traumatic brain injury model of mice and underlying mechanism].

The aim of this study is to investigate the effect of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG], a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, on impairment in a cortical impact model of traumatic brain injury (TBI) in mice and to elucidate the possible mechanisms. Mice were injected (i.p.

[Effect of small interfering RNA-mediated Smad3 gene silencing on transforming growth factor-beta1-induced bi-directional effects on skin fibroblast proliferation].

Objective: To study the role of Smad3 in transforming growth factor-beta1 (TGF-beta1)-induced bi-directional effects on skin fibroblast proliferation.

Methods: The Smad3 small interfering (siRNA) plasmid was constructed using a pSUPER vector. The efficiency of cell transfection was detected by fluorescence microscopy, and the inhibitory effect of the plasmid was assessed by real-time quantitative RT-PCR and immunohistochemistry.

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.

Adenosine A2A receptors in both bone marrow cells and non-bone marrow cells contribute to traumatic brain injury.

Adenosine A2A receptors (A(2A)Rs) in bone marrow-derived cells (BMDCs) are involved in regulation of inflammation and outcome in several CNS injuries; however their relative contribution to traumatic brain injury (TBI) is unknown. In this study, we created a mouse cortical impact model, and BMDC A(2A)Rs were selectively inactivated in wild-type (WT) mice or reconstituted in global A(2A)R knockout (KO) mice (i.e.

Genetic variations of heat shock protein 84 in mice mediate cellular glucocorticoid response.

Heat shock protein 90 (Hsp90), encoded by hsp84 and hsp86 in mice, has been confirmed to modulate glucocorticoid receptor (GR) function; however, the contribution of Hsp90 in glucocorticoid (GC) sensibility/resistance has received less attention. Previously, we found that genetic variations of Hsp84 are related to differences in the in vivo GC-GR responses between BALB/c and C57BL/6 mice suffering from traumatic injury. To evaluate the modulation of Hsp84 polymorphisms on the GC response, we used a cellular heat-stress injury (HSI) model combined with a transgene-plasmid infection approach and assessed HSI-induced cellular damage and GR nuclear translocation, with or without dexamethasone pretreatment.

Differential alteration of heat shock protein 90 in mice modifies glucocorticoid receptor function and susceptibility to trauma.

Heat shock protein 90 (Hsp90), encoded by the murine hsp84 and hsp86 genes in mice, is a pivotal regulator of glucocorticoid receptor (GR) function in the hypothalamus-pituitary-adrenal axis and affords stress protection. To explore the underlying molecular mechanisms of strain susceptibility to traumatic stress, we investigated the alteration by Hsp90 of the function of the glucocorticoid-glucocorticoid receptor (GC-GR) pathway in attenuating stress responses in C57BL/6 and BALB/c mice using the whole-body blast injury (WBBI) model. We found that C57BL/6 mice had a lower WBBI-induced mortality, higher nuclear GR level, and higher glucocorticoid-response element (GRE) binding activity than BALB/c mice.

[H19 expression in placenta with pre-eclampsia].

Objective: To explore the role of H19 imprinting in etiology of pre-eclampsia.

Methods: Placentas of 24 women with pre-eclampsia (3 with mild pre-eclampsia and 21 with severe pre-eclampsia) and 50 healthy pregnant women at full term (control) were collected during selected cesarean delivery between August 2007 and March 2008. The statuses of H19 imprinting with placental tissues from normal pregnancy and patients with pre-eclampsia were identified upon polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

[Propofol provides ischemic postconditioning on myocardial ischemia-reperfusion injury in rats].

Objective: To investigate whether the infusion of propofol during early reperfusion provides ischemic postconditioning (I-postC) on myocardial ischemia-reperfusion injury in rats.

Methods: Sixty adult rats were randomly divided into 5 groups (n = 12 each): sham operation (group S); normal saline (group C); propofol 1 mg/kg (group P1); propofol 2 mg/kg (group P2); propofol 5 mg/kg (group P3). The left anterior descending coronary artery (LAD) was occluded for 60 min and reperfused for 120 min.

[Association of glucocoid receptor binding activity and heat shock protein expressions after acute lung injury in mice].

Objective: To study the association between decreased ligand binding activity of glucocoid receptor (GR) and heat shock protein 90 (Hsp90), the molecular chaperone of GR, after acute lung injury (ALI) in mice.

Methods: In mouse models of oleic acid-induced ALI, the levels of GR, Hsp90 and Hsp70 were dynamically observed using Western blotting, and the binding capacity and binding affinity of GR assessed with radioligand binding assay.

Results: After ALI, pulmonary edema was significantly aggravated in the mice with significantly increased lung body index and lung water ratio.

[Construction and verification of bait protein RGS4-fusion expression plasmid in yeast two-hybrid system].

Objective: To research the interaction between glucocorticosteroid receptor domains and regulator of G protein signaling 4 (RGS4) protein.

Methods: The RGS4 gene was used as the bait protein gene to construct the fusion bait expression plasmid of yeast two-hybrid. The whole encoding sequence of RGS4 gene was amplified by RT-PCR method.