Alagebrium chloride protects the heart against oxidative stress in aging rats.

To investigate the possible effects of alagebrium chloride (ALT-711) on oxidative stress (OS) process in aging hearts, we examined the role of ALT-711 in cardiac function and OS in the heart of aging rats. Increased mitochondrial DNA (mtDNA) deletion as well as nearly a twofold increase in advanced glycation end products (AGEs) accumulation were observed in aging heart, whereas only about 50% of the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were seen. However, after treatment with ALT-711, preserved cardiac diastolic function accompanied with reduced mtDNA deletion and about 30% of AGEs decrease was observed in aging hearts.

[Heat shock protein 27 attenuated doxorubicin-induced myocardial damage by reducing cardiomyocyte apoptosis, mitochondria damage and protein carbonylation].

Objective: Oxidative stress and apoptosis play a critical role in the pathogenesis of congestive heart failure (CHF) induced by doxorubicin (Dox) or ischemia/reperfusion. Heat shock protein 27 (Hsp27) could reduce oxidative stress induced apoptosis in various cell types in vitro and attenuate ischemia/reperfusion induced cardiac dysfunction in isolated perfused mouse heart. In this study, we investigated the impact of Hsp27 overexpression on oxidative stress and apoptosis in Dox-induced mice cardiac dysfunction model.

Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro.

Gastrin and cyclooxygenase-2 (COX-2) play important roles in the carcinogenesis and progression of gastric cancer. However, it remains unknown whether the combination of cholecystokinin-2 (CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer. Here, we demonstrated that the combination of AG-041R (a CCK-2 receptor antagonist) plus NS-398 (a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition, apoptosis induction, down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.

Heat shock protein 27 regulates oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via reactive oxygen species generation and Akt activation.

Background: Increased reactive oxygen species (ROS) formation, which in turn promotes cardiomyocytes apoptosis, is associated with the pathogenesis and progression of various cardiac diseases such as ischemia and heart failure. Recent studies have shown that over expression of heat shock protein 27 (Hsp27) confers resistance to cardiac ischemia/reperfusion injury. However, not much is known about the regulation of myocyte survival by Hsp27.

[Overexpression of heat shock protein 27 reduces mortality and attenuates cardiac dysfunction induced by doxorubicin in a transgenic mouse model].

Objective: To observe the effects of heat shock protein 27 (Hsp27) overexpression on doxorubicin (Dox) induced mortality and cardiac dysfunction in a transgenic (TG) mouse model.

Methods: A linear DNA constituted of alpha-myosin heavy chain (alpha-MHC) promoter, human Hsp27cDNA and poly A was microinjected into fertilized eggs to generate transgenic mice and mice containing the transgene were identified by polymerase chain reaction and independent transgenic lines were established. Following successful transmission, tissues including heart, lung, liver, brain, skeleton muscle, spleen and kidney were screened by Western blot to confirm the cardiac specific expression of the transgene.

[Adeno-associated virus-mediated CD40 ligand transfer into human lung cancer cells].

Objective: To investigate the transduction efficiency of serotype 1, 2, 5, 6, 7, 8, 9, 10 recombinant adeno-associated viruses (rAAV) in human lung cancer cell line A549 cells and compare the transduction efficiency of conventional AAV vectors with that of self-complementary AAV (scAAV) vectors. Furthermore, the capacity of A549 cells expressing transgenic CD40L to stimulate dendritic cells (DCs) was evaluated.

Methods: Lung cancer A549 cells were infected with 1 x 10(4) particules per cell of AAV encoding the green fluorescent protein (GFP) or human CD40L driven by CMV promotor, and transgene expression was analyzed by flow cytometry and fluorescence microscopy.

[Effects of gastrin receptor antagonist and cyclooxygenase-2 inhibitor on proliferation and apoptosis of gastric cancer cell].

Objective: To investigate the regulative roles of the gastrin receptor antagonist proglumide and the specific cyclooxygenase (COX)-2 inhibitor NS-398 on the proliferation and apoptosis of gastric cancer cells.

Methods: Human gastric cancer cells of the line MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. Subconfluent cell cultures were treated with proglumide at a final concentration of 5 mmol/L, NS-398 at a final concentration of 10.

Influences of Helicobacter pylori on cyclooxygenase-2 expression and prostaglandinE2 synthesis in rat gastric epithelial cells in vitro.

Background And Aim: It is known that cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasia and Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. The present study aimed to elucidate the effects of H.

Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis.

Objective: To investigate the expression of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in gastric carcinomas, and to correlate this expression with clinicopathological parameters and angiogenesis.

Methods: Ninety-six resected tumor specimens from patients with gastric carcinoma were obtained, and 30 corresponding paracancerous normal tissues were randomly selected as a control. Immunohistochemical staining was used for detecting the expression of COX-2 and MMP-9.

[Relationship between cyclooxygenase- 2 expression and angiogenesis in patients with gastric cancer].

Objective: To investigate COX-2 expression in patients with gastric cancer and its relationship with angiogenesis and clinicopathologic features of gastric cancer.

Methods: COX-2 expression and CD34-stained microvessel density (MVD) were detected by immunohistochemical methods in specimens from 96 patients with gastric cancer. The correlations among COX-2 expression, MVD and clinicopathologic features were analyzed.

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions.

Aim: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions.

Methods: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1,000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy.

[Effects of hsf1 genotype on the constitutive expression of alphaB-crystallin in mice myocardium].

Aim: Try to clarify the effects of HSF1 gene on the constitutively expressed alphaBC.

Methods: To investigate the levels of constitutively expressed alphaB-Crystallin (alphaBC) in hsf1 knockout (hsf1 -/-) and hsf1 wild type (hsf1 +/+) mice myocardium by Western blot and immunohistochemistry.

Results: The alphaBC levels in hsf1 -/- and hsf1 +/+ were 68.