Soluble Collagen VI Induces Tyrosine Phosphorylation of Paxillin and Focal Adhesion Kinase and Activates the MAP Kinase Erk2 in Fibroblasts

Signals from the extracellular matrix can modulate cellular differentiation and gene expression. We have shown previously that in contrast to other extracellular matrix molecules pepsin-solubilized collagen VI (CVI) can stimulate DNA synthesis of various mesenchymal cell types, apparently independent of integrin-mediated signal transduction. In order to further elucidate collagen VI-induced signaling events, we exposed mouse 3T3 fibroblasts and human HT1080 fibrosarcoma cells to soluble CVI. CVI induced tyrosine phosphorylation of proteins that associate with focal adhesions, such as paxillin, focal adhesion kinase (FAK), and p130CAS. Furthermore, it activated the mitogen-activated protein kinase, erk2. Kinetic analysis showed that these phosphorylations were transient, reaching a maximum after 5 min for transformed HT1080 cells and 30 min for 3T3 fibroblasts. These effects were partly inhibited by a beta1-integrin function blocking antibody and by single chains of CVI. Our results indicate that soluble fragments of native collagen VI, a ubiquitous component of the interstitial extracellular matrix, can mediate stimulation of DNA synthesis via tyrosine phosphorylation of paxillin, FAK, p130CAS, and erk2 in the absence of classical growth factors. Thus, CVI may serve as a matrix-derived sensor that allows for rapid reconstitution of a tissue defect by activating nearby mesenchymal cells.     

Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives

Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects.Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition.In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC₅₀ values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC₅₀:0.42?nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.     

Effects of Naringenin on Oxidative Stress and Histopathological Changes in the Liver of Lead Acetate Administered Rats

Lead has several adverse effects on the body due to one of the environmental pollutants. We aimed to determine the effects of naringenin on the oxidative stress and the hepatic damage against lead acetate treatment in the liver of male rats. Naringenin was administered by orogastric gavage (50 mg/kg) and lead acetate was given as daily 500 parts per million in drinking water for 4 weeks. Lead and antioxidant activities were measured, and histopathological evaluation was performed in the liver. Lead concentrations, malondialdehyde, and antioxidant activity were restored by the naringenin. The grade of necrosis, hydropic degeneration, and hepatic cord disorganization was decreased by the naringenin. However, there were no differences in the degree of sinusoidal congestion, hepatic steatosis, and capsular fibrosis between lead acetate and naringenin + lead acetate groups. We can suggest that naringenin has antioxidant and chelating effects in the liver. Nevertheless, this effect is not enough against the lead acetate induced hepatic injury.     

Beneficial effects of dexpanthenol on mesenteric ischemia and reperfusion injury in experimental rat model

Background and aim It has been reported that intestinal ischemia–reperfusion (I/R) injury results from oxidative stress caused by increased reactive oxygen species. Dexpanthenol (Dxp) is an alcohol analogue with epitelization, anti-inflammatory, antioxidant, and increasing peristalsis activities. In the present study, the aim was to investigate protective and therapeutic effects of Dxp against intestinal I/R injury. Materials and methods Overall, 40 rats were assigned into five groups including one control, one alone Dxp, and three I/R groups (40-min ischemia; followed by 2-h reperfusion). In two I/R groups, Dxp (500?mg/kg, i.m.) was given before or during ischemia. The histopathological findings including apoptotic changes, and also tissue and serum biochemical parameters levels, were determined. Oxidative stress and ileum damage were assessed by biochemical and histological examination. In the control (n?=?8) and alone Dxp (n?=?8; 500?mg/kg, i.m. of Dxp was given at least 30?min before recording), groups were incised via laparotomy, and electrical activity was recorded from their intestines. In this experiment, the effect of Dxp on the motility of the intestine was examined by analyzing electrical activity. Results In ileum, oxidant levels were found to be higher, while antioxidant levels were found to be lower in I/R groups when compared with controls. Dxp approximated high levels of oxidants than those in the control group, while it increased antioxidant values compared with I/R groups. Histopathological changes caused by intestinal I/R injury and histological improvements were observed in both groups given Dxp. In the Dxp group, electrical signal activity markedly increased compared with the control group. Conclusions Here, it was seen that Dxp had protective and therapeutic effects on intestinal I/R injury and gastrointestinal system peristaltism.     

Effect of statins on coronary blood flow after percutaneous coronary intervention in patients with stable coronary artery disease

Aims

Statins have favourable effects on the vascular system. However, few data are available regarding the effect of these drugs on patients undergoing percutaneous coronary intervention (PCI). We sought to determine the impact of prior statin use on coronary blood flow after PCI in patients with stable coronary artery disease (CAD) by using the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC).

Methods

A total of 80 consecutive eligible patients (mean age: 60 ± 7 years, 65?% male) with the diagnosis of stable CAD who were hospitalised for elective PCI were retrospectively enrolled in our study. The study population was divided into two groups according to statin use at least 6 months before PCI. Group 1 comprised of 51 patients (67?% male; mean age: 58 ± 4 years) taking statins and group 2 comprised of 29 patients (62?% male; mean age: 60 ± 3 years) not taking statins. PCI was applied to de novo type A lesions. CTFC was calculated for the treated vessels at baseline and after PCI.

Results

The two groups had similar characteristics in terms of age, sex, concomitant medications, lesion characteristics, pre-procedural CTFC, lipid parameters, and risk factors for CAD. Post-PCI CTFC (16 ± 3 vs. 22 ± 5, p = 0.01) and hs-CRP (2.1 ± 0.7 mg/l vs. 6.1 ± 2 mg/l, p = 0.01) in patients receiving statins before PCI were significantly lower than in patients without statin therapy. Multiple logistic regression analysis showed that statin pre-treatment (OR 2.5, 95?% CI 1.2 to 3.8, p < 0.001) and hs-CRP level (OR 1.8, 95?% CI 1.2 to 2.4, p = 0.001) were independent predictors of post-PCI CTFC.

Conclusions

In patients with stable CAD undergoing PCI, receipt of long-term statin therapy was associated with improvement in epicardial perfusion after PCI.