The Octadecaneuropeptide ODN Protects Astrocytes against Hydrogen Peroxide-Induced Apoptosis via a PKA/MAPK-Dependent Mechanism

Astrocytes synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN) an endogenous ligand of both central-type benzodiazepine (CBR) and metabotropic receptors. We have recently shown that ODN exerts a protective effect against hydrogen peroxide (H(2)O(2))-induced oxidative stress in astrocytes. The purpose of the present study was to determine the type of receptor and the transduction pathways involved in the protective effect of ODN in cultured rat astrocytes. We have first observed a protective activity of ODN at very low concentrations that was abrogated by the metabotropic ODN receptor antagonist cyclo(1-8)[DLeu(5)]OP, but not by the CBR antagonist flumazenil. We have also found that the metabotropic ODN receptor is positively coupled to adenylyl cyclase in astrocytes and that the glioprotective action of ODN upon H(2)O(2)-induced astrocyte death is PKA- and MEK-dependent, but PLC/PKC-independent. Downstream of PKA, ODN induced ERK phosphorylation, which in turn activated the expression of the anti-apoptotic gene Bcl-2 and blocked the stimulation by H(2)O(2) of the pro-apoptotic gene Bax. The effect of ODN on the Bax/Bcl-2 balance contributed to abolish the deleterious action of H(2)O(2) on mitochondrial membrane integrity and caspase-3 activation. Finally, the inhibitory effect of ODN on caspase-3 activity was shown to be PKA and MEK-dependent. In conclusion, the present results demonstrate that the potent glioprotective action of ODN against oxidative stress involves the metabotropic ODN receptor coupled to the PKA/ERK-kinase pathway to inhibit caspase-3 activation.     

Aneurysm and Helicobacter pylori relationship: the seropositivity of CagA, VacA and other antigens of Helicobacter pylori in abdominal and ascending aortic aneurysms

Helicobacter pylori is thought to be related to atherosclerosis and aneurysm development. We aimed to detect virulance factors of H. pylori and examine the potential etiopathogenetic relationship between aortic aneurysm and H. pylori, 58 abdominal aortic aneurysm (AAA) and 38 ascending aortic aneurysm (AsAA) cases and 57 Healty control group (HCG) were included. We investigated H. pylori IgG by ELISA and virulance factors by Western-Blot (WB) method. No difference was found between AAA (67.24%), AsAA (73.68%) and HCG (57.89%) for H. pylori IgG (p > 0.05). A significant difference was found between AsAA (78.95%) and HCG (57.89%) for H.pylori IgG (p < 0.05) by ELISA and a significant difference was found only between AsAA (100%) and HCG (37.5%) for H. pylori IgG in the 45-55 age group by WB. A statistically significant difference was found between AAA and AsAA for VacA and CagA + VacA and CagA + VacA + UreA antigens and also a significant difference was found between AsAA and HCG for CagA + UreA antigens (p < 0.05). Finally, we suggest that H. pylori VacA has a more important role than CagA in the development of two aneurysms especially in ruptured AAA. New extended studies detecting H. pylori DNA are needed to detect the aetiopathogenesis between aneurysm types and H. pylori.     

Phytochemical Profiling and Biological Activity of Achillea sintenisii Hub.-Mor

Achillea (Asteraceae) species have been traditionally used for their different therapeutical properties. In this study, phytochemical composition of aerial parts of A. sintenisii which is endemic in Turkey was determined with Liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). To evaluate the wound healing potential, the cream formulation prepared from A. sintenisii was tested on the linear incision wound model in mice. In vitro enzyme inhibitory activity tests were performed on elastase, hyaluronidase, and collagenase. In the histopathological examination, angiogenesis and granulation tissue formation were significantly increased in A. sintenisii treatment groups compared to the negative control group. As a result of this study, it is thought that the enzyme inhibition and antioxidant activity of the plant may contribute to the wound healing process. According to LC/MS/MS analysis result, quinic acid (24.261 μg/mg extract) and chlorogenic acid (14.97 μg/mg extract) were identified as main constituents of the extract.     

Visfatin Levels in Subclinical Hypothyroidism

Alterations in thyroid function are associated with changes in body weight, metabolism, and low-grade inflammation abnormal thyroid function may be associated with disturbances in the production of adipokines also. Although there have been studies showing changes in visfatin levels in thyroid dysfunction, exact relationship between them was still unclear. Our aim was to evaluate serum concentrations of visfatin in patients with subclinical thyroid dysfunction before and after normalization of thyroid function tests. The study included 43 patients (mean age 50.1 ± 10.6 years) with subclinical hypothyroidism. Serum insulin, visfatin, TSH, free T4 (FT4) and free T3 (FT3) levels of subjects were analyzed. Visfatin levels were measured in all patients before starting therapy and after normalization of thyroid function. Serum visfatin levels of subclinical hypothyroid patients were 0.99 ± 0.45 and they were similar after normalization of thyroid function (p = 0.394). Serum visfatin levels were negatively correlated with FT4 levels before treatment (r = ?0.329 p < 0.05). There was no significant correlation between serum levels of visfatin and the serum levels of TSH and FT3. Serum visfatin levels did not correlate with insulin, fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels. In this study, it was shown visfatin levels did not change after replacement therapy in patients with subclinical hypothyroidism. Subclinical hypothyroid state may be an earlier stage regarding the changes of adipocytokines specifically the visfatin secretion as seen in overt hypothyroidism.     

The role of miRNAs as a predictor of multicentricity in breast cancer

Expression profiles of miRNAs are shown to be different in various cancers to regulate expression of mRNA or to have a role in inhibition of translation, thus it shows the possible effect in progression, invasion and metastasis of breast cancer cells. The effect of breast conserving treatment in local recurrence and survival rates for the patients who have multicentric breast cancer is still controversial. In our study, we intended to evaluate the foresight of 84 miRNAs which are identified in breast cancer for having differentiated expressions. Thirty-one patients with unifocal and 26 patients with multicentric breast cancer were included in this study. These tissue samples of both malignant and normal breast tissues were kept in RNA later solution at ??80 °C. Eighty-four miRNAs were studied with miScript miRNA PCR Array Human Breast Cancer kit. Fold change, cut off value was accepted as four. In unifocal group, there were 13 upregulated and five downregulated miRNAs and in multicentric group, there were three upregulated and seven downregulated miRNAs. To reach better results for breast cancer diagnosis and treatment, it is important to enlighten tumor biology, and pay attention to target and individual therapy. Thus, miRNAs have potential role in identifying tumor characteristics in supporting diagnosis and resulting with better evaluated disease for better treatment results with individual strategies.

     

Protective effect of melatonin against oxidative stress on adhesion formation in the rat cecum and uterine horn model

This experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) and the effect of melatonin on these metabolites in a postoperative intraperitoneal adhesion formation model in rats. Thirty adult female Wistar albino rats were subjected to standardized lesions by cecal and uterine horn abrasion and were randomly divided into three groups. Control rats were treated with 5% ethanol. Melatonin treated rats received 4 mg/kg melatonin before closure and for 10 consecutive days intraperitoneally after surgery. Rats in the sham operation group underwent a surgical procedure similar to the other groups however the peritoneal abrasion was not performed. On postoperative day 10 relaparatomy was performed. After the assessment of the adhesions, the rats in each group were sacrificed and peritoneal tissues were harvested to determine the tissue levels of MDA, GSH and NO activity. Adhesion formation scores in the melatonin group were significantly lower than that of control and sham group (p<0.01 and p<0.02, respectively). Tissue levels of MDA and NO were significantly lower in the melatonin treated rats when compared with control and sham groups. The levels of GSH in the melatonin treated rats were significantly higher than those of control and sham groups (p<0.01). The results demonstrate that in this experimental model, intraperitoneal administration of melatonin decreases the extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH levels.     

ERK5 activates NF-kappaB in leukemic T cells and is essential for their growth in vivo

MAPK cascades play a central role in the cellular response to the environment. The pathway involving the MAPK ERK5 mediates growth factor- and stress-induced intracellular signaling that controls proliferation or survival depending upon the cell context. In this study, we show that reducing ERK5 levels with a specific small hairpin RNA 5 (shERK5) reduced cell viability, sensitized cells to death receptor-induced apoptosis, and blocked the palliative effects of phorbol ester in anti-Fas Ab-treated cells. shERK5 decreased nuclear accumulation of the NF-kappaB p65 subunit, and conversely, ectopic activation of ERK5 led to constitutive nuclear localization of p65 and increased its ability to trans activate specific reporter genes. Finally, the T lymphoma cell line EL-4, upon expression of shERK5, proliferated in vitro, but failed to induce s.c. tumors in mice. Our results suggest that ERK5 is essential for survival of leukemic T cells in vivo, and thus represents a promising target for therapeutic intervention in this type of malignancy.