Ayşegül Görür

Comparison of plasma MicroRNA levels in drug naive, first episode depressed patients and healthy controls

Major depression is the most common psychiatric disorder. The diagnosis of depression depends on a patients subjective complaints, and the nature of the heterogeneous disorder. Thus, there is no known biomarker for depression to date. Previous research has indicated that microRNAs are dysregulated in bipolar disorder and schizophrenia. We aimed to investigate microRNA dysregulation in plasma samples of patients with major depression. Venous blood samples of 50 depressed patients and 41 healthy controls were collected and the quantification of microRNAs was established using qRT-PCR. We found miR-320a significantly downregulated and miR-451a significantly upregulated in depressed patients. We also found miR-17-5p and miR-223-3p upregulated, but not as significantly as miR-451a. Merging our results with previous published data shows that the blood miR-320 family may be a potential microRNA family dysregulated in major depression. Research should be performed on miR-320-related pathways and their relationship to depression. Additionally, miR-451a could serve as a candidate biomarker for depression based on the acting mechanism of ketamine. Studies targeting miR-451a levels before and after treatment could be helpful.

Circulating microRNA expression profiles in ovarian cancer

Abstract MicroRNA (miRNA) is an abundant class of small non-coding RNAs that act as gene regulators. Recent studies have suggested that miRNA deregulation is associated with the initiation and progression of human cancer. However, information about ovarian cancer-related miRNA is mostly limited to tissue miRNA. The aim of this study was to find specific profiles of plasma-derived miRNAs of ovarian cancer. In this present study, the expression profiles of 740 miRNAs in plasma from 18 patients and 24 healthy women subjects were evaluated using microfluidic based multiplex qRT-PCR. Our results demonstrated that expression levels of eight miRNAs were significantly upregulated in patients with ovarian cancer when compared with a control group (p < 0.05). Expression levels of four miRNAs were found significantly downregulated in patients with ovarian cancer (p < 0.05). In addition, 10 miRNAs were expressed only in the ovarian cancer group and miR-138-5p of these miRNAs is ovarian specific. In conclusion, our study suggests that detecting these ovarian cancer specific miRNAs in plasma might serve as novel non-invasive biomarkers for ovarian cancer.

BMI and levels of zinc, copper in hair, serum and urine of Turkish male patients with androgenetic alopecia

OBJECTIVE Male pattern androgenetic alopecia is characterized by progressive hair loss from the scalp. It is known that imbalances of some trace elements play a role in the pathomechanism of many forms of alopecia. The aim of this study was to evaluate the levels of zinc and copper in hair, serum and urine samples of Turkish males with male pattern androgenetic alopecia and to compare with healthy controls. MATERIAL AND METHODS 116 males with male pattern androgenetic alopecia and 100 controls were involved in this study. RESULTS Levels of zinc and copper in hair were decreased significantly in the patients (p<0.05), although zinc and copper levels of serum and urine were not different between patients and controls (p>0.05). Body mass index of patients were higher than control group. In addition, in the group with body mass index of 25 and lower zinc level in hair and urine, copper level in serum were significantly higher (p<0.05). Body mass index was negatively correlated with hair zinc levels. CONCLUSION We thought that decreased zinc and copper levels in hair may play a role in the etiology of male pattern androgenetic alopecia. In addition, obesity by making changes in the balance of the trace elements in hair, serum and urine may play a role in male pattern androgenetic alopecia. Hence, assessing the levels of trace elements in hair of male pattern androgenetic alopecia patients may be more valuable compared to serum and urine for treatment planning.

Contribution of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway to ischemia/reperfusion-induced oxidative/nitrosative stress and inflammation leading to distant and target organ injury in rats.

The small G protein RhoA and its downstream effector Rho-kinase play an important role in various physiopathological processes including ischemia/reperfusion (I/R) injury. Reactive oxygen and nitrogen species produced by iNOS and NADPH oxidase are important mediators of inflammation and organ injury following an initial localized I/R event. The aim of this study was to determine whether RhoA/Rho-kinase signaling pathway increases the expression and activity of MEK1, ERK1/2, iNOS, gp91(phox), and p47(phox), and peroxynitrite formation which result in oxidative/nitrosative stress and inflammation leading to hindlimb I/R-induced injury in kidney as a distant organ and gastrocnemius muscle as a target organ. I/R-induced distant and target organ injury was performed by using the rat hindlimb tourniquet model. I/R caused an increase in the expression and/or activity of RhoA, MEK1, ERK1/2, iNOS, gp91(phox), p47(phox), and 3-nitrotyrosine and nitrotyrosine levels in the tissues. Although Rho-kinase activity was increased by I/R in the kidney, its activity was decreased in the muscle. Serum and tissue MDA levels and MPO activity were increased following I/R. I/R also caused an increase in SOD and catalase activities associated with decreased GSH levels in the tissues. Y-27632, a selective Rho-kinase inhibitor, (100µg/kg, i.p.; 1h before reperfusion) prevented the I/R-induced changes except Rho-kinase activity in the muscle. These results suggest that activation of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway associated with oxidative/nitrosative stress and inflammation contributes to hindlimb I/R-induced distant organ injury in rats. It also seems that hindlimb I/R induces target organ injury via upregulation of RhoA/MEK1/ERK1/2/iNOS pathway associated with decreased Rho-kinase activity.

Activation of mTOR/IκB-α/NF-κB pathway contributes to LPS-induced hypotension and inflammation in rats

ABSTRACT Mammalian target of rapamycin (mTOR), a serine/threonine kinase plays an important role in various pathophysiological processes including cancer, metabolic diseases, and inflammation. Although mTOR participates in Toll‐like receptor 4 signalling in different cell types, the role of this enzyme in sepsis pathogenesis and its effects on hypotension and inflammation in endotoxemic rats remains unclear. In this study we investigated the effects of mTOR inhibition on lipopolysaccharide (LPS)‐induced changes on expressions and/or activities of ribosomal protein S6 (rpS6), an mTOR substrate, nuclear factor‐&kgr;B (NF‐&kgr;B) p65, inhibitor &kgr;B (I&kgr;B)‐&agr;, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)−2 with production of nitric oxide, peroxynitrite, prostacyclin, and tumor necrosis factor (TNF)‐&agr; and activity of myeloperoxidase (MPO), which results in hypotension and inflammation. Injection of LPS (10 mg/kg, i.p.) to male Wistar rats decreased blood pressure and increased heart rate that were associated with elevated nitrotyrosine, 6‐keto‐PGF1&agr;, and TNF‐&agr; levels and MPO activity, and increased expressions and/or activities of rpS6, NF‐&kgr;B p65, iNOS, and COX‐2 and decreased expression of I&kgr;B‐&agr; in renal, cardiac, and vascular tissues. LPS also increased serum and tissue nitrite levels. Rapamycin (1 mg/kg, i.p.) given one h after injection of LPS reversed these effects of LPS. These data suggest that the activation of mTOR/I&kgr;B‐&agr;/NF‐&kgr;B pathway associated with vasodilator and proinflammatory mediator formation contributes to LPS‐induced hypotension and inflammation.

Affirmative Effects of Iloprost on Apoptosis during Ischemia-Reperfusion Injury in Kidney as a Distant Organ

Abstract Objective: Apoptosis and its regulatory mechanisms take part in renal ischemia–reperfusion (I/R) injury which can result in acute renal failure and the inhibition of the caspase is considered as a new therapeutic strategy. In this context, we investigated the antiapoptotic and cytoprotective effects of iloprost, a prostacyclin analog, in kidney as a distant organ. Methods: Wistar albino rats were randomized into five groups (n = 12 in each) as sham, ischemia, I/R, iloprost (10 μg kg−1), and I/R + iloprost (10 μg kg−1). A 4 h reperfusion procedure was carried out after 4 h of ischemia. Caspase-8 was evaluated for death receptor-induced pathways, whereas caspase-9 was evaluated for mitochondria-dependent pathways and caspase-3 was investigated for overall apoptosis. Superoxide dismutase (SOD) enzyme activity and nitrite content as an indicator of nitric oxide (NO) production were also analyzed in kidney tissues. Results: Caspases-3, -8, and -9 were all significantly elevated in both ischemia and I/R groups compared to the sham group; however, treatment with iloprost reduced caspases-3, -8, and -9. SOD enzyme activity was attenuated by iloprost when compared to ischemic rats. The different effects of NO were found which change according to the present situation in ischemia, I/R, and treatment with iloprost. Conclusions: These findings suggested that iloprost prevents apoptosis in both receptor-induced and mitochondria-dependent pathways in renal I/R injury and it may be considered as a cytoprotective agent for apoptosis. Understanding the efficiency of iloprost on the pathways for cell death may lead to an opportunity in the therapeutic approach for renal I/R injury.

Glutathione S-transferase GSTM 1, null genotype may be associated with susceptibility to age-related cataract.

BACKGROUND Age-related cataract (ARC) is the leading cause of visual disability and reversible blindness all over the world. The different expressions of GST isozymes among animals may explain the variations in the cataract formation caused by oxidative stress. OBJECTIVES In this study, we evaluated the distribution of GST gene polymorphisms in ARC patients and the possible associations between the presence of ARC and GST gene polymorphisms. MATERIAL AND METHODS The epidemiological data was collected by a standard questionnaire and blood samples were obtained from 130 ARC patients and 159 healthy controls. Data about smoking habits of the groups was recorded. Real-time polymerase chain reaction-based methods were used to detect genetic polymorphisms. RESULTS The GSTM 1 null genotype was found to carry an increased risk for developing ARC (OR: 1.84, 95% CI: 1.13-2.99). The frequency of the GSTT 1 null genotype was not significantly different among the ARC patients and the controls (OR: 1.0, 95% CI: 0.64-1.6). The GSTP 1 Val/Val genotype was also not significantly different among the ARC patients and control groups (OR: 1.06, 95% CI: 0.50-2.23). GSTM 1 null genotype was highly frequent in non-smokers (OR: 3.25, 95% CI: 1.66-6.35) and moderately frequent in smokers (OR: 2.50, 95% CI: 1.28-4.86). Also, carrying the combined genotypes of GSTM 1 null, GSTT 1 and GSTP 1 105-Val allele was seen to have an increased risk of developing ARC (OR: 2.91, 95% CI: 1.31-6.44). CONCLUSIONS This data may provide evidence that GSTM 1 gene polymorphisms may be associated with genetic susceptibility to develop ARC. Larger studies are warranted to verify these findings.

Comparison of microRNA profiles between benign and malignant salivary gland tumors in tissue, blood and saliva samples: a prospective, case-control study

INTRODUCTION Salivary gland tumors (SGTs) are rare head and neck malignancies consisting of a spectrum of tumors with different biological behaviors. OBJECTIVE In this study we aimed to find out differential expression of microRNA profiles between benign and malignant SGTs. METHODS We investigated the possible role of 95 microRNAs in the 20 patients with salivary gland tumors with comparison of 17 patients without malignancy or salivary gland diseases. Sixteen of the tumors were benign (seven pleomorphic adenomas, nine Warthin tumors), four of them were malignant (two squamous cell carcinomas, one high grade mucoepidermoid carcinoma, one adenocarcinoma). Serum and saliva samples were collected from both patients and control group. Tissue samples of tumor masses were also collected from patient group. RESULTS Among studied microRNAs miR-21, miR-23a, miR-27a, miR-223, miR-125b, miR-126, miR-146a, miR-30e were down regulated in the benign group compared to control group in the serum samples (p-values are 0.04, 0.00005, 0.00005, 0.0022, 0.031, 0.00008, 0.044, and 0.0007, respectively). When tissue samples were studied miR-21, miR-31, miR-199a-5p, miR-146b, miR-345 were up-regulated in the malignant group compared to benign group (p values are 0.006, 0.02, 0.013, 0.013, 0.041, respectively). miR-30e showed statistically significant up-regulation in malignant tumor groups plasma samples compared to benign group (p=0.034). There was no statistically significant difference in saliva samples between groups. CONCLUSION Our results showed that different microRNAs may play role in salivary tumor pathogenesis according to biological behavior. Although there was no difference in saliva samples between groups, according to tissue and serum samples miR-21 and 30e may have an important role; since they were down-regulated in benign tumors whereas up-regulated in malignant ones.

Apoptotic and Anti-Angiogenic Effects of Benzimidazole Compounds: Relationship with Oxidative Stress Mediated Ischemia/Reperfusion Injury in Rat Hind Limb

Ischemia/reperfusion (I/R)-induced injury is a pathophysiological process consisting of a complex cascade characterized by an increase in reactive oxygen species production, pro-inflammatory cytokine release, and activated endothelial cells leading to cell damage and death. The aim of this study was to investigate effects of substituted 2-benzylbenzimidazole derivatives, 2-(3-methoxybenzyl)benzimidazole (BB3) and 2-(4-methoxybenzyl)benzimidazole (BB4), on I/R-induced changes in the markers of oxidative stress, apoptosis, and angiogenesis in rats. BB3 and BB4 were synthesized with microwave irradiation and conventional Phillips methods. I/R was performed by occlusion of femoral artery. Catalase activity and reduced glutathione (GSH) levels as well as caspase-3, -8, and -9 activities were measured in muscle tissues as an index for oxidative stress and apoptosis, respectively. Vascular endothelial growth factor (VEGF) levels as an index for angiogenesis were also measured in the muscle tissues and sera. I/R decreased GSH levels, increased catalase activity and VEGF levels, and did not change caspase-3, -8, and -9 activities compared to control groups. BB3 and BB4 caused a further decrease in GSH levels and increased caspase-3, -8, and -9 activities in I/R group. These compounds caused a further increase in catalase activity and prevented the increase in VEGF levels induced by I/R. These data suggest that BB3 and BB4 exhibit apoptotic and anti-angiogenic activity with pro-oxidative effects resulting in oxidative stress in pathophysiological process of I/R-induced hind limb injury in rats.

Evaluation of the plasma microRNA levels in stage 3 premature retinopathy with plus disease: preliminary study

PurposeIn the present study, we aimed to investigate the changes in plasma microRNA (miRNA) levels in premature infants diagnosed with premature retinopathy (ROP).Patients and methodsIn order to investigate the relationship of miRNAs with ROP, 13 premature infants admitted to Mersin University, Medical School, Department of Ophthalmology and diagnosed with ROP stage 3 with plus disease between January 2014–January 2015 were included in the study. Control group consisted of 15 premature infants with no ROP. The plasma miRNA levels were evaluated using high-throughput quantitative real-time PCR.ResultsThe results of study demonstrated that the expression level of miR-23a and miR-200b-3p was significantly upregulated in patients with ROP when compared with the control group (P<0.05). The expression level of miR-27b-3p and miR-214-3p was significantly downregulated in patients (P<0.05). In addition, expression of 17 miRNA (miR-410-3p, miR-17-5p, miR-451a, miR-31-5p, miR-132-3p, miR-183-5p, miR-184, miR-222-3p, miR-296-5p, miR-200a-3p, miR-328-3p,miR-96-5p, miR-199a-5p, miR-99a-5p, miR-106a-5p, miR-125b-5p, miR-155-5p) had upregulated or downregulated, but not statistically significantly different when compared with the control group.ConclusionsOur results suggest that plasma miRNA levels may alter in ROP and, some miRNAs might have an effect in the physiopathology of this disease. These molecules may have an important therapeutic role in patients who are unresponsive to anti-vascular endothelial growth factor therapy. However, further studies must be conducted for possible effects of miRNAs in vascular disorders of eye such as ROP. Moreover to define the relationship of these molecules with the disease more clearly, a multicenter study including more patients is necessary.