Setenay Oner

Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools

Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs’ regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.

Effects of Doxycycline on Renal Ischemia Reperfusion Injury Induced by Abdominal Compartment Syndrome

BACKGROUND The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment syndrome (ACS). MATERIALS AND METHODS Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no manipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1 cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1β, IL-6, TNF-α, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. RESULTS Creatinine, MDA, IL-1β, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1 hour after decompression. However, there remained no difference between groups at 24h, except IL-1β, which was decreased to even lower values. TNF-α and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expression of bcl-2 was significantly less in the groups in which doxycycline was administered. CONCLUSION Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.

Comparison of Semiparametric, Parametric, and Nonparametric ROC Analysis for Continuous Diagnostic Tests Using a Simulation Study and Acute Coronary Syndrome Data

We aimed to compare the performance of three different individual ROC methods (one from each of the broad categories of parametric, nonparametric and semiparametric analysis) for assessing continuous diagnostic tests: the binormal method as a parametric method, an empirical approach as a nonparametric method, and a semiparametric method using generalized linear models (GLM). We performed a simulation study with various sample sizes under normal, skewed, and monotone distributions. In the simulations, we used estimates of the ROC curve parameters a and b, estimates of the area under the curve (AUC), the standard errors and root mean square errors (RMSEs) of these estimates, and the 95% AUC confidence intervals for comparison. The three methodologies were also applied to an acute coronary syndrome dataset in which serum myoglobin levels were used as a biomarker for detecting acute coronary syndrome. The simulation and application studies suggest that the semiparametric ROC analysis using GLM is a reliable method when the distributions of the diagnostic test results are skewed and that it provides a smooth ROC curve for obtaining a unique cutoff value. A sample size of 50 is sufficient for applying the semiparametric ROC method.

Effects of placebo-controlled continuous and pulsed ultrasound treatments on carpal tunnel syndrome: a randomized trial

OBJECTIVE: The aim of this placebo-controlled study was to evaluate the effects of pulsed and continuous ultrasound treatments combined with splint therapy on patients with mild and moderate idiopathic carpal tunnel syndrome. METHODS: The study included 46 carpal tunnel syndrome patients who were randomly divided into 3 groups. The first group (n = 15) received a 0 W/cm2 ultrasound treatment (placebo); the second group (n = 16) received a 1.0 W/cm2 continuous ultrasound treatment and the third group (n = 15) received a 1.0 W/cm2 1:4 pulsed ultrasound treatment 5 days a week for a total of 15 sessions. All patients also wore night splints during treatment period. Pre-treatment and post-treatment Visual Analogue Scale, Symptom Severity Scale and Functional Status Scale scores, median nerve motor conduction velocity and distal latency and sensory conduction velocities of the median nerve in the 2nd finger and palm were compared. Clinicaltrials.gov: NCT02054247. RESULTS: There were significant improvements in all groups in terms of the post-treatment Functional Status Scale score (p<0.05 for all groups), Symptom Severity Scale score (first group: p<0.05, second group: p<0.01, third group: p<0.001) and Visual Analogue Scale score (first and third groups: p<0.01, second group: p<0.001). Sensory conduction velocities improved in the second and third groups (p<0.01). Distal latency in the 2nd finger showed improvement only in the third group (p<0.01) and action potential latency in the palm improved only in the second group (p<0.05). CONCLUSION: The results of this study suggest that splinting therapy combined with placebo and pulsed or continuous ultrasound have similar effects on clinical improvement. Patients treated with continuous and pulsed ultrasound showed electrophysiological improvement; however, the results were not superior to those of the placebo.

Monitoring and assessment of airborne Cladosporium Link and Alternaria Nées spores in Sivrihisar (Eskisehir), Turkey

The spores of Cladosporium spp. and Alternaria spp., commonly described as the most allergenic spores, were collected by means of Durham gravimetric sampler from the Sivrihisar (Eskisehir) atmosphere throughout 2005 to 2006. The weekly variations in spores/cm2 of Cladosporium and Alternaria were recorded. During this period, a total of 6,198 spores belonging to Cladosporium spp. and Alternaria spp. were recorded. Of these spores, 2,969 were identified in 2005 and 3,229 in 2006. While 69.55% of the total spores were those of Cladosporium spp., 30.45% were Alternaria spp. Relationships between airborne fungal spore presence and weather conditions were examined statistically. A Shapiro–Wilk test revealed that the airborne spores of Cladosporium spp. and Alternaria spp. had a normal distribution. Following this, Chi-square test, t test and Pearson correlation analysis were performed. The effects of temperature and relative humidity on the spore numbers of Cladosporium spp. and Alternaria spp. were significant according to the month in which they were collected (p < 0.01). The spore concentrations of each species reached to their highest levels in June 2006.

Preventive Effects of Ginkgo biloba Extract on Ischemia-Reperfusion Injury in Rat Bladder

Aims: The aim of this experimental study was to evaluate the effects of Ginkgo biloba (EGb 761) on ischemia-reperfusion (I-R) injury in the rat bladder. Methods: A bladder I-R injury was induced by abdominal aorta occlusion by ischemia for 30 min, followed by 45 min reperfusion in rats. The rats were divided into four groups of 7 rats each; the control, I-R, and I-R groups were pretreated intraperitoneally with 50 or 100 mg/kg G. biloba 60 min before ischemia induction. Contractile responses to carbachol through isolated organ bath studies were recorded, histological sections were evaluated by light microscopy, and TUNEL staining was performed for the evaluation of apoptosis. Results: In the I-R group, the contractile responses of the bladder strips were lower than those of the control group (p < 0.01–0.001) and were restored by pretreatment with 100 mg/kg G. biloba (p < 0.05–0.001). Decreased polymorphonuclear leukocyte infiltration was detected in the G. biloba pretreatment groups when compared to the I-R group during histological evaluation. The ratio of TUNEL-positive nuclei was 1.84% in the I-R group, whereas it was decreased in both of the G. biloba pretreatment groups (p < 0.01, p < 0.01). Conclusion: Our data indicated that G. biloba has a preventive effect on I-R injury in rat urinary bladder.

Inhalation Therapy of Calcitonin Relieves Osteoarthritis of the Knee

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1β, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.

Sex-related differences in methods of and reasons for suicide in Turkey between 1990 and 2010

Objective To analyse suicides occurring in Turkey between 1990 and 2010 according to sex, age, reason and method. Methods Data concerning suicides occurring in Turkey between 1990 and 2010 were obtained from annual records published by the Turkish Statistical Institute. Data were analysed according to sex, age, reason for suicide and suicide method. Results The crude suicide rate was 2.42 per 100 000 population in 1990 and 4.02 per 100 000 population in 2010. The highest number of suicides was seen in those aged 15–24 years. In this age group, the number of suicides in females was significantly higher than in males. The most common suicide method in Turkey was hanging. Men used firearms more frequently than women. All the reasons for suicide occurred in a higher number of males than females; however, the difference between males and females was more significant for economic problems, relationship problems and educational failure. The leading reason for suicide in females was relationship problems. Conclusion Detecting population subgroups with a high suicide risk and obtaining regional demographic data are of great importance for future studies on suicide prevention.

Effects of single and combined gabapentin use in elevated plus maze and forced swimming tests.

Background Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders. Objectives We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats. Material and Methods Female Spraque–Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively. Results It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them. Conclusions These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model

BACKGROUND Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema. OBJECTIVE The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS. METHODS Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and β-cell lymphoma 2 (βcl-2) expression were assessed immunohistochemically. RESULTS Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1β, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of βcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively). CONCLUSION Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.