Publications by authors named "Yuksel Yildiz"

11 Publications

  • Page 1 of 1

Effect of experimentally induced hypothyroidism during gestation period on activity dependent neurotrophic factor (ADNF) in newborn rat brain tissue.

Horm Mol Biol Clin Investig 2018 Sep 26;36(3). Epub 2018 Sep 26.

Izmir Katip Celebi University, Faculty of Medicine, Department of Family Medicine, Izmir, Turkey, Phone: +90.505.6487644.

Purpose The aim of the study was to evaluate the effects of prenatal hypothyroidism on neonatal rats by the way of activity-dependent neuroprotective factor (ADNF) expression. Methods Twenty-one Wistar albino neonatal rats were divided into two subgroups; a control group and neonatal rats with experimental maternal hypothyroidism. Hypothyroidism was induced by using propylthiouracil (PTU). Neonatal rats obtained PTU from breast milk continuously for 1 week after birth. The rats from the control group were fed only normal feed and water. After birth, body weight and blood thyroid hormone levels were tested. Glial fibrillary acidic protein (GFAP), Slug, Numb, Notch-1 and ADNF antibodies were used for immunohistochemical analysis. Real-time polymerase chain reaction (RT-PCR) and Western blotting analyses were used to evaluate ADNF gene expression levels from 1-week-old rat's brain. Results There was no difference between the two groups for birth weights. The thyroxine (T4) level from the experimental group was <0.4 ng/mL, and it was 0.8 ng/mL for the control group. It was shown that, the results from the experimental group samples had significantly lower ADNF mRNA levels than control group (p < 0.05). The increase from GFAP and Numb expression and decrease from Slug expression were shown in the experimental group. Local differences were identified for ADNF and a decrease was shown in both sides of brain. There was no difference for Notch-1 expression for both groups. Conclusion In this study, decreasing ADNF expression might contribute to developing neurological problems in congenital hypothyroidism.
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http://dx.doi.org/10.1515/hmbci-2017-0069DOI Listing
September 2018

Mapping the STK4/Hippo signaling network in prostate cancer cell.

PLoS One 2017 7;12(9):e0184590. Epub 2017 Sep 7.

Department of Biological Sciences, the Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, Georgia, United States of America.

Dysregulation of MST1/STK4, a key kinase component of the Hippo-YAP pathway, is linked to the etiology of many cancers with poor prognosis. However, how STK4 restricts the emergence of aggressive cancer remains elusive. Here, we investigated the effects of STK4, primarily localized in the cytoplasm, lipid raft, and nucleus, on cell growth and gene expression in aggressive prostate cancer. We demonstrated that lipid raft and nuclear STK4 had superior suppressive effects on cell growth in vitro and in vivo compared with cytoplasmic STK4. Using RNA sequencing and bioinformatics analysis, we identified several differentially expressed (DE) genes that responded to ectopic STK4 in all three subcellular compartments. We noted that the number of DE genes observed in lipid raft and nuclear STK4 cells were much greater than cytoplasmic STK4. Our functional annotation clustering showed that these DE genes were commonly associated with oncogenic pathways such as AR, PI3K/AKT, BMP/SMAD, GPCR, WNT, and RAS as well as unique pathways such as JAK/STAT, which emerged only in nuclear STK4 cells. These findings indicate that MST1/STK4/Hippo signaling restricts aggressive tumor cell growth by intersecting with multiple molecular pathways, suggesting that targeting of the STK4/Hippo pathway may have important therapeutic implications for cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184590PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589252PMC
October 2017

The protective effect of tadalafil on IMA (ischemia modified albumin) levels in experimental renal ischemia-reperfusion injury.

Int J Clin Exp Med 2015 15;8(9):15766-72. Epub 2015 Sep 15.

Department of Urology, School of Medicine, Adnan Menderes University Aydin, Turkey.

Introduction: To investigate the effect of the tadalafil in experimental renal I/R injury and to evaluate these changes with IMA (nonspesific early biomarker of ischemia), NO and MDA levels.

Materials And Methods: Twenty four female Wistar rats were randomly divided into 3 groups (n=8): Group I, sham; Group II, 60 min I/R; Group III, 60 min I/R plus tadalafil. Tadalafil was administered via an orogastric tube (10 mg/kg) 24 h prior to the procedure. After ischemia of the left kidney and 1 h of reperfusion, blood samples were obtained, and the kidney was removed.

Results: Statistically significant histopathologic changes were exist between groups, with the most severe injury was determined in group II in comparison to the others (X(2)=21,803, P=0.000). Also mean serum IMA levels were higher in group II, but not statistically significant (19.83±7.81 U/ml, 22.26±7.14 U/ml and 19.82±7.77 U/ml, P=0.613). In addition, NO values were lower in I/R groups (P=0.049). There were no differences among the groups in terms of MDA.

Conclusions: IMA may be used as a nonselective biomarker for IR injury before the occurrence of necrosis. Decreased IMA levels may indicate the nephroprotective effect of tadalafil in renal IR injury.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658963PMC
December 2015

Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats.

Recent Pat Endocr Metab Immune Drug Discov 2015 ;9(2):134-40

Department of Physiology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey 09100.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997944PMC
http://dx.doi.org/10.2174/1872214809666150806105737DOI Listing
October 2016

Protective effects of citicoline on TNBS-induced experimental colitis in rats.

Int J Clin Exp Med 2014 15;7(4):989-97. Epub 2014 Apr 15.

Department of Biophysics, Adnan Menderes University Aydin, Turkey.

The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057851PMC
June 2014

Protective effects of leflunomide on intestinal ischemia-reperfusion injury: leflunomide against intestinal ischemia-reperfusion.

Dig Dis Sci 2010 Feb 20;55(2):245-52. Epub 2009 Feb 20.

Department of Physiology, Faculty of Medicine, Adnan Menderes University, Aydin 09100, Turkey.

Aim: The aim of this study was to investigate the possible protective effects of leflunomide, which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats.

Materials And Methods: Forty female Wistar albino rats were divided into six groups: control (n = 5), drug control (n = 7), sham operated (n = 7), IR alone (n = 7), IR plus vehicle (IR + vehicle, n = 7) and IR plus 20 mg/kg leflunomide (IR + Leflunomide, n = 7). While rats were pretreated intragastrically with leflunomide (20 mg/kg) and vehicle in three doses prior to the experiment, respectively, in the IR + Leflunomide and IR + vehicle groups, no additional application was done in the IR alone group. Intestines were exteriorized, and the superior mesenteric artery was occluded for 45 min ischemia, and then the clamp was removed for 120 min reperfusion. After the experiment, the intestines were removed for biochemical and histological examinations. Additionally, blood samples were taken for measurements of antioxidant parameters.

Results: The intestinal IR significantly increased the MDA level and MPO activity; however, treatment with leflunomide reversed those findings (P < 0.05). The CAT activity of the IR + Leflunomide group was significantly higher than in the IR groups (P < 0.05). The SOD activity was increased in the intestinal IR group, and leflunomide treatment reversed that, too (P <0.05). The light microscopic findings showed that IR caused mucosal necrosis and leflunomide treatment reduced the morphological alterations associated with IR (P < 0.05).

Conclusion: Intestinal IR injury may be reversed by the anti-inflammatory and antioxidant actions of leflunomide.
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http://dx.doi.org/10.1007/s10620-009-0737-0DOI Listing
February 2010

Protective effects of caffeic acid phenethyl ester on intestinal ischemia-reperfusion injury.

Dig Dis Sci 2009 Apr 6;54(4):738-44. Epub 2008 Aug 6.

Department of Physiology, Medical Faculty, Adnan Menderes University, Aydin, 09100, Turkey.

Aim: Intestinal ischemia reperfusion (IR) causes tissue injury in two ways, starting a pro-inflammatory cascade and oxidative stress. The aim of this study was to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE), which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats.

Materials And Methods: Forty male Wistar-Albino rats were divided into five groups: Sham, IR, IR plus ethanol (vehicle), IR plus 10 mg/kg (IR + 10CAPE), and 30 mg/kg CAPE (IR + 30CAPE) at the 30-min ischemic period. Intestines were exteriorized and the superior mesenteric artery was occluded for 45-min ischemia and then the clamp was removed for 120-min reperfusion. After the experiment, the intestines were removed for biochemical and light microscopic examinations. Additionally, blood samples were taken for plasma TNF-alpha measurement.

Results: The TBARS levels of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). Both CAPE treatments decreased TBARS levels in comparison with the IR group (P < 0.05). In both CAPE-treated groups, while the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were increased compared to all other groups, which was similarly the case for the CAT activity compared to the Sham and IR + Ethanol groups (P < 0.05). There were no significant differences between GSH levels of all study groups. The TNF-alpha levels of the IR and IR + Ethanol groups were non-significantly increased compared to the Sham group (P > 0.05). The TNF-alpha levels of 10 and 30 mg/kg CAPE groups were non-significantly decreased compared to the IR group (P > 0.05). The tissue MPO activities of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). The MPO activities of the IR + 10CAPE and IR + 30CAPE groups were not significantly different from the Sham group (P > 0.05). There was necrosis of mucosa in the IR and IR + Ethanol groups in light microscopic evaluations. Those changes were significantly reversed by 30 mg/kg CAPE treatment.

Conclusion: The intestinal IR injury may be reversed by anti-inflammatory and antioxidant actions of the CAPE. However, 30 mg/kg CAPE treatment may be more efficient in preventing intestinal IR injury in rats.
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http://dx.doi.org/10.1007/s10620-008-0405-9DOI Listing
April 2009

Effects of tamoxifen on myocardial ischemia-reperfusion injury model in ovariectomized rats.

Mol Cell Biochem 2008 Jan 3;308(1-2):227-35. Epub 2007 Nov 3.

Department of Physiology, Medical Faculty, Adnan Menderes University, Aydin 09100, Turkey.

The purpose of this study is to examine the antiarrhythmic and antioxidant effects of tamoxifen, one of the selective estrogen modulators, in ovariectomized rats subjected to myocardial ischemia-reperfusion (I/R) injury. A month after ovariectomy, rats were divided into four groups: (I) ovariectomized controls without any treatment, (II) ovariectomized rats treated with vehicle dimethylsulfoxide (DMSO), (III)-(IV) ovariectomized rats treated with tamoxifen 1 or 10 mg/kg,sc daily for 14 days. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. The blood pressure (BP), heart rate (HR), electrocardiography (ECG) was recorded before and during the ischemia-reperfusion period. The blood levels of malondialdehyde (MDA), creatine kinase (CK), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and catalase (CAT) were measured after the rats were killed. Tamoxifen reduced the incidence of ventricular tachycardia (VT) on ischemia and reperfusion as well as the incidence and duration of reversible ventricular fibrillation (VF) on reperfusion. I/R injury caused a significant fall in GSH, GSH-Px as well as an increase in MDA and CK levels in the control group when compared to tamoxifen treated groups. The changes in levels of CAT and GR were however, not significant. In conclusion, our findings suggest that tamoxifen has cardioprotective effects against I/R injury in rats, likely its antioxidant properties.
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http://dx.doi.org/10.1007/s11010-007-9633-0DOI Listing
January 2008

The effects of caffeic acid phenethyl ester (CAPE) on TNBS-induced colitis in ovariectomized rats.

Dig Dis Sci 2008 Jun;53(6):1609-17

Department of Physiology, Medical Faculty, Adnan Menderes University, Aydin 09100, Turkey.

Aim: The aim of this investigation was to examine the effects of caffeic acid phenethyl ester (CAPE) on the development of colitis and antioxidant parameters in bilateral ovariectomized rats subjected to trinitrobenzene sulfonic acid (TNBS)-induced colitis.

Materials And Methods: Twenty-one Wistar Albino ovariectomized female rats were divided into four subgroups (n = 5 or 6) (colitis control, vehicle control, CAPE 10 and 30 mg/kg, respectively). Colitis was induced using an enema of TNBS and ethanol, following which CAPE was administrated for 3 days to induce colitis and effect of CAPE was subsequently evaluated.

Results: Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and the vehicle-treated groups, whereas treatment with CAPE 10 and 30 mg/kg, respectively, caused a significant reduction in colon injury compared to that observed in rats of the TNBS-colitis and vehicle-treated groups. The histologies of both treatment groups were not significantly different. In terms of the biochemical analyses, myeloperoxidase levels in rats from the CAPE 10 and 30 mg/kg groups were significantly different from that of the colitis control rats; however, the levels of malondialdehyde (MDA), catalase and reduced glutathione (GSH) were only significantly different from the levels found colitis control rats in rats administered 10 mg/kg. The levels of MDA, GSH and SOD in rats given CAPE were also significantly different from those of rats in the vehicle control group. These results were consistent with histological findings.

Conclusion: CAPE may have a positive effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of CAPE may occur through antiinflammatory and antioxidant mechanisms.
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http://dx.doi.org/10.1007/s10620-007-0056-2DOI Listing
June 2008

Rapid assessment of anti-HIV siRNA efficacy using PCR-derived Pol III shRNA cassettes.

Mol Ther 2004 Sep;10(3):597-603

Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.

Identification of sequences within a target mRNA that are susceptible to potent siRNA knockdown often requires testing several independent siRNAs or shRNA expression cassettes. Using RNAi against HIV RNAs is further complicated by the length of the viral genome, the complexity of splicing patterns, and the propensity for genetic heterogeneity; consequently, it is most important to identify a number of siRNA targets that potently block viral replication. We previously described a facile PCR-based strategy for rapid synthesis of si/shRNA expression units and their testing in mammalian cells. Using this approach, which is rapid and inexpensive, it is possible to screen a number of potential RNAi targets in HIV to identify those that are most susceptible to RNAi. We report that shRNA expression cassettes constructed by PCR and cotransfected directly into mammalian cells with HIV proviral DNA express shRNAs that are inhibitory to HIV-1 replication. Our results also demonstrate that there is a wide range of efficacies among shRNAs targeting different sites throughout the HIV genome. By screening several different targets we were able to identify a sequence in a common tat/rev exon that is exquisitely sensitive to RNAi. Furthermore we relate the efficacies of our PCR product expressed shRNAs to the relative stabilities of the siRNA duplexes and the accessibilities of the target sites to antisense base pairing in cell extracts.
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http://dx.doi.org/10.1016/j.ymthe.2004.05.003DOI Listing
September 2004
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