137 results on '"Ulkan Kilic"'
Search Results
2. The therapeutic role of minocycline in Parkinson’s disease
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Seyda Cankaya, Baris Cankaya, Ulkan Kilic, Ertugrul Kilic, and Burak Yulug
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minocycline ,neurodegeneration ,neuroprotection ,Parkinson’s disease ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Minocycline, a semisynthetic tetracycline-derived antibiotic, has been shown to exert anti-apoptotic, anti-inflammatory, and antioxidant effects. Furthermore, there is rapidly growing evidence suggesting that minocycline may have some neuroprotective activity in various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson’s disease (PD), Huntington’s disease, and multiple sclerosis. In this perspective review, we summarize the preclinical and clinical findings suggesting the neuroprotective role of minocycline in PD.
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- 2019
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3. Particular phosphorylation of PI3K/Akt on Thr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice
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Ulkan Kilic, Ahmet Burak Caglayan, Mustafa Caglar Beker, Mehmet Yalcin Gunal, Berrak Caglayan, Esra Yalcin, Taha Kelestemur, Reyhan Zeynep Gundogdu, Burak Yulug, Bayram Yılmaz, Bilal Ersen Kerman, and Ertugrul Kilic
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Apart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI) in mice. However, it is not clear (i) whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii) how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI. Melatonin treatment reduced infarct volume, which was reversed by PI3K/Akt inhibition. However, PI3K/Akt inhibition did not inhibit melatonin's positive effect on brain swelling and IgG extravasation. Additionally, phosphorylation of mTOR, PTEN, AMPKα, PDK1 and RSK1 were increased, while phosphorylation of 4E-BP1, GSK-3α/β, S6 ribosomal protein were decreased in melatonin treated animals. In addition, melatonin decreased apoptosis through reduced p53 phosphorylation by the PI3K/Akt pathway. In conclusion, we demonstrated the activation profiles of PI3K/Akt signaling pathway components in the pathophysiological aspect of ischemic stroke and melatonin's neuroprotective activity. Our data suggest that Akt phosphorylation, preferably at the Thr308 site of the activation loop via PDK1 and PTEN, mediates melatonin's neuroprotective activity and increased Akt phosphorylation leads to reduced apoptosis. Keywords: PI3K/Akt signaling pathway, PI3K inhibition, Melatonin, Brain injury
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- 2017
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4. Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury
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Ilknur Keskin, M Yalcin Gunal, Nilufer Ayturk, Ulkan Kilic, Mehmet Ozansoy, and Ertugrul Kilic
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nerve regeneration ,neuroprotection ,traumatic brain injury ,cold-induced brain injury ,enoxaparin ,anti-oxidative ,apoptosis ,neural regeneration ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.
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- 2017
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5. Premature Myocardial Infarction: Genetic Variations in SIRT1 Affect Disease Susceptibility
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Aylin Hatice Yamac, Omer Uysal, Ziya Ismailoglu, Mehmet Ertürk, Mert Celikten, Ahmet Bacaksiz, and Ulkan Kilic
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Objectives. Premature myocardial infarction (PMI) is an uncommon disease, and its incidence varies between 2% and 10%, rising, depending on genetic susceptibility under the influence of lifestyle. The purpose of this study was to investigate the association between SIRT1 single nucleotide polymorphisms (SNPs), SIRT1, and eNOS (endothelial nitric oxide synthase) protein expressions, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in young patients with premature ST-elevation myocardial infarction (STEMI). Methods. Genotyping of the three single-nucleotide polymorphisms (rs7895833 A > G in the promoter region, rs7069102 C > G in intron 4, and rs2273773 C > T in exon 5) in SIRT1 gene was performed in 108 consecutive patients (87.0% were men with a mean age of 40.74 ± 3.82 years) suffering from ST-elevation myocardial infarction at the age of ≤45 and 91 control subjects. Results. The risk for myocardial infarction was increased by 2.31 times in carriers of CC or CG genotypes. SIRT1 protein levels were enhanced and endothelial nitric oxide synthase levels were diminished in ST-elevation myocardial infarction patients regardless of the underlying gene variant. There was no correlation between SIRT1 expression and the amount of endothelial nitric oxide synthase, total antioxidant status, total oxidant status, and oxidative stress index levels in patients and in the control group either. Conclusions. SIRT1 single-nucleotide polymorphisms were associated with premature myocardial infarction, which affected the SIRT1 and endothelial nitric oxide synthase protein expression, irrespective of the underlying SIRT1 genotype.
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- 2019
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6. High Levels of SIRT1 Expression as a Protective Mechanism Against Disease-Related Conditions
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Birsen Elibol and Ulkan Kilic
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SIRT1 expression ,oxidative stress ,metabolic diseases ,cardiovascular diseases ,neurodegenerative diseases ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
SIRT1 protein, a member of Silent Information Regulator 2 (Sir2) protein family, have gained considerable attention as epigenetic regulators for a great area in the human physiology. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, cardiovascular diseases, cancer and neurodegeneration. Here, we provide an overview of the association of the increasing level of SIRT1 protein for regulating some disease related conditions such as obesity, cardiovascular diseases and neurodegeneration. This review also provides a detailed molecular understanding of the interaction of the some basic molecules with increasing SIRT1 levels rather than reduction of the SIRT1 expression. In this context, the current approaches to enhancing the expression of SIRT1 points the importance of epigenetics in several age-related diseases to provide a healthy aging by developing novel therapies which can prevent or damp the progression of some diseases.
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- 2018
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7. Statin and MTHFR C677T Polymorphism in Patients with Cardiovascular Diseases
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Muzeyyen IZMIRLI, Ahmet BACAKSIZ, Davut ALPTEKIN, Omer UYSAL, and Ulkan KILIC
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MTHFR ,cardiovascular disease ,statin ,pharmacogenetics ,Medicine (General) ,R5-920 - Abstract
Objective:Cardiovascular disease (CVD) is the leading cause of death worldwide. The methylenetetrahydrofolate reductase (MTHFR) gene, located on the short (p) arm of chromosome 1 at position 36.3 (1p36.3), might be a possible risk factor for the pharmacogenetics in CVD. A common polymorphism in MTHFR (C677T, Ala→Val) decreases this enzyme activity and increases the homocysteine concentrations, predisposing one to heart disease. Alternatively, statins, cholesterol-reducing agents, are also used to reduce the homocysteine blood concentrations; the aim of the present study was to evaluate how the genotype frequencies of the MTHFR C677T polymorphism, namely rs1801133, change in the cardiovascular system in patients treated with statin.Methods:In this study, the genotype distribution of the MTHFR C677T polymorphism in CVD patients treated with statin (hydrophilic and lipophilic) (n=290) and healthy controls (n=151) was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Results:In this study, a statistically significant difference in genotype frequencies for the MTHFR C677T polymorphism was found between CVD patients treated with statin and controls (p=0.037).Conclusion:For the first time, we demonstrate a relation between a MTHFR gene polymorphism and CVD in patients treated with statins in the Turkish population.
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- 2014
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8. TLR-4 deficiency protects against focal cerebral ischemia and axotomy-induced neurodegeneration
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Ulkan Kilic, Ertugrul Kilic, Christian M. Matter, Claudio L. Bassetti, and Dirk M. Hermann
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Innate immune system ,Danger signaling ,Ischemic stroke ,Neurodegeneration ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The pattern recognition receptor toll-like receptor (TLR)-4 mediates innate danger signaling in the brain, being activated in response to lipopolysaccharide. Until now, its role in the degenerating brain remained unknown. We here examined effects of a loss-of-function mutation of TLR-4 in mice submitted to transient focal cerebral ischemia and retinal ganglion cell (RGC) axotomy, which are highly reproducible and clinically relevant in vivo models of acute and subacute neuronal degeneration. We show that TLR-4 deficiency protects mice against ischemia and axotomy-induced RGC degeneration. Decreased phosphorylation levels of the mitogen-activated kinases ERK-1/-2, JNK-1/-2 and p38 together with reduced inducible NO synthase levels in injured neurons of TLR-4 mutant mice suggests that TLR-4 deficiency downscales parenchymal stress responses, thereby enhancing neuronal survival. At the same time, densities of MPO+ neutrophils and Iba1+ microglial cells were increased in the brains of TLR-4 mutant animals, pointing towards a futile inflammatory response aiming to compensate lost functions. Our data indicate that innate immunity may represent an attractive target for neuroprotective treatments in stroke and neurodegeneration.
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- 2008
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9. A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.
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Ulkan Kilic, Ozlem Gok, Ufuk Erenberk, Mehmet Rusen Dundaroz, Emel Torun, Yasar Kucukardali, Birsen Elibol-Can, Omer Uysal, and Tolga Dundar
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Medicine ,Science - Abstract
Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene.
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- 2015
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10. SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases.
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Ulkan Kilic, Ozlem Gok, Ahmet Bacaksiz, Muzeyyen Izmirli, Birsen Elibol-Can, and Omer Uysal
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Medicine ,Science - Abstract
Cardiovascular disease (CVD), the leading cause of death worldwide, is related to gene-environment interactions due to epigenetic factors. SIRT1 protein and its downstream pathways are critical for both normal homeostasis and protection from CVD-induced defects. The aim of this study was to investigate the association between SIRT1 single nucleotide polymorphisms (SNPs) (rs7895833 A>G in the promoter region, rs7069102 C>G in intron 4 and rs2273773 C>T in exon 5 silent mutation) and SIRT1 and eNOS (endothelial nitric oxide synthase) protein expression as well as total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in CVD patients as compared to controls. The frequencies of mutant genotypes and alleles for rs7069102 and rs2273773 were significantly higher in patients with CVD compared to control group. The risk for CVD was increased by 2.4 times for rs7069102 and 1.9 times for rs2273773 in carriers of mutant allele compared with carriers of wild-type allele pointing the protective role of C allele for both SNPs against CVD. For rs7895833, there was no significant difference in genotype and allele distributions between groups. SIRT1 protein, TAS, TOS and OSI levels significantly increased in patients as compared to control group. In contrast, level of eNOS protein was considerably low in the CVD patients. An increase in the SIRT1 expression in the CVD patients carrying mutant genotype for rs7069102 and heterozygote genotype for all three SNPs was observed. This is the first study reporting an association between SIRT1 gene polymorphisms and the levels of SIRT1 and eNOS expressions as well as TAS, TOS and OSI.
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- 2014
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11. Uncovering the antidiabetic potential of heart-friendly and diuretic bioactive compounds through computer-based drug design.
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Nilufer Ercin, Nail Besli, and Ulkan Kilic
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- 2024
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12. Hyperthermia alters neurobehavior by affecting cell proliferation and neuronal survival in young male rats
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Fatih Mete, Signem Eyuboglu, Ayca Vitrinel, Ulkan Kilic, Cihan Suleyman Erdogan, Ertugrul Kilic, and Bayram Yilmaz
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Developmental Neuroscience ,Developmental Biology - Published
- 2023
13. Determination of Rh type and gender using circulating cell-free fetal DNA in early pregnancy of Rh negative women in Turkey
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Tugba Elgun, Yasemin Musteri Oltulu, Asiye Gok Yurttas, Umut Agyuz, Fulya Ozkal Molla, Ulkan Kilic, and Tıp Fakültesi
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Non-Invasive Prenatal Diagnosis ,RHD Type ,Biochemistry (medical) ,Clinical Biochemistry ,cff-DNA ,Hematology ,Real-Time PCR - Abstract
Introduction: Choosing the right clinical approach for early and reliable diagnosis/screening is becoming more important day by day. The aim of the study was to determine the early RhD type with cff-DNA obtained from maternal plasma, especially in the light of recent developments. In this way, it is aimed to apply Rh Ig only to mothers who are determined to have RhD (+) fetuses and to prevent unnecessary further tests that may possess a risk for RhD (-) fetuses. Methods: Prediction of fetal gender and RH genotype was performed by using RT-qPCR method. With simultaneous amplification of sequences of SRY, DYS14 and RH genes (exon 7 and exon 10). Fetal gender and RhD were determined in 30 RHD (-) pregnant women with cfDNA. Results: As a result of genotyping, the gender of 67% (20/30) fetuses was determined as male; the gender of 33% (10/30) fetuses was determined as female in a sample group of 30 pregnancies. It was determined that the DYS14 100% (20/20) gene was more sensitive than the SRY 97% (18/20) gene in gender determination after examining prenatal and postnatal results. As a result of the analysis, the presence of 17% (5/30) RhD (-) fetuses and 83% (25/30) RhD (+) fetuses were determined which is 100% compatible with postnatal results. Discussion: Detecting fetal RhD gene in maternal plasma made an important contribution to its use in non-invasive prenatal screening. This study shows that unnecessary intervention and cost can be avoided with successful genotyping analysis performed with RT-qPCR.
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- 2023
14. Exosomal circRNA-miRNA Expression profile from plasma in Alzheimer’s Disease Patients by Bioinformatics and Integrative Analysis
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Nail Besli, Bahar Sarikamis, Rabia Kalkan Cakmak, and Ulkan Kilic
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Background Alzheimer's disease (AD) is an age-dependent neurodegenerative ailment globally. Compelling evidence suggests the function of exosomal non-coding RNAs has been associated with the progression of AD but whose exosomal-linked non-coding RNAs mediated regulatory mechanisms are broadly unlit. This study, therefore, set out with the aim of exploring the exosomal circRNA-miRNA networks in the plasma of AD patients. Methods and Results Data of 3 samples from each group (healthy, mild cognitive impairment (MCI), and AD) were fetched from ArrayExpress. The MCI and AD groups were compared with the healthy group by screening for differentially expressed miRNAs (DEmiRs) and circRNAs (DEcircRs) in plasma exosomes. Subsequently, common DEmiRs and DEcircRs for both MCI and AD groups were evaluated to identify gene ontologies, pathways, and networks. Lastly, the analysis of the PPI (protein–protein interaction) network and hub genes selection were performed. A total of common 19 (7 upregulated and 12 downregulated) DEmiRs and 24 DEcircRs were identified. It was predicted 4559 target genes for upregulated DemiRs, while 6504 target genes for downregulated DEmiRs and most of the target genes were associated with the PI3K-Akt pathway and that they were mostly regulated by hsa-mir-615-3p, hsa-mir-196a-5p, hsa-let-7c-5p, hsa-let-205-5p, hsa-mir-185-3p, hsa-mir-185-5p, hsa-mir-374a-5p, hsa-mir-374a-3p. Also, 9 hub genes (CCNE2, CCND1, CDK6, ACTB, MAPK1, AKT1, GSK3B, IGF1R, HSP90AA) were uncovered as the genes most associated with AD by a PPI network using Cytoscape plug-in cytohubba. Conclusions Our outcomes exhibit a new outlook on a possible exosomal-linked miRNA-circRNA network in the pathogenesis of AD.
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- 2022
15. Umbilical cord levels of macrophage migration inhibitory factor in neonatal respiratory distress syndrome
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Süleyman Bayraktar, Bilge Tanyeri Bayraktar, Ulkan Kilic, and BAYRAKTAR, Bilge
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Male ,medicine.medical_specialty ,Neonatal respiratory distress syndrome ,lung maturation ,Gestational Age ,Antenatal steroid ,Gastroenterology ,Umbilical cord ,Article ,Umbilical Cord ,Pregnancy ,Internal medicine ,Birth Weight ,Humans ,Medicine ,Macrophage Migration-Inhibitory Factors ,Macrophage migration inhibitory factor ,Respiratory Distress Syndrome, Newborn ,Respiratory distress ,business.industry ,Infant, Newborn ,Gestational age ,General Medicine ,respiratory system ,Fetal Blood ,Delivery mode ,medicine.disease ,respiratory distress syndrome ,medicine.anatomical_structure ,Cord blood ,Female ,Steroids ,neonate ,business ,Infant, Premature - Abstract
Background/aim: We aimed to evaluate the association of the umbilical cord macrophage migration inhibitory factor (MIF) with the respiratory distress syndrome (RDS) in preterm infants. Materials and methods: A total of eighty six preterm infants (38 with RDS and 48 without RDS) were involved in the study. ELISA is the technique assaying MIF values. Results: The mean of the infants’ gestational ages and birth weights were significantly different (P = 0.0001). There were no significant differences in sex, delivery mode or exposure to antenatal steroid among the groups (P > 0.05). Umbilical cord MIF levels of the infants were not correlated with gestational age and birth weight (Spearman’s rho = –0.22 and 0.28 respectively, P > 0.05). There was no statistically significant difference in umbilical cord MIF levels of infants whether or not they were administered antenatal steroid (median:17.88 vs. median:17.60, Mann–Whitney U test, P = 0.42). Cord serum MIF levels were higher (mean, 17.09 ± 5.86 ng/mL) in the RDS group than in the non-RDS group (mean, 14.72 ± 4.18 ng/mL) (P = 0.005). Conclusion: This study shows that, MIF level is higher in the cord blood of the infants with RDS than of the infants without RDS. This supports that MIF expression begins in prior to the birth of the preterm infants and MIF has enhancing impact on the lung development of premature babies. With future studies, the assessment of the cord MIF levels at the bedside may be beneficial for the diagnosis and treatment of RDS, and taking actions to prevent long-term consequences. Bezmiâlem Vakıf Üniversitesi
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- 2021
16. Dual action of exosomes derived from in vitro Aβ toxicity model: The role of age for pathological response
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Merve Beker, Necmeddin Gunay, Bahar Sarikamis, Rabia Kalkan Cakmak, Nilufer Ercin, Mehmet Ozgen Altintas, Serdar Altunay, Mustafa Caglar Beker, Duygu Sari Ak, and Ulkan Kilic
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Exosome ,Aging ,Health (social science) ,Survival ,Neurogenesis ,Amyloid β ,Geriatrics and Gerontology ,Hippocampus ,Gerontology - Abstract
Exosomes released from different cell types of the central nervous system play an essential role in the patho-genesis of Alzheimer's disease (AD). In this study, we aimed to create an animal model by injecting exosomes that carry AD markers into the brain to shed light on the mechanism behind Alzheimer's pathology. Exosomes obtained from mouse Neuro2A, to which A beta toxicity model applied, were used as a mediator to build an AD phenotype. For this purpose, exosomes were administered into hippocampal CA3 region of mice with different ages. Firstly, the possible role of exosomes on brain volume was analyzed. Then, neurons and astrocytes were evaluated for survival. In addition, the progenitor cells' differentiation capacity was investigated via BrdU staining. AKT signaling pathway components were examined to detect the molecular mechanisms behind the exosomal function. We found different responses in different age groups. Expression of APP upregulated only in young animals upon delivery of A beta-exosomes. Interestingly, young animals represented increased numbers of neurons in the hippocampus, and neurogenesis was found to be restricted after A beta-Ex injections. However, in relation to exosome administration, the glial intensity increased in aged animals. Lastly, phosphorylation of survival kinase AKT was downregulated due to the presence of A beta in both young and old animals. The findings reveal that the exosomes from an in vitro A beta toxicity model may induce different responses in an age-dependent manner. This study is the first to report the relationship between exosomal function and aging by evaluating the key molecules.
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- 2023
17. Melatonin affects the release of exosomes and tau-content in in vitro amyloid-beta toxicity model
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Ulkan Kilic, Burak Yulug, Seyda Cankaya, Ertugrul Kilic, Muzaffer Beyza Ozansoy, Sule Goktekin, Mehmet Ozansoy, ALKÜ, and 0-belirlenecek
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SH-SY5Y ,Amyloid beta ,tau Proteins ,Alzheimer's Disease ,Exosomes ,Exosome ,Melatonin ,03 medical and health sciences ,Pineal gland ,0302 clinical medicine ,Cell Line, Tumor ,Physiology (medical) ,Humans ,Medicine ,Viability assay ,Neurons ,Amyloid beta-Peptides ,biology ,business.industry ,Cell growth ,Amyloid-Beta ,General Medicine ,Alzheimer's disease ,Microvesicles ,Cell biology ,medicine.anatomical_structure ,Neurology ,030220 oncology & carcinogenesis ,biology.protein ,Surgery ,Neurology (clinical) ,Amyloid-beta ,Tau ,business ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,medicine.drug - Abstract
PubMed: 32061493 Background: Recent studies have been revealed that oxidative damage is the main cause of aging and age-related neurodegenerative diseases like Alzheimer's disease (AD). Melatonin is secreted from the pineal gland and its secretion has been found to be altered in AD. In the last decade the role of exosomes in spreading toxic proteins and inducing the propagation of diseases like AD has been discussed. However, it is not known how melatonin affects the amount of exosomes released from the cells and the content of the exosomes. Objective: Herein, we investigated the possible role of melatonin treatment in the releasing of exosomes and exosomal tau content in an in vitro A? toxicity model. Method: SH-SY5Y cell line was used. The optimum concentration of A? was determined by cell viability and cell proliferation tests. Melatonin (100 µM) was applied before and after A? application. Total exosomes isolated from cell culture media were immunoprecipitated. The amount of released exosomes and their tau content were analyzed by Western blots. Results: Our data demonstrated for the first time that melatonin treatment clearly affected the amount of released exosomes. It would decrease the amyloid beta load and toxicity by inhibiting exosome release. We also demonstated that melatonin also affected the level of tau carried by exosomes depending on whether melatonin was applied before or after A? application. Conclusion: It is considered that the effect of melatonin in the release of exosomes and exosomal tau content would contribute the development of therapeutic strategies in AD and related disorders. © 2019 Elsevier Ltd
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- 2020
18. Interaction of melatonin and Bmal1 in the regulation of PI3K/AKT pathway components and cellular survival
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Berrak Caglayan, Ertugrul Kilic, Ahmet Tarik Baykal, Aysun Çağlayan, Mustafa Çağlar Beker, Esra Yalcin, Ahmet Burak Çağlayan, Ulkan Kilic, Russel J. Reiter, Taha Kelestemur, and Acibadem University Dspace
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Male ,Cell signaling ,Focal Cerebral-Ischemia ,endocrine system ,Cell Survival ,lcsh:Medicine ,Clock Gene-Expression ,Circadian mechanisms ,Circadian-Rhythm ,Hippocampus ,Article ,Brain Ischemia ,Cell Line ,Melatonin ,Brain-Injury ,Phosphatidylinositol 3-Kinases ,Receptors ,medicine ,Mechanisms ,Animals ,Phosphorylation ,lcsh:Science ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Neurons ,Multidisciplinary ,Suprachiasmatic nucleus ,Chemistry ,Akt/PKB signaling pathway ,Kinase ,TOR Serine-Threonine Kinases ,lcsh:R ,ARNTL Transcription Factors ,Cellular neuroscience ,Cell biology ,Mice, Inbred C57BL ,Oxygen ,Stroke ,Glucose ,Disruption ,lcsh:Q ,Sleep ,Proto-Oncogene Proteins c-akt ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Signal Transduction - Abstract
The circadian rhythm is driven by a master clock within the suprachiasmatic nucleus which regulates the rhythmic secretion of melatonin. Bmal1 coordinates the rhythmic expression of transcriptome and regulates biological activities, involved in cell metabolism and aging. However, the role of Bmal1 in cellular- survival, signaling, its interaction with intracellular proteins, and how melatonin regulates its expression is largely unclear. Here we observed that melatonin increases the expression of Bmal1 and both melatonin and Bmal1 increase cellular survival after oxygen glucose deprivation (OGD) while the inhibition of Bmal1 resulted in the decreased cellular survival without affecting neuroprotective effects of melatonin. By using a planar surface immunoassay for PI3K/AKT signaling pathway components, we revealed that both melatonin and Bmal1 increased phosphorylation of AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3αβ, and p70S6K. In contrast, inhibition of Bmal1 resulted in decreased phosphorylation of these proteins, which the effect of melatonin on these signaling molecules was not affected by the absence of Bmal1. Besides, the inhibition of PI3K/AKT decreased Bmal1 expression and the effect of melatonin on Bmal1 after both OGD in vitro and focal cerebral ischemia in vivo. Our data demonstrate that melatonin controls the expression of Bmal1 via PI3K/AKT signaling, and Bmal1 plays critical roles in cellular survival via activation of survival kinases.
- Published
- 2019
19. Striatal dopaminergic neurons as a potential target for GDNF based ischemic stroke therapy
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Merve Beker, Ulkan Kilic, Mustafa Çağlar Beker, Ahmet Burak Çağlayan, Ertugrul Kilic, Gamze Torun Kose, and Busenur Bolat
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Male ,medicine.medical_specialty ,Tyrosine 3-Monooxygenase ,Dopamine ,Population ,Striatum ,Neuroprotection ,Mice ,Neurotrophic factors ,Ischemia ,Internal medicine ,medicine ,Glial cell line-derived neurotrophic factor ,Animals ,Glial Cell Line-Derived Neurotrophic Factor ,education ,Ischemic Stroke ,education.field_of_study ,Tyrosine hydroxylase ,biology ,urogenital system ,business.industry ,Dopaminergic Neurons ,Lentivirus ,Dopaminergic ,Gene Therapy ,General Medicine ,GDNF ,Mice, Inbred C57BL ,Endocrinology ,nervous system ,biology.protein ,business ,medicine.drug ,Transcription Factors - Abstract
Background/aim Glial cell-line derived neurotrophic factor (GDNF) is a well-known regulatory neurotrophic factor on dopaminergic neurons. Several pathologies have been documented so far in case of any impairment in the dopaminergic system. This study aimed to investigate the potential protective role of lentiviral GNDF delivery on the small population of tyrosine hydroxylase (TH) positive dopamine producing striatal neurons after ischemic stroke. Materials and methods Fourteen C57BL/6J male mice (8-10 weeks) were intracerebrally treated with lentiviral GDNF (Lv-GDNF) or vehicle. Ten days after injections, cerebral ischemia was induced by blockage of the middle cerebral artery. Animals were terminated 72 hours after ischemia, and their brains were taken for histological and molecular investigations. Following confirmation of GDNF overexpression, TH immunostaining and immunoblotting were used to evaluate the role of GDNF on dopaminergic neurons. Next, Fluro Jade C staining was implemented to examine the degree of neuronal degeneration at the damaged parenchyma. Results Neither the amount of TH positive dopaminergic neurons nor the expression of TH changed in the Lv-GDNF treated animals comparing to the vehicle group. On the other hand, GDNF exposure caused a significant increase in the expression of Nurr1, an essential transcription factor for dopaminergic neurons and Gap43, growth and plasticity promoting protein, in the ischemic striatum. Treatment with Lv-GDNF gave rise to a significant reduction in the number of degenerated neurons. Finally, enhanced GDNF expression also induced expression of an important stress related transcription factor NF-?B as well as the nitric oxide synthase enzymes iNOS and nNOS in the contralesional hemisphere. Conclusion Considering these results together, GDNF?s impact on the survival of striatal dopaminergic neurons is not outstanding for its neuroprotective role. However, it seems that GDNF conducts several signaling pathways by acting on key transcription factors and shows its protective feature by fine tuning the degeneration related processes.
- Published
- 2021
20. Integrin alpha 5 beta 1 mediated cellular reorganization in human mesenchymal stem cells during neuronal differentiation
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Nihal Karakaş and Ulkan Kilic
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Nervous system ,Cancer Research ,Cell ,Integrin ,General Biochemistry, Genetics and Molecular Biology ,Downregulation and upregulation ,medicine ,Cell Adhesion ,Humans ,Receptor ,Pharmacology ,biology ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell biology ,Extracellular Matrix ,Fibronectin ,Cytosol ,medicine.anatomical_structure ,nervous system ,biology.protein ,Integrin α5β1 ,Neuronal Differentiation ,Research Article ,Integrin alpha5beta1 - Abstract
Background/Aim: Mesenchymal stem cells (MSCs) have been widely used for yielding neurons in culture to study nervous system pathologies and develop regenerative approaches. In this study, cellular rearrangements of human MSCs related to the expression of the fibronectin common receptor integrin alpha 5 beta 1 and its cell surface localization during neuronal differentiation, were examined. Materials and Methods: Proliferation kinetics of neuronal induced hMSCs (hMd-Neurons) were quantified by BrdU assay, and hMd-Neurons were immunostained for neuronal marker expression. Additionally, cDNA and protein samples were collected at different time points for integrin alpha 5 beta 1 expression analysis. Results: Endogenous integrin alpha 5 beta 1 expression was significantly upregulated by day 6 and maintained until day 12. Cell surface localization of alpha 5 beta 1 integrin was increased by day 6; the integrin was internalized into the cytosol by day 12. Conclusion: Integrin dynamics around day 6 of differentiation might be involved in neuronal differentiation and maturation or specification of hMd-Neurons. Istanbul Medipol University, Scientific Research Projects Committee (BAP)
- Published
- 2021
21. Delayed Therapeutic Administration of Melatonin Enhances Neuronal Survival Through AKT and MAPK Signaling Pathways Following Focal Brain Ischemia in Mice
- Author
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Ulkan Kilic, Birsen Elibol, Ahmet Burak Caglayan, Mustafa Caglar Beker, Merve Beker, Burcugul Altug-Tasa, Omer Uysal, Bayram Yilmaz, Ertugrul Kilic, and ELİBOL, BİRSEN
- Subjects
Cell Survival ,Kilic U., ELİBOL B., ÇAĞLAYAN A. B. , Beker M. C. , Beker M., Altug-Tasa B., UYSAL Ö., YILMAZ B., KILIÇ E., -Delayed Therapeutic Administration of Melatonin Enhances Neuronal Survival Through AKT and MAPK Signaling Pathways Following Focal Brain Ischemia in Mice-, JOURNAL OF MOLECULAR NEUROSCIENCE, 2022 ,Apoptosis ,General Medicine ,Ischemic Brain ,Brain Ischemia ,Stroke ,Cellular and Molecular Neuroscience ,Mice ,Brain Plasticity ,Animals ,Proto-Oncogene Proteins c-akt ,Melatonin ,Signal Transduction - Abstract
Melatonin has a role in the cell survival signaling pathways as a candidate for secondary stroke prevention. Therefore, in the present study, the coordination of ipsilateral and contralateral hemispheres to evaluate delayed post-acute effect of melatonin was examined on recovery of the cell survival and apoptosis after stroke. Melatonin was administered (4 mg/kg/day) intraperitoneally for 45 days, starting 3 days after 30 min of middle cerebral artery occlusion. The genes and proteins related to the cell survival and apoptosis were investigated by immunofluorescence, western blotting, and RT-PCR techniques after behavioral experiments. Melatonin produced delayed neurological recovery by improving motor coordination on grip strength and rotarod tests. This neurological recovery was also reflected by high level of NeuN positive cells and low level of TUNEL-positive cells suggesting enhanced neuronal survival and reduced apoptosis at the fifty-fifth day of stroke. The increase of NGF, Nrp1, c-jun; activation of AKT; and dephosphorylation of ERK and INK at the fifty-fifth day showed that cell survival and apoptosis signaling molecules compete to contribute to the remodeling of brain. Furthermore, an increase in the CREB and Atf-1 expressions suggested the melatonin-s strong reformative effect on neuronal regeneration. The contralateral hemisphere was more active at the latter stages of the molecular and functional regeneration which provides a further proof of principle about melatonin-s action on the promotion of brain plasticity and recovery after stroke.
- Published
- 2021
22. Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders
- Author
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Giovanni Coppola, Suzee E. Lee, Dimitra Sali, Gülsen Babacan-Yıldız, Carl W. Cotman, Helena C. Chui, Jennifer S. Yokoyama, Federica Agosta, Dimitrios Agiomyrgiannakis, Adam L. Boxer, Massimo Filippi, Chris Zarow, Ulkan Kilic, Jorge L. Juncos, Anna Karydas, Marla Gearing, John Papatriantafyllou, Gary W. Small, Ariane H. Ayer, Jason A. Chen, John M. Ringman, Joel H. Kramer, Charles DeCarli, Karen H. Gylys, Allan I. Levey, Kevin Wojta, Niki Tsinia, David A. Bennett, Eliana Marisa Ramos, Bruce L. Miller, Deepika Dokuru, Mario F. Mendez, Vasiliki Kamtsadeli, Ayer, Ariane H, Wojta, Kevin, Ramos, Eliana Marisa, Dokuru, Deepika, Chen, Jason A, Karydas, Anna M, Papatriantafyllou, John D, Agiomyrgiannakis, Dimitrio, Kamtsadeli, Vasiliki, Tsinia, Niki, Sali, Dimitra, Gylys, Karen H, Agosta, Federica, Filippi, Massimo, Small, Gary W, Bennett, David A, Gearing, Marla, Juncos, Jorge L, Kramer, Joel, Lee, Suzee E, Yokoyama, Jennifer S, Mendez, Mario F, Chui, Helena, Zarow, Chri, Ringman, John M, Kilic, Ulkan, Babacan-Yildiz, Gülsen, Levey, Allan, Decarli, Charles S, Cotman, Carl W, Boxer, Adam L, Miller, Bruce L, Coppola, Giovanni, and BABACAN YILDIZ, GÜLSEN
- Subjects
Male ,Oncology ,Aging ,amyotrophic lateral sclerosis ,Internationality ,Disease ,Neurodegenerative ,Alzheimer's Disease ,frontotemporal dementia ,Cohort Studies ,0302 clinical medicine ,Immunologic ,Receptors ,TREM2 ,2.1 Biological and endogenous factors ,genetics ,030212 general & internal medicine ,Receptors, Immunologic ,Ayer A., Wojta K., Ramos E., Dokuru D., Chen J., Karydas A., Papatriantafyllou J., Agiomyrgiannakis D., Kamtsadeli V., Tsinia N., et al., -Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders.-, Alzheimer disease and associated disorders, cilt.33, ss.327-330, 2019 ,Aetiology ,Amyotrophic lateral sclerosis ,Membrane Glycoproteins ,Neurodegenerative Diseases ,Psychiatry and Mental health ,Clinical Psychology ,Frontotemporal Dementia ,Neurological ,Cohort ,Female ,Cognitive Sciences ,Alzheimer's disease ,Frontotemporal dementia ,Cohort study ,medicine.medical_specialty ,Genotype ,Clinical Sciences ,association study ,Article ,Progressive supranuclear palsy ,03 medical and health sciences ,Rare Diseases ,mild cognitive impairment ,Alzheimer Disease ,Clinical Research ,Internal medicine ,Acquired Cognitive Impairment ,medicine ,Humans ,Genetic Predisposition to Disease ,Cognitive Dysfunction ,Aged ,business.industry ,Amyotrophic Lateral Sclerosis ,Neurosciences ,Genetic Variation ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,progressive supranuclear palsy ,corticobasal syndrome ,medicine.disease ,Brain Disorders ,Geriatrics ,Dementia ,Geriatrics and Gerontology ,business ,Gerontology ,030217 neurology & neurosurgery - Abstract
OBJECTIVE: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer’s disease, while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3,058 patients clinically diagnosed with Alzheimer’s disease, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5,089 control subjects. RESULTS: We observed a significant association between the R47H variant and Alzheimer’s disease, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with Alzheimer’s disease. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.
- Published
- 2019
23. Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice
- Author
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Mehmet Ozansoy, Rumeyza Kazancioglu, Ulkan Kilic, Arzu Şakul, Yasemin Yozgat, Şule Ayla, Kazim Sahin, Birsen Elibol, Mehmet Yalçın Günal, Huveyda Basaga, ALKÜ, 0-belirlenecek, ELİBOL, BİRSEN, Sakul, Arzu Istanbul Medipol Univ, Sch Med, Dept Med Pharmacol, Istanbul, Turkey, Ozansoy, Mehmet Istanbul Medipol Univ, Sch Med, Dept Physiol, Istanbul, Turkey, Elibol, Birsen Bezmialem Vakif Univ, Fac Med, Dept Med Biol, Istanbul, Turkey, Ayla, Sule Istanbul Medipol Univ, Sch Med, Dept Histol & Embryol, Istanbul, Turkey, Gunal, Mehmet Yalcin Alanya Alaaddin Keykubat Univ, Dept Physiol, Sch Med, Antalya, Turkey, Yozgat, Yasemin Istanbul Medipol Univ, Regenerat & Restorat Med Res Ctr REMER, Istanbul, Turkey, Basaga, Huveyda Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, Istanbul, Turkey, Sahin, Kazim Firat Univ, Fac Vet Med, Dept Anim Nutr, Elazig, Turkey, Kazancioglu, Rumeyza Bezmialem Vakif Univ, Fac Med, Dept Nephrol, Istanbul, Turkey, Kilic, Ulkan Univ Hlth Sci, Fac Med, Dept Med Biol, Istanbul, Turkey, gunal, mehmet yalcin -- 0000-0001-7702-2441, and Sahin, Kazim -- 0000-0001-9542-5244
- Subjects
cisplatin-induced nephrotoxicity ,mice ,Physiology ,0206 medical engineering ,02 engineering and technology ,Biology ,Pharmacology ,squalene ,medicine.disease_cause ,Microbiology ,Article ,Nephrotoxicity ,Proinflammatory cytokine ,03 medical and health sciences ,Squalene ,chemistry.chemical_compound ,0302 clinical medicine ,Genetics ,medicine ,oxidative-stress ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cisplatin ,Kidney ,AKT ,Cell Biology ,Sakul A., Ozansoy M., ELİBOL B., Ayla S., Gunal M. Y. , Yozgat Y., Basaga H., Sahin K., KAZANCIOĞLU R., Kilic U., -Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice-, TURKISH JOURNAL OF BIOLOGY, cilt.43, ss.179-188, 2019 ,020601 biomedical engineering ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,mTOR ,General Agricultural and Biological Sciences ,Oxidative stress ,Biyoloji ,medicine.drug - Abstract
WOS: 000471268100003 The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-gamma) decreased in the cisplatin and squalene cotreated mice compared to cisplatin-treated mice. Squalene treatment also increased the activation of protein kinase B (AKT). Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin (mTOR) and histopathological damages were reversed by squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidney through activation of AKT/mTOR signaling pathway by regulating the balance of the redox system due to its antioxidative effect.
- Published
- 2019
24. The therapeutic role of minocycline in Parkinson’s disease
- Author
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Ulkan Kilic, Baris Cankaya, Seyda Cankaya, Ertugrul Kilic, and Burak Yulug
- Subjects
0301 basic medicine ,Parkinson's disease ,Traumatic brain injury ,Ischemia ,Review ,Pharmacology ,Neuroprotection ,03 medical and health sciences ,minocycline ,0302 clinical medicine ,medicine ,Amyotrophic lateral sclerosis ,business.industry ,Multiple sclerosis ,lcsh:RM1-950 ,Neurodegeneration ,neurodegeneration ,General Medicine ,Minocycline ,medicine.disease ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Parkinson’s disease ,Molecular Medicine ,neuroprotection ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Minocycline, a semisynthetic tetracycline-derived antibiotic, has been shown to exert anti-apoptotic, anti-inflammatory, and antioxidant effects. Furthermore, there is rapidly growing evidence suggesting that minocycline may have some neuroprotective activity in various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson’s disease (PD), Huntington’s disease, and multiple sclerosis. In this perspective review, we summarize the preclinical and clinical findings suggesting the neuroprotective role of minocycline in PD.
- Published
- 2019
25. Effectiveness of Different Surgical Flap Delay Methods and Their Systemic Toxicities
- Author
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Ulkan Kilic, Ethem Güneren, Halil Ibrahim Canter, Ali Çay, Haci Omer Sagir, Ahmet Kirazoglu, Nebil Yesiloglu, Kemalettin Yildiz, Abdurrahim Kocyigit, Semih Lutfi Mirapoglu, and KOÇYİĞİT, ABDÜRRAHİM
- Subjects
Male ,medicine.medical_specialty ,Surgical Flaps ,Rats, Sprague-Dawley ,03 medical and health sciences ,Necrosis ,0302 clinical medicine ,Male rats ,Medicine ,Flap survival ,Animals ,030223 otorhinolaryngology ,business.industry ,Yildiz K., Mirapoglu S. L. , Kilic U., Guneren E., Kocyigit A., Kirazoglu A., Sagir H. O. , Yesiloglu N., Canter H. I. , Cay A., -Effectiveness of Different Surgical Flap Delay Methods and Their Systemic Toxicities.-, The Journal of craniofacial surgery, 2021 ,Significant difference ,Graft Survival ,Surgical delay ,030206 dentistry ,General Medicine ,Gold standard (test) ,Surgery ,Rats ,Sprague dawley ,Systemic toxicity ,Otorhinolaryngology ,business - Abstract
Objective The surgical flap delaying has been shown to be effective in preventing partial flap loss or in preparing larger flaps. However, there is no gold standard flap delay method in the literature. In this study, the authors aimed to compare 3 types of surgical delay methods to determine which model would increase more flap survival. The authors also investigated the effect of delay methods on circulating mononuclear leukocytes as a parameter of DNA damage. Methods Twenty-four Sprague-Dawley male rats were divided into 4 groups. All subjects had a 10 × 3 cm modified McFarlane flap. Surface area measurements, biopsies, and blood samples were taken on the day of sacrification; 7th day for the control group and 14th day for delay groups. Results Between incisional surgery delay groups, a significant difference was found in necrosis and apoptosis in the bipedicled group, and only necrosis in the tripedicled group compared to the control. In terms of DNA damage, it was found higher in all experimental groups than in the control group. Conclusions Both incisional surgical delay procedures' results were meaningfully effective when only incisions were made without the elevation of flaps. In conclusion, bipedicled incisional surgical delay seems to be the most effective method in McFarlane experimental flap model whereas two-staged surgeries may increase the risk of systemic toxicity.
- Published
- 2021
26. Inflammatory cytokines are in action: Brain plasticity and recovery after brain ischemia due to delayed melatonin administration
- Author
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Burcugul Altug-Tasa, Merve Beker, Mustafa Çağlar Beker, Ertugrul Kilic, Ahmet Burak Çağlayan, Birsen Elibol, Bayram Yilmaz, Ulkan Kilic, and ELİBOL, BİRSEN
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Anti-Inflammatory Agents ,Inflammation ,Proinflammatory cytokine ,Brain Ischemia ,Time-to-Treatment ,Melatonin ,Brain ischemia ,Mice ,Brain Plasticity ,Internal medicine ,Neuroplasticity ,Medicine ,Animals ,Stroke ,Neuronal Plasticity ,biology ,business.industry ,Rehabilitation ,Post-Acute Ischemic Brain ,Pro-Inflammatory Genes ,medicine.disease ,Nitric oxide synthase ,Endocrinology ,biology.protein ,Brain Plasticity and Recovery after Brain Ischemia Due to Delayed Melatonin Administration.-, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, cilt.30, sa.12, ss.106105, 2021 [Kilic U., Elibol B., Beker M., Altug-Tasa B., Caglayan A. B. , Beker M. C. , Yilmaz B., Kilic E., -Inflammatory Cytokines are in Action] ,Cytokines ,Surgery ,Neurology (clinical) ,medicine.symptom ,Nitric Oxide Synthase ,Cardiology and Cardiovascular Medicine ,business ,Stroke recovery ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Objectives Post-ischemic inflammation leads to apoptosis as an indirect cause of functional disabilities after the stroke. Melatonin may be a good candidate for the stroke recovery because of its anti-inflammatory effects. Therefore, we investigated the effect of melatonin on inflammation in the functional recovery of brain by evaluating ipsilesional and contralesional alterations. Materials and Methods Melatonin (4 mg/kg/day) was intraperitoneally administered into the mice from the 3rd to the 55th day of the post-ischemia after 30 min of middle cerebral artery occlusion. Results Melatonin produced a functional recovery by reducing the emigration of the circulatory leukocytes and the local microglial activation within the ischemic brain. Overall, the expression of the inflammation-related genes reduced upon melatonin treatment in the ischemic hemisphere. On the other hand, the expression level of the inflammatory cytokine genes raised in the contralateral hemisphere at the 55th day of the post-ischemia. Furthermore, melatonin triggers an increase in the iNOS expression and a decrease in the nNOS expression in the ipsilateral hemisphere at the earlier times in the post-ischemic recovery. At the 55th day of the post-ischemic recovery, melatonin administration enhanced the eNOS and nNOS protein expressions. Conclusions The present molecular, biological, and histological data have revealed broad anti-inflammatory effects of melatonin in both hemispheres with distinct temporal and spatial patterns at different phases of post-stroke recovery. These outcomes also established that melatonin act recruitment of contralesional rather than of ipsilesional.
- Published
- 2021
27. Corrigendum to: Combined Therapy with Probiotic VSL#3 and Omega-3 Fatty Acids Attenuates Colonic Injury and Inflammation in Chronic DNBS-induced Colitis in Mice
- Author
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Havvanur Yoldas Ilktac, Gul Kiziltan, Asli Devrim Lanpir, Mehmet Ozansoy, Mehmet Y. Gunal, Sine Ozmen Togay, Ilknur Keskin, Ekrem M. Ozdemir, and Ulkan Kilic
- Subjects
General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
We published the abovementioned article about probiotic mixture VSL#3 on October 6, 2021. Since the product was named VSL#3 in our purchasing process in early 2016, it is referred to as VSL#3 in our article. In addition, the product currently known as VSL#3 is not the same as De Simone Formulation. De Simone Formulation is now available as Visbiome® in the United States and Vivomixx® in Europe. The authors would like to apologise for any inconvenience caused
- Published
- 2022
28. Two boron-containing compounds affect the cellular viability of SH-SY5Y cells in an in vitro amyloid-beta toxicity model
- Author
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Ulkan Kilic, Mehmet Özgen Altıntaş, Ertugrul Kilic, Muzaffer Beyza Ozansoy, Necmeddin GÜnay, and Mehmet Ozansoy
- Subjects
inorganic chemicals ,SH-SY5Y ,Physiology ,Amyloid beta ,0206 medical engineering ,chemistry.chemical_element ,02 engineering and technology ,Carbohydrate metabolism ,Biology ,Microbiology ,Article ,Cell wall ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Boron ,GSK-3α/β ,Molecular Biology ,Sirt1 ,neuronal survival ,Boron,neuronal survival,amyloid-beta,Sirt1,GSK-3α/β ,Cell Biology ,020601 biomedical engineering ,In vitro ,amyloid-beta ,GSK-3 Alpha/Beta ,chemistry ,030220 oncology & carcinogenesis ,Toxicity ,Biophysics ,biology.protein ,General Agricultural and Biological Sciences ,Intracellular ,Biyoloji - Abstract
Boron is a naturally occurring trace element found in organic and inorganic complexes. Boron-containing compounds are required for living organisms for diverse metabolic functions, including nitrogen fixation in microorganisms, cell wall stability in plants, and bone and carbohydrate metabolism in animals. The number of studies about the effect of boron in biological model systems is very limited; so far, there has been no study on the correlation between boron and amyloid-beta toxicity. Here, we investigated the possible effects of 2 boron-containing compounds-sodium borate decahydrate and boric acid-against amyloid-beta toxicity. In our in vitro amyloid-beta toxicity model, we showed that these 2 compounds increase the survival of the SH-SY5Y cells. Furthermore, boron in these 2 forms increases the expression of Sirt1, which has protective functions against cellular stress. The compounds also change the expressions of GSK-3 alpha/beta; by doing so, boron may contribute to the stimulation of intracellular prosurvival pathways. This is the first experimental study indicating the prosurvival effect of boron in an amyloid-beta toxicity model.
- Published
- 2020
29. Contralateral hemisphere as a lifeguard which is supported by melatonin for molecular and functional recovery after stroke
- Author
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Burcugul Altug-Tasa, Ahmet Burak Çağlayan, Bayram Yilmaz, Birsen Elibol, Ulkan Kilic, Omer Uysal, Ertugrul Kilic, Mustafa Çağlar Beker, and Merve Beker
- Subjects
Melatonin ,medicine.medical_specialty ,business.industry ,Internal medicine ,Contralateral hemisphere ,medicine ,Cardiology ,medicine.disease ,business ,Functional recovery ,Stroke ,medicine.drug - Abstract
Successful functional recovery from stroke is crucial in the rehabilitation of patients and mainly depends on several ischemia-induced processes, including cell survival and apoptosis. Melatonin is an interesting candidate for secondary stroke prevention due to its effect on signaling pathways. Therefore, we investigated the coordination of ipsilateral and contralateral hemispheres to evaluate delayed post-acute effect of melatonin on recovery of the cell survival and apoptosis after stroke. Melatonin was administered (4 mg/kg/day) intraperitoneally for 45 days, starting 3-day after 30-min of middle cerebral artery occlusion. The genes and proteins related to the cell survival and apoptosis were investigated by immunofluorescence, western blotting and RT-PCR techniques after behavioral experiments. Melatonin produced delayed neurological recovery by improving motor coordination, which was also reflected by enhanced neuronal survival and reduced apoptosis in the post-acute phase of stroke in both contralateral and ipsilateral hemispheres. The increase of NGF, Nrp1, c-jun; activation of AKT; and dephosphorylation of ERK and JNK at the 55th day showed that cell survival and apoptosis signaling molecules compete to contribute to the remodeling of brain. Furthermore, an increase in the CREB and Atf-1 expressions suggested the melatonin's strong reformative effect on neuronal regeneration. The contralateral hemisphere was more active at the latter stages of the molecular and functional regeneration which provides a further proof of principle about melatonin's action on the promotion of brain plasticity and recovery after stroke.
- Published
- 2020
30. Chemopreventive efficacy of stampidine in a murine breast cancer model
- Author
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Ulkan Kilic, Kazim Sahin, Birsen Elibol, Fatih M. Uckun, Taha Koray Sahin, Cemal Orhan, Sanjive Qazi, Mehmet Tuzcu, Ibrahim Hanifi Ozercan, and ELİBOL, BİRSEN
- Subjects
0301 basic medicine ,Time Factors ,Paclitaxel ,9,10-Dimethyl-1,2-benzanthracene ,Clinical Biochemistry ,DMBA ,Breast Neoplasms ,Pharmacology ,medicine.disease_cause ,Article ,Disease-Free Survival ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Breast cancer ,Drug Discovery ,Thymidine Monophosphate ,Medicine ,cancer ,Animals ,Anticarcinogenic Agents ,skin and connective tissue diseases ,stampidine ,Mice, Inbred BALB C ,business.industry ,Stavudine ,Stampidine ,medicine.disease ,Breast Cancer Model ,Survival Rate ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,business ,Carcinogenesis ,medicine.drug ,Dideoxynucleotides - Abstract
BACKGROUND: The purpose of the present study was to examine the chemopreventive effect of Stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine breast cancer model. METHODS: Groups of 20 female mice were challenged with the chemical carcinogen DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine alone, paclitaxel alone, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks. RESULTS: Stampidine treatments resulted in substantially reduced numbers of mammary tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised of BRCA1, p21, Bax, and Bcl-2. CONCLUSION: Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis model of DMBA-induced murine breast cancer.
- Published
- 2020
31. Effects of melatonin and memantine administration on the learning and memory performances of hypoxic juvenile rat pups
- Author
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Burcu Çevreli, Ulkan Kilic, Cigdem Sahbaz, Signem Eyuboglu, Ertugrul Kilic, Birsen Elibol, İstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Siğnem Eyüboğlu / 0000-0002-0253-2217, Eyüboğlu, Siğnem, Siğnem Eyuboğlu / AAW-1273-2020, Siğnem Eyuboğlu / 57210738678, and Tıp Fakültesi
- Subjects
medicine.medical_specialty ,Morris Water Maze ,business.industry ,Memantine ,Morris water navigation task ,General Medicine ,Neonatal hypoxia ,Neonatal Hypoxia ,Melatonin ,Endocrinology ,Learning and Memory ,Internal medicine ,embryonic structures ,Medicine ,business ,medicine.drug ,Juvenile rat - Abstract
Objective: Herein, we aimed to investigate the long-term effects of neonatal hypoxia and the potential protective role of melatonin and memantine on the learning and memory. Methods: Seven-day-old rat underwent right carotid ligation, followed by hypoxia. Rat received Melatonin (MLT) (4 mg/kg), Memantine (MEM) (20 mg/kg), and MLT+MEM combination after hypoxia. We tested these rats for anxiety by elevated O-maze and for spatial learning and memory by Morris water maze (MWM) at postnatal day 45. Results: Hypoxia increased the level of anxiety compared to the control group (p=0.05) while treatment of MLT, MEM, and MLT+MEM ameliorated this effect. In addition, hypoxia produced significant decrease in spatial learning of the rats on the fourth day of training (P=0.05) and the percent time spent in the platform quadrant and the entrance frequencies to the platform quadrant compared to the control group (P=0.049 and P=0.023). Treatment of MLT, MEM, and MLT+MEM after hypoxia improved the performance of the rats at the third (P=0.686, P=0.876, P=0.977, respectively) and fourth day (P=0.738, P=0.553, P=0.789, respectively) of MWM training. The decrease in the percent time spent was ameliorated by the treatment of MLT (P=0.239), MEM (P=0.289), and MLT+MEM (P=0.567) compared to the control group. In addition, MLT treatment significantly increased the entrance frequency to the platform quadrant compared to the hypoxia group (P=0.020). Conclusion: Our data suggested that the MLT was more effective in the release of memory deficits from hypoxia-related damage. MLT might have a therapeutic value in improving hypoxic damage in the developing brain. WOS:000640976900004
- Published
- 2020
32. The association between Hba1c levels, olfactory memory and cognition in normal, pre-diabetic and diabetic persons
- Author
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Ozlem Saatci, Burak Yulug, Lutfu Hanoglu, Seyda Cankaya, Ulkan Kilic, Mehmet Ozansoy, Aysun Isiklar, Ertugrul Kilic, Baris Cankaya, ALKÜ, and 0-belirlenecek
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,Memory Dysfunction ,Olfaction ,Audiology ,Olfactory Memory ,Prediabetic State ,03 medical and health sciences ,Olfaction Disorders ,Olfactory memory ,0302 clinical medicine ,Cognition ,Double-Blind Method ,Memory ,Diabetes mellitus ,medicine ,Diabetes Mellitus ,Immunology and Allergy ,Humans ,Prediabetes ,Prospective Studies ,Prospective cohort study ,education ,Glycated Hemoglobin ,education.field_of_study ,Memory Disorders ,business.industry ,Diabetes ,Middle Aged ,medicine.disease ,Mental Status and Dementia Tests ,Magnetic Resonance Imaging ,Cognitive test ,Smell ,030104 developmental biology ,Female ,business ,030217 neurology & neurosurgery ,Biomarkers ,Memory dysfunction - Abstract
Background and Aim:Recent data have shown that olfactory dysfunction is strongly related to Alzheimer’s Disease (AD) that is often preceded by olfactory deficits suggesting that olfactory dysfunction might represent an early indicator of future cognitive in prediabetes.Methods:We have applied to a group of normal (n=15), prediabetic (n=16) and type 2 diabetic outpatients (n=15) olfactory testing, 1.5-T MRI scanner and detailed cognitive evaluation including the standard Mini-Mental State Examination (MMSE) form, Short Blessed Test (SBT), Letter Fluency Test (LFT) and the category fluency test with animal, Fruit and Vegetable Naming (CFT).Results:We have shown that Odour Threshold (OT), Discrimination (OD), and Identification (OI) scores and most cognitive test results were significantly different in the prediabetes and diabetes group compared to those in the control group. OD and OT were significantly different between the prediabetes and diabetes group, although the cognitive test results were only significantly different in the prediabetes and diabetes group compared to those in the control group. In evaluating the association between OI, OT, OD scores and specific cognitive tests, we have found, that impaired olfactory identification was the only parameter that correlated significantly with the SBT both in the pre-diabetes and diabetes group. Although spot glucose values were only correlated with OT, HbA1c levels were correlated with OT, OD, and OI, as well as results of the letter fluency test suggesting that HbA1c levels rather than the spot glucose values play a critical role in specific cognitive dysfunction.Conclusion:To the best of our knowledge, this is the first prospective study to demonstrate a strong association between olfactory dysfunction and specific memory impairment in a population with prediabetes and diabetes suggesting that impaired olfactory identification might play an important role as a specific predictor of memory decline.
- Published
- 2020
33. Minocycline increases in-vitro cortical neuronal cell survival after laser induced axotomy
- Author
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Ulkan Kilic, Seyda Cankaya, Mehmet Ozansoy, Merve Alokten, Muzaffer Beyza Ozansoy, Ertugrul Kilic, Burak Yulug, Lutfu Hanoglu, ALKÜ, and 0-belirlenecek
- Subjects
Male ,Translational Neuroscience ,Future studies ,Cell Survival ,medicine.medical_treatment ,propidium ,Minocycline ,Pharmacology ,030226 pharmacology & pharmacy ,Neuroprotection ,in-vitro cortical cell culture ,Article ,03 medical and health sciences ,Mice ,Laser-Axotomy ,0302 clinical medicine ,Medicine ,Animals ,Humans ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Cell survival ,Cells, Cultured ,translational neuroscience ,Neurons ,Mice, Inbred BALB C ,Human studies ,Dose-Response Relationship, Drug ,business.industry ,Axotomy ,General Medicine ,Cortical neurons ,In vitro ,Anti-Bacterial Agents ,Neuroprotective Agents ,trauma ,030220 oncology & carcinogenesis ,laser-axotomy ,Laser Therapy ,business ,In-Vitro Cortical Cell Culture ,medicine.drug - Abstract
Background: Antibiotic therapies targeting multiple regenerative mechanisms have the potential for neuroprotective effects, but the diversity of experimental strategies and analyses of non-standardised therapeutic trials are challenging. In this respect, there are no cases of successful clinical application of such candidate molecules when it comes to human patients. Methods: After 24 hours of culturing, three different minocycline (Sigma-Aldrich, M9511, Germany) concentrations (1 μM, 10 μM and 100 μM) were added to the primary cortical neurons 15 minutes before laser axotomy procedure in order to observe protective effect of minocycline in these dosages. Results: Here, we have shown that minocycline exerted a significant neuroprotective effect at 1 and 100μM doses. Beyond confirming the neuroprotective effect of minocycline in a more standardised and advanced in-vitro trauma model, our findings could have important implications for future studies that concentrate on the translational block between animal and human studies. Conclusion: Such sophisticated approaches might also help to conquer the influence of humanmade variabilities in critical experimental injury models. To the best of our knowledge, this is the first study showing that minocycline increases in-vitro neuronal cell survival after laser-axotomy.
- Published
- 2020
34. Specific alterations in the circulating levels of the SIRT1, TLR4, and IL7 proteins in patients with dementia
- Author
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Ertugrul Kilic, Ulkan Kilic, Burak Yulug, Gulsen Babacan Yildiz, Arzu Şakul, Birsen Elibol, Omer Uysal, Kilic, Ulkan Univ Hlth Sci, Fac Med, Dept Med Biol, Tibbiye Cad 38, TR-34668 Istanbul, Turkey, Elibol, Birsen Bezmialem Vakif Univ, Fac Med, Dept Med Biol, Istanbul, Turkey, Uysal, Omer Bezmialem Vakif Univ, Fac Med, Dept Biostat, Istanbul, Turkey, Kilic, Ertugrul Istanbul Medipol Univ, Fac Med, Dept Med Physiol, Istanbul, Turkey, Yulug, Burak Istanbul Medipol Univ, Fac Med, Dept Neurol, Istanbul, Turkey, Sakul, Arzu Sayin Istanbul Medipol Univ, Fac Med, Dept Med Pharmacol, Istanbul, Turkey, Yildiz, Gulsen Babacan Bezmialem Vakif Univ, Fac Med, Dept Neurol, TR-34093 Istanbul, Turkey, Yulug, Burak Alanya Alaaddin Keykubat Univ, Fac Med, Dept Neurol, Alanya, Turkey, Kilic, Ertugrul -- 0000-0001-6494-8923, ALKÜ, 0-belirlenecek, and ELİBOL, BİRSEN
- Subjects
Male ,0301 basic medicine ,Oncology ,Aging ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Inflammation ,Disease ,Logistic regression ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Biochemistry ,Epigenesis, Genetic ,03 medical and health sciences ,Endocrinology ,Sirtuin 1 ,Alzheimer Disease ,Internal medicine ,Genetics ,medicine ,Humans ,Dementia ,TLR4 ,Molecular Biology ,Aged ,Aged, 80 and over ,IL-7 ,kılıç U., Elibol B., Uysal O., Kilic E., Yulug B., Sakul A. S. , Yildiz G. B. , -Specific alterations in the circulating levels of the SIRT1, TLR4, and IL7 proteins in patients with dementia-, EXPERIMENTAL GERONTOLOGY, cilt.111, ss.203-209, 2018 ,business.industry ,Interleukin-7 ,SIRT1 polymorphism ,Neurodegeneration ,Cell Biology ,Middle Aged ,Alzheimer's disease ,medicine.disease ,Toll-Like Receptor 4 ,Logistic Models ,030104 developmental biology ,Oxidative stress ,Case-Control Studies ,Female ,medicine.symptom ,business ,Biomarkers - Abstract
Uysal, Omer/0000-0002-8833-697X; Kilic, Ertugrul/0000-0001-6494-8923; Elibol, Birsen/0000-0002-9462-0862 WOS: 000443177600024 PubMed: 30071285 Sirtuins have gained considerable attention as epigenetic regulators for slowing aging and age-related disorders. The growing association between neurodegeneration and inflammation has led researchers to investigate interactions of sirtuins with inflammatory markers in neurodegenerative diseases. We analyzed SIRT1's association with chronic inflammation in dementia as an age-related neurodegenerative condition through Toll-like receptor 4 (TLR4) and interleukin-7 (IL7) for the first time. In the present study, we observed a significant increase in the level of SIRT1 in patients with all types of dementia. Interestingly, the level of TLR4 protein was significantly lower in only the patients with Alzheimer's disease (AD) compared to the healthy elderly subjects. There was no significant change in the level of IL7 between the diseased and healthy elderly subjects. A significant positive correlation between SIRT1 level and age in healthy elderly subjects was evident according to Pearson's correlation test. However, this correlation was not observed in the dementia patients. Furthermore, the positive correlation between the levels of IL7 and TLR4 in the healthy elderly subjects was absent in the dementia patients. However, there was no direct association between the examined single nucleotide polymorphisms (SNPs) and dementia at the molecular level. According to logistic regression analysis, dementia risk increases 1.16 times due to an increase in the SIRT1 level and 24.23 times due to a decrease in the TLR4 level. Interestingly, a high level in the total antioxidant status (TAS) increases the risk of dementia approximately 33.32 times. Therefore, the current study, for the first time, provides a much better molecular understanding of the interaction between decreasing TLR4 levels and increasing SIRT1 levels in dementia, especially in AD. Furthermore, it highlights the importance of epigenetics in several age-related diseases and suggests that developing novel therapies to prevent or slow down the progression of dementia may support healthy aging.
- Published
- 2018
35. MicroRNA 199a Is Downregulated in Patients After Coronary Artery Bypass Graft Surgery and Is Associated with Increased Levels of Sirtuin 1 (SIRT 1) Protein and Major Adverse Cardiovascular Events at 3-Year Follow-Up
- Author
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Ali Rıza Demir, Ulkan Kilic, Mustafa Ahmet Huyut, Yusuf Demir, Aylin Hatice Yamac, Ahmet Bacaksiz, Emre Yilmaz, Ilke Celikkale, Ramazan Ozdemir, Mehmet Erturk, Nijad Bakhshaliyev, and BAKHSALIYEV, NIJAD
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Myocardial Infarction ,Down-Regulation ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,YAMAÇ A. H. , HUYUT M. A. , Yilmaz E., ÇELİKKALE İ., BACAKSIZ A., Demir Y., Demir A. R. , Erturk M., Bakhshaliyev N., ÖZDEMİR R., et al., -MicroRNA 199a Is Downregulated in Patients After Coronary Artery Bypass Graft Surgery and Is Associated with Increased Levels of Sirtuin 1 (SIRT 1) Protein and Major Adverse Cardiovascular Events at 3-Year Follow-Up-, MEDICAL SCIENCE MONITOR, cilt.24, ss.6245-6254, 2018 ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Sirtuin 1 ,Downregulation and upregulation ,medicine ,Humans ,cardiovascular diseases ,Myocardial infarction ,Coronary Artery Bypass ,Adverse effect ,Stroke ,Aged ,biology ,business.industry ,Myocardium ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,MicroRNAs ,surgical procedures, operative ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Heart failure ,biology.protein ,Female ,business ,Follow-Up Studies ,Artery - Abstract
BACKGROUND The cardioprotective protein SIRT1 is elevated in patients with coronary artery disease (CAD) to compensate for the disease-related adverse effects, but less is known about the prognostic role of SIRT 1 regulating microRNAs in patients after coronary artery bypass graft (CABG) surgery. MATERIAL AND METHODS The expression of the SIRT 1-specific microRNAs miR-199a and miR-195 was analyzed using real-time PCR in 68 patients referred for CABG surgery and 34 control patients undergoing heart valve surgery. In CABG patients, major adverse cardiac and cerebrovascular events (MACCEs), including all-cause death, myocardial infarction (MI), re-vascularization, heart failure symptoms ≥NYHA II, re-hospitalization for any cardiovascular reason, and stroke, were analyzed at a median follow-up (FU) of 3.2 years (range: 3.0-3.6). RESULTS The level of miR-199a in patients with CAD was significantly reduced compared to the control group (relative expression: 0.89±0.49 vs. 1.90±0.90, p=0.001), while SIRT 1 protein was markedly enhanced (p
- Published
- 2018
36. Thymoquinone administration ameliorates Alzheimer's disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta
- Author
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Birsen, Elibol, Merve, Beker, Sule, Terzioglu-Usak, Tugce, Dalli, and Ulkan, Kilic
- Subjects
Neurons ,Amyloid beta-Peptides ,Cell Survival ,MAP Kinase Signaling System ,Hippocampus ,Peptide Fragments ,Rats, Sprague-Dawley ,Disease Models, Animal ,Neuroprotective Agents ,Gene Expression Regulation ,Alzheimer Disease ,Memory ,Acetylcholinesterase ,Benzoquinones ,Animals ,Female ,Phosphorylation ,Maze Learning - Abstract
Thymoquinone (TQ), a biologically active ingredient of Nigella sativa, has anti-inflammatory, anti-oxidative and neuroprotective properties. Therefore, it could be a good candidate in the recovery of Alzheimer`s disease (AD) pathology rather than current symptomatic reliefs.In the present study, we examined the molecular healing effects of TQ in amyloid beta 1-42 (AβA micro-osmotic pump containing aggregated AβThe memory performance of rats was determined by Morris water maze test. Afterwards, the acetylcholinesterase (AChE) level were measured by ELISA. Histopathological examinations of hippocampal tissue were performed for cell survival by Nissl staining, for detection of amyloid plaque deposits by Congo red staining and for determination of degenerating neurons by Fluoro Jade C staining. MicroRNA/mRNA levels and protein expressions of AD-related genes and proteins were analyzed by Real-Time Polymerase Chain Reaction and Western Blotting, respectively.Administration of TQ enhanced the memory performance of AβTQ has the capacity to recover the neuropathology by removing Aβ plaques and by restoring neuron viability. All might have established the molecular basement of the consolidation in the memory observed by means of TQ treatment.
- Published
- 2019
37. Both activation and inhibition of SIRT1 may act via exosomal GSK3α/β in the in vitro amyloid beta toxicity model
- Author
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Rabia Kalkan, N Gunay, Bahar Sarikamis, Ulkan Kilic, Birsen Elibol, and ELİBOL, BİRSEN
- Subjects
biology ,Amyloid beta ,Chemistry ,Toxicity ,General Engineering ,biology.protein ,Elibol B., -Both activation and inhibition of SIRT1 may act via exosomal GSK3α/β in the in vitro amyloid beta toxicity model-, Advances in Clinical Toxicology, cilt.4, no.175, ss.1-8, 2019 ,Pharmacology ,In vitro - Published
- 2019
38. Neutrophil Elastase Inhibitor Increases Flap Survival in Experimental Degloving Injuries
- Author
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Fatih Irmak, Erkan Yüce, Medeni Volkan Kıyak, Semra Karsidag, Kemalettin Yildiz, Kamuran Zeynep Sevim, Dağhan Dağdelen, Ulkan Kilic, YILDIZ, KEMALETTİN, and KKÜ
- Subjects
ischemia reperfusion injury ,Degloving ,Necrosis ,TUNEL assay ,biology ,business.industry ,Degloving injury ,Sivelestat ,neutrophil elastase inhibitor ,General Medicine ,medicine.disease ,Pentoxifylline ,Sepsis ,chemistry.chemical_compound ,chemistry ,Anesthesia ,Neutrophil elastase ,Edema ,medicine ,biology.protein ,medicine.symptom ,business ,medicine.drug ,Original Research - Abstract
Dagdelen, Daghan/0000-0002-2523-9195 WOS:000542499100006 PubMed: 32617053 Objectives: Degloving hand injuries have generally been viewed as among the most difficult of injuries to manage due to the extensive nature of associated damage. The traditional approach to the circumferentially degloved segment of problematic flap viability has been to resuture the flap and to wait and see. However, the waiting period or the specific hemorheological protocol remains uncertain. This study aims to acknowledge if Sivelestat, known to ameliorate ischemia-reperfusion injury, enhances the survival of avulsed flaps in a hind limb degloving model of rats and to compare Sivelestat's effects to Pentoxifylline. Methods: In this study, total flap area (cm2), area of necrosis in the flap (cm(2)), and the ratio between the necrotic and total areas (percentage) were determined. Angiogenesis among the groups was documented with CD31, anti-PECAM staining. TUNEL assay was performed to allow the visualization of cell nuclei containing fragmented DNA, a typical feature of apoptosis. Results: The findings obtained in this study showed that Sivelestat administered at 10 mg/kg/hour dosage will inhibit the ischemia-reperfusion injury more pertinently than Pentoxifylline, which exerts only hemorheological effects. Conclusion: The anti-inflammatory effects of Sivelestat will be beneficial for decreasing the early complications of degloving injury, such as inflammation, sepsis, and edema, better than Pentoxifylline, which exerts only hemorheological effects.
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- 2018
39. Therapeutic role of rifampicin in Alzheimer's disease
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Ulkan Kilic, Burak Yulug, Lutfu Hanoglu, Mehmet Ozansoy, Dogan Isık, Wolf Rüdiger Schäbitz, and Ertugrul Kilic
- Subjects
0301 basic medicine ,Nootropic Agents ,business.industry ,General Neuroscience ,General Medicine ,Disease ,medicine.disease ,Neuroprotection ,03 medical and health sciences ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Neuroimaging ,Clinical evidence ,polycyclic compounds ,medicine ,Cholinergic ,Neurology (clinical) ,Alzheimer's disease ,business ,Neuroscience ,030217 neurology & neurosurgery ,Rifampicin ,medicine.drug - Abstract
Rifampicin exerts significant brain protective functions in multiple experimental models. Here we summarize the underlying mechanisms of the neuroprotective and pro-cognitive effects of rifampicin that are mediated by its anti-inflammatory, anti-tau, anti-amyloid, and cholinergic effects. Beyond suggesting that rifampicin shows strong brain protective effects in preclinical models of Alzheimer's disease, we also provide substantial clinical evidence for the neuroprotective and pro-cognitive effects of rifampicin. Future neuroimaging studies combined with clinical assessment scores are the following steps to be taken in this field of research.
- Published
- 2018
40. Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on experimental wound healing
- Author
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K Koroglu, Hanefi Özbek, Ozlem Gok, Y Gunal, Şule Ayla, Ulkan Kilic, Bircan Kolbasi, Ayşe Arzu Şakul, and İlknur Keskin
- Subjects
Male ,medicine.medical_specialty ,Histology ,Foeniculum ,Pharmacology ,01 natural sciences ,law.invention ,Rats, Sprague-Dawley ,Terpene ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Microscopy, Electron, Transmission ,law ,Cyclohexenes ,Oils, Volatile ,medicine ,Animals ,Foeniculum Vulgare ,Olive Oil ,Essential oil ,Skin ,Wound Healing ,Limonene ,Camphanes ,integumentary system ,biology ,Plant Extracts ,Terpenes ,Granulation tissue ,Fenchone ,General Medicine ,biology.organism_classification ,Immunohistochemistry ,Norbornanes ,Essential Oil ,Rats ,0104 chemical sciences ,Surgery ,010404 medicinal & biomolecular chemistry ,Medical Laboratory Technology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Histopathology ,Wound healing - Abstract
We investigated the wound healing efficacy of the Foeniculum vulgare compounds, fenchone and limonene, using an excisional cutaneous wound model in rats. An excision wound was made on the back of the rat and fenchone and limonene were applied topically to the wounds once daily, separately or together, for 10 days. Tissue sections from the wounds were evaluated for histopathology. The healing potential was assessed by comparison to an untreated control group and an olive oil treated sham group. We scored wound healing based on epidermal regeneration, granulation tissue thickness and angiogenesis. After day 6, wound contraction with limonene was significantly better than for the control group. Ten days after treatment, a significant increase was observed in wound contraction and re-epithelialization in both fenchone and limonene oil treated groups compared to the sham group. Groups treated with fenchone and with fenchone + limonene scored significantly higher than the control group, but the difference was not statistically significant compared to the olive oil treated group. Our findings support the beneficial effects of fenchone and limonene for augmenting wound healing. The anti-inflammatory and antimicrobial activities of fenchone and limonene oil increased collagen synthesis and decreased the number of inflammatory cells during wound healing and may be useful for treating skin wounds.
- Published
- 2017
41. Topikal lipozomal resveratrolün insizyonal ve eksizyonal yara iyileşme sürecine etkileri
- Author
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Erdem Yesilada, Ekrem Musa Özdemir, Ahmet Burak Çağlayan, Ulkan Kilic, Nejda Bedri, Şule Ayla, Mustafa Çağlar Beker, Mehmet Yalçın Günal, İsmail Aslan, ALKÜ, and 0-belirlenecek
- Subjects
medicine.medical_specialty ,Liposome ,Excisional wound ,integumentary system ,Lipozom ,business.industry ,Dermatology ,Resveratrol ,lcsh:RL1-803 ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,Surgery ,chemistry.chemical_compound ,chemistry ,Insizyonal Yara ,liposome ,medicine ,lcsh:Dermatology ,Eksenel Çekme-Uzama Testleri ,incisional wound ,axial tensile-elongation tests ,Eksizyonal Yara ,business ,excisional wound ,resveratol - Abstract
Background and Design: The objective of this study was to investigate the wound healing activity of different concentrations of liposomal trans-resveratrol formulations on incisional and excisional wounds in rats. Materials and Methods: The wound healing effect was tested by an excisional and incisional wound model. Wound closure was measured for 12 days. On the 12th day of the study, maximal load, maximum stress, stress, and % of elongation values were evaluated in the incisional wound. In addition, angiogenesis, granulation tissue thickness, epidermal and dermal regeneration values, and macroscopic photographic analyses were evaluated in the excisional wound. Results: When the wound tissue surface healing rates were evaluated, similar effects were observed at the end of the 10th and 12th days between the 5% Res group and the commercial product containing 1% Centella asiatica extract used as the reference molecule. Histological evaluation showed that 1% Res and 5% Res groups induced significant wound healing activity compared to the control group. Furthermore, 1% Res and 5% Res groups increased wound healing rates by promoting granulation tissue, epidermal, and dermal regeneration as well as angiogenesis. Conclusion: Liposomal formulations containing 1% and 5% resveratrol were found to have positive effects on the healing process, both on excisional and incisional wound tissues. Amaç: Bu çalışmanın amacı, sıçanlarda insizyonel ve eksizyonel yaralar üzerine farklı konsantrasyonlarda hazırlanmış lipozomal trans-resveratrol formülasyonlarının yara iyileşme aktivitesi üzerine etkinliğini araştırmaktır. Gereç ve Yöntem: Yara iyileşme etkisi, eksizyonel ve insizyonel yara modeli kullanılarak test edildi. Yara yüzey alanları 12 gün süresince ölçüldü. Çalışmanın 12. gününde, insizyonel yaralarda maksimum yük, maksimum stres, gerginlik (strain) ve % uzama değerleri değerlendirildi. Ek olarak, eksizyonel yaralarda anjiyogenez, granülasyon dokusu kalınlığı, epidermal ve dermal rejenerasyon değerleri ve makroskopik fotoğraf analizleri değerlendirildi. Bulgular: Yara dokusu yüzey iyileşme oranları değerlendirildiğinde, %5 Res grubu ile referans molekül olarak kullanılan 1% Centella asiatica ekstresi arasında 10. ve 12. günlerde benzer etkiler gözlendi. Histolojik değerlendirme, %1 Res ve %5 Res gruplarının kontrol grubuna kıyasla anlamlı yara iyileşme aktivitesi oluşturduğunu gösterdi. Ayrıca, %1 Res ve %5 Res grupları, granülasyon dokusu, epidermal ve dermal rejenerasyonun yanı sıra anjiyogenezi uyararak yara iyileşme oranlarını arttırdı. Sonuç: %1 ve %5 resveratrol içeren lipozomal formülasyonların, hem eksizyonel hem de insizyonel yara dokularında iyileşme süreci üzerinde olumlu etkileri olduğu bulunmuştur.
- Published
- 2019
42. A different view on the platelet aggregation inhibitor clopidogrel - a well-suitable anti-oedema agent in a preclinical model of brain injury?
- Author
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Berrak Calglayan, Mehmet Ozansoy, Ulkan Kilic, Burak Yulug, Mehmet Yalçın Günal, Ertugrul Kilic, İlknur Keskin, ALKÜ, Fakülteler, Sağlık Bilimleri Fakültesi, Fizyoterapi ve Rehabilitasyon Bölümü, and Günal, M. Yalçın
- Subjects
brain swelling ,Objem İnfarktu ,Pharmacology ,infarct volume ,Neuroprotektivní Účinek ,cell survival pathways ,medicine ,Cell Survival Pathways ,Poranění Mozku ,cardiovascular diseases ,Brain Injury ,clopidogrel ,Brain Swelling ,business.industry ,Clopidogrel ,brain injury ,neuroprotective effect ,Neuroprotective Effect ,Infarct Volume ,Platelet aggregation inhibitor ,Surgery ,Mechanizmy Přežití Buněk ,Neurology (clinical) ,Klopidogrel ,business ,Otok Mozku ,medicine.drug ,circulatory and respiratory physiology - Abstract
Aim: The neuroprotective effects of clopidogrel have already been shown in various experimental models. Taking into account the fact that clopidogrel is well tolerated and approved for use in various clinical settings, it can be an attractive candidate for further clinical investigations, especially when the anti-oedema effect appears to be a reasonable adjuvant strategy, such as in brain injury (BI). Here we aimed to examine the neuroprotective role of clopidogrel in BI. Methods: To investigate the effects of clopidogrel, we induced BI in mice using a cold trauma model and evaluated the underlying cell survival/death mechanisms via cresyl violet, TUNEL staining and western blot analysis. Results: Clopidogrel at a dose of 3 mg/kg led to a significant reduction in brain swelling. Similar decreases were observed with 10 mg/kg and 30 mg/kg of clopidogrel. We also have shown that clopidogrel blocks the prominent inflammatory injury pathways and exerts a significant anti-apoptotic effect (3 and 30 mg/kg), which has boon associated with increased neuronal cell survival pathways. Clopidogrel (3, 10 and 30 mg/kg) dose-dependently altered the JNK, p-38, AKT, ERK and p53 levels. Conclusion: Our findings demonstrate that clopidogrel can be a novel candidate for the reduction of post-traumatic BI and oedema. We propose that it can be applied mainly in the acute phases of cerebral ischaemia, which is characterized by haemorrhagic transformation and brain oedema. Cíl: Neuroprotektivní účinky klopidogrelu již byly prokázány na různých experimentálních modelech. Vzhledem k tomu, že klopidogrel je dobře tolerován a schválen k používání v různých klinických podmínkách, může být atraktivním kandidátem pro další klinická zkoumání, zejména v situaci, kdy se antiedematický účinek jeví jako vhodná adjuvantní strategie, například při poranění mozku. Naším záměrem bylo prozkoumat neuroprotektivní roli klopidogrelu při poranění mozku. Metody: Pro zkoumání účinků klopidogrelu jsme navodili poranění mozku s použitím modelu chladového traumatu u myší a zkoumali jsme základní mechanizmus přežití/odumírání buněk s použitím kresolové violeti, barvení TUNEL a analýzy western blot. Výsledky: Klopidogrel v dávce 3 mg/kg vedl k signifi kantnímu snížení otoku mozku. Podobný pokles byl pozorován při dávce klopidogrelu 10 mg/kg a 30 mg/kg. Rovněž jsme prokázali, že klopidogrel blokoval prominentní cesty poškození zánětem a vykazoval silný antiaptotický účinek (3 a 30 mg/kg), který byl spojen se zvýšenou možností přežití neuronových buněk. Klopidogrel (3, 10 a 30 mg/kg) měnil dávkově dependentním způsobem hladiny JNK, p-38, AKT, ERK a p53. Závěr: Naše nálezy prokazují, že klopidogrel může být novým kandidátem pro zmírnění posttraumatického poranění mozku a edému. Domníváme se, že může být aplikován hlavně v akutních fázích cerebrální ischemie, která je charakterizována hemoragickou transformací a edémem mozku.
- Published
- 2019
43. Thymoquinone administration ameliorates Alzheimer's disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta1–42 infused rat model
- Author
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Birsen Elibol, Merve Beker, Tugce Dalli, Sule Terzioglu-Usak, Ulkan Kilic, and ELİBOL, BİRSEN
- Subjects
Amyloid beta ,Pharmaceutical Science ,Morris water navigation task ,Pharmacology ,Hippocampal formation ,Neuroprotection ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,0302 clinical medicine ,Drug Discovery ,Hippocampus (mythology) ,Thymoquinone ,030304 developmental biology ,ELİBOL B., Beker M., Terzioglu-Usak S., Dalli T., Kilic U., -Thymoquinone administration ameliorates Alzheimer-s disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta(1-42) infused rat model-, PHYTOMEDICINE, cilt.79, 2020 ,0303 health sciences ,biology ,Chemistry ,Dentate gyrus ,Complementary and alternative medicine ,030220 oncology & carcinogenesis ,Nissl body ,symbols ,biology.protein ,Molecular Medicine - Abstract
Background Thymoquinone (TQ), a biologically active ingredient of Nigella sativa, has anti-inflammatory, anti-oxidative and neuroprotective properties. Therefore, it could be a good candidate in the recovery of Alzheimer`s disease (AD) pathology rather than current symptomatic reliefs. Purpose In the present study, we examined the molecular healing effects of TQ in amyloid beta 1–42 (Aβ1–42) peptide-infused AD rat hippocampus. Study design A micro-osmotic pump containing aggregated Aβ1–42 was cannulated into the hippocampus of adult female rats. After two weeks infusion, the dose of TQ (10 mg/kg or 20 mg/kg) was determined according to the HPLC results of cerebrospinal fluid and TQ was given to rats intragastrically for 15 days. Methods The memory performance of rats was determined by Morris water maze test. Afterwards, the acetylcholinesterase (AChE) level were measured by ELISA. Histopathological examinations of hippocampal tissue were performed for cell survival by Nissl staining, for detection of amyloid plaque deposits by Congo red staining and for determination of degenerating neurons by Fluoro Jade C staining. MicroRNA/mRNA levels and protein expressions of AD-related genes and proteins were analyzed by Real-Time Polymerase Chain Reaction and Western Blotting, respectively. Results Administration of TQ enhanced the memory performance of Aβ1–42 infused rats and it also ameliorated the neuronal loss in the cornu ammonis (CA1), but not in the dentate gyrus (DG). In addition, TQ treatment decreased the fibril deposition whose accumulation was significantly higher in the Aβ1–42-infused animals compared to that of the control group. The expression profiles of mir29c and Bax which significantly upregulated in the Aβ1–42-infused animals were attenuated by TQ. Furthermore, administration of TQ decreased the expressions of Aβ, phosphorylated-tau, and BACE-1 proteins. There was no significant therapeutic effect of TQ on the AKT/GSK3β or MAPK signaling pathways which were affected due to Aβ1–42 infusion. Conclusion TQ has the capacity to recover the neuropathology by removing Aβ plaques and by restoring neuron viability. All might have established the molecular basement of the consolidation in the memory observed by means of TQ treatment.
- Published
- 2020
44. Targeting different pathophysiological events after traumatic brain injury in mice: Role of melatonin and memantine
- Author
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Reyhan Zeynep Gundogdu, Ahmet Burak Çağlayan, Taha Kelestemur, Berrak Caglayan, Mustafa Çağlar Beker, Ulkan Kilic, Ertugrul Kilic, Burak Yulug, and Esra Yalcin
- Subjects
Brain Infarction ,Male ,0301 basic medicine ,Traumatic Brain Injury ,Traumatic brain injury ,DNA fragmentation ,Pharmacology ,Neuroprotection ,Melatonin ,03 medical and health sciences ,0302 clinical medicine ,Memantine ,medicine ,Animals ,Mice, Inbred BALB C ,business.industry ,General Neuroscience ,Glutamate receptor ,Brain ,Free Radical Scavengers ,medicine.disease ,Free radical scavenger ,Neuroprotective Agents ,030104 developmental biology ,Traumatic injury ,Brain Injuries ,NMDA receptor ,business ,Neuroscience ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,medicine.drug - Abstract
WOS: 000369471900016 PubMed ID: 26639427 The tissue damage that emerges during traumatic brain injury (TBI) is a consequence of a variety of pathophysiological events, including free radical generation and over-activation of N-methyl-D-aspartate-type glutamate receptors (NMDAR). Considering the complex pathophysiology of TBI, we hypothesized that combination of neuroprotective compounds, targeting different events which appear during injury, may be a more promising approach for patients. In this context, both NMDAR antagonist memantine and free radical scavenger melatonin are safe in humans and promising agents for the treatment of TBI. Herein, we examined the effects of melatonin administered alone or in combination with memantine on the activation of signaling pathways, injury development and DNA fragmentation. Both compounds reduced brain injury moderately and the density of DNA fragmentation significantly. Notably, melatonin/memantine combination decreased brain injury and DNA fragmentation significantly, which was associated with reduced p38 and ERK-1/2 phosphorylation. As compared with melatonin and memantine groups, SAM/INK-1/2 phosphorylation was also reduced in melatonin/memantine combined animals. In addition, melatonin, memantine and their combination decreased iNOS activity significantly. Here, we provide evidence that melatonin/memantine combination protects brain from traumatic injury, which was associated with decreased DNA fragmentation, p38 phosphorylation and iNOS activity. EMBO (European Molecular Biology Organization); Turkish Academy of Sciences (TUBA) This work was supported by EMBO (European Molecular Biology Organization) installation grant and Turkish Academy of Sciences (TUBA).
- Published
- 2016
45. High Levels of SIRT1 Expression as a Protective Mechanism Against Disease-Related Conditions
- Author
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Ulkan Kilic, Birsen Elibol, and ELİBOL, BİRSEN
- Subjects
0301 basic medicine ,Damp ,Mini Review ,Endocrinology, Diabetes and Metabolism ,SIRT1 expression ,Regulator ,Context (language use) ,Disease ,Bioinformatics ,metabolic diseases ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,Endocrinology ,Medicine ,oxidative stress ,neurodegenerative diseases ,Epigenetics ,lcsh:RC648-665 ,biology ,business.industry ,Mechanism (biology) ,Neurodegeneration ,food and beverages ,medicine.disease ,cardiovascular diseases ,enzymes and coenzymes (carbohydrates) ,030104 developmental biology ,Elibol B., KILIC U., -High Levels of SIRT1 Expression as a Protective Mechanism Against Disease-Related Conditions.-, Frontiers in endocrinology, cilt.9, ss.614, 2018 ,Sirtuin ,biology.protein ,business - Abstract
SIRT1 protein, a member of Silent Information Regulator 2 (Sir2) protein family, have gained considerable attention as epigenetic regulators for a great area in the human physiology. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, cardiovascular diseases, cancer and neurodegeneration. Here, we provide an overview of the association of the increasing level of SIRT1 protein for regulating some disease related conditions such as obesity, cardiovascular diseases and neurodegeneration. This review also provides a detailed molecular understanding of the interaction of the some basic molecules with increasing SIRT1 levels rather than reduction of the SIRT1 expression. In this context, the current approaches to enhancing the expression of SIRT1 points the importance of epigenetics in several age-related diseases to provide a healthy aging by developing novel therapies which can prevent or damp the progression of some diseases.
- Published
- 2018
46. Role of erythropoietin and its receptor in the development of endometriosis in rats
- Author
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Mehmet Ozansoy, Cenk Ersavas, Ekrem Musa Özdemir, Ulkan Kilic, İsmail Aslan, Ertugrul Kilic, İlknur Keskin, Zehra Eren, Mehmet Yalçın Günal, ALKÜ, 0-belirlenecek, Günal, M.Y., Ozansoy, M., Kılıç, Ü., Keskin, İ., Özdemir, E.M., Aslan, İ., Kılıç, E., Yeditepe Üniversitesi, Gunal, Mehmet Yalcin Alanya Alaaddin Keykubat Univ, Sch Med, Dept Physiol, Antalya, Turkey, Ozansoy, Mehmet, Kilic, Ertugrul Istanbul Medipol Univ, Sch Med, Dept Physiol, Istanbul, Turkey, Kilic, Ulkan Univ Hlth Sci, Sch Med, Dept Med Biol, Istanbul, Turkey, Keskin, Ilknur Istanbul Medipol Univ, Sch Med, Dept Histol & Embryol, Istanbul, Turkey, Ozdemir, Ekrem Musa Istanbul Medipol Univ, Expt Anim Ctr, Istanbul, Turkey, Aslan, Ismail Yeditepe Univ, Sch Pharm, Dept Pharmaceut Technol, Istanbul, Turkey, Eren, Zehra Yeditepe Univ, Sch Med, Dept Nephrol, Istanbul, Turkey, Ersavas, Cenk Istanbul Medipol Univ, Sch Med, Dept Gen Surg, Istanbul, Turkey, Gunal, Mehmet Yalcin, Kilic, Ulkan, Keskin, Ilknur, Ersavas, Cenk, Kilic, Ertugrul Istanbul Medipol Univ, Regenerat & Restorat Med Res Ctr REMER, Istanbul, Turkey, OZDEMIR, EKREM MUSA -- 0000-0001-9416-7757, Aslan, Ismail -- 0000-0001-7075-7103, gunal, mehmet yalcin -- 0000-0001-7702-2441, and Kilic, Ertugrul -- 0000-0001-6494-8923
- Subjects
endometriosis ,medicine.medical_specialty ,Stromal cell ,mircera ,Endometriosis ,lcsh:Medicine ,lcsh:Gynecology and obstetrics ,Receptor activator ,Lesion ,Abdominal wall ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,MIRCERA ,Receptor ,Erythropoietin ,lcsh:RG1-991 ,Original Investigation ,Activator (genetics) ,business.industry ,lcsh:R ,receptor activator ,Obstetrics and Gynecology ,medicine.disease ,Darbepoietin ,Haematopoiesis ,Endocrinology ,medicine.anatomical_structure ,darbepoietin ,erythropoietin ,medicine.symptom ,business ,030215 immunology ,medicine.drug - Abstract
Objective: Besides its hematopoietic function, erythropoietin (EPO) may protect tissues from degenerative disorders. As such, EPO and its receptors were revealed in nonhematopoietic cells, including stromal and endometrial epithelial cells. However, the role of EPO in endometrial disorders is still unknown. Here, we aimed to examine the role of EPO and its receptor activation in the development of endometriosis in rats. Material and Methods: Animals were treated with EPO, darbepoietin (the synthetic form of EPO) or EPO’s receptor activator, methoxy polyethylene glycol-epoetin beta (MIRCERA), after development of endometriosis. Endometriosis was induced by estrogen-administration following surgical attachment of endometrial surface on the inner abdominal wall. Treatments were started 3 weeks after induction of endometriosis and continued for the following 3 weeks. For the analysis of recurrence of endometriosis, additional analyses were conducted 3 weeks after cessation of treatments. Results: As compared with vehicle-treated animals, lesion size was reduced significantly and recurrence of endometriosis was not observed in all treatment groups. Histopathologic examination revealed that EPO and darbepoietin were more effective than MIRCERA- and vehicle-treated animals. Conclusion: Here we provide evidence that EPO is a promising candidate for the treatment of endometriosis. Our histopathologic results in particular indicate that EPO is more effective than its receptor activator MIRCERA in the development endometriosis. © 2019 by the Turkish-German Gynecological Education and Research Foundation. Türkiye Bilimler Akademisi Acknowledgements: This work was funded by Turkish Academy of Sciences (TUBA). We would like to thank to Laboratory Technician Nurhayat Dönek from Bezmialem University for help throughout this research.
- Published
- 2018
47. N-acetylcysteine suppresses colistimethate sodium-induced nephrotoxicity via activation of SOD2, eNOS, and MMP3 protein expressions
- Author
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Yasemin Yozgat, Cilem Ercan, Mehmet Ozansoy, Ulkan Kilic, Turan Aslan, Bahadir Ceylan, Pelin Yildiz, and YILDIZ, PELİN
- Subjects
Male ,0301 basic medicine ,Antioxidant ,Ceylan B., Ozansoy M., Kılıç Ü., Yozgat Y., Ercan Ç., Yıldız P., Aslan T., -N-acetylcysteine suppresses colistimethate sodium-induced nephrotoxicity via activation of SOD2, eNOS, and MMP3 protein expressions.-, Renal failure, cilt.40, ss.423-434, 2018 ,Nitric Oxide Synthase Type III ,medicine.medical_treatment ,030106 microbiology ,SOD2 ,Pharmacology ,lcsh:RC870-923 ,Kidney ,Critical Care and Intensive Care Medicine ,Nephrotoxicity ,Acetylcysteine ,03 medical and health sciences ,Enos ,Laboratory Study ,Acetylglucosaminidase ,Animals ,Humans ,Medicine ,Rats, Wistar ,reactive oxygen species ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Colistin ,Superoxide Dismutase ,business.industry ,nephrotoxicity ,rat model ,Free Radical Scavengers ,General Medicine ,Acute Kidney Injury ,lcsh:Diseases of the genitourinary system. Urology ,biology.organism_classification ,Rats ,Disease Models, Animal ,chemistry ,Nephrology ,Creatinine ,Matrix Metalloproteinase 3 ,business ,medicine.drug ,Colistimethate - Abstract
WOS: 000439906200002 PubMed ID: 30035652 Objective: To investigate the molecular mechanisms of colistimethate sodium-induced nephrotoxicity and the protective effect of N-acetylcysteine (NAC) against nephrotoxicity.Methods: Twenty-eight Wistar rats were divided into four groups comprised of control, colistin, NAC, and colistin-NAC co-treatment, respectively. Serum creatinine and urine N-acetyl--d-glucosaminidase (NAG) levels were measured at different time intervals. Histological changes, apoptosis, total oxidant and antioxidant status, and the expression levels of endothelial nitric oxide synthase (eNOS), superoxide dismutase 2 (SOD2), and matrix metalloproteinase 3 (MMP3) were evaluated in renal tissue.Results: In the colistin group, post-treatment creatinine levels were higher than pretreatment levels (p=.001). There was a significant increase in urine NAG level following colistin treatment on day 10, compared to the baseline value and the first day of treatment (p=.001 and .0001, respectively). Urine NAG levels were higher in the colistin group on the 10th day of treatment than in the other groups (p
- Published
- 2018
48. Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease
- Author
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Ozlem Gok, Hakan Senturk, Yusuf Kayar, Birol Baysal, Ulkan Kilic, Omer Uysal, Ali Tüzün Ince, Venkatanarayana Gangarapu, and ŞENTÜRK, HAKAN
- Subjects
Male ,Lipopolysaccharides ,Biopsy ,Antibiotics ,Body Mass Index ,chemistry.chemical_compound ,Anti-Infective Agents ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Nonalcoholic fatty liver disease ,Prospective Studies ,Gut Microbiota ,biology ,medicine.diagnostic_test ,Gastroenterology ,Alanine Transaminase ,Middle Aged ,Rifamycins ,Treatment Outcome ,Cytokines ,Female ,Adult ,Adolescent ,Nonalcoholic Fatty Liver Disease ,medicine.drug_class ,Sensitivity and Specificity ,Rifaximin ,Proinflammatory cytokine ,Predictive Value of Tests ,Diabetes mellitus ,medicine ,Humans ,In patient ,Aspartate Aminotransferases ,Aged ,Hepatology ,business.industry ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Endotoxins ,Diabetes Mellitus, Type 2 ,chemistry ,Immunology ,Gangarapu V., Ince A., Baysal B., Kayar Y., Kılıç U., Gök Ö., Uysal Ö., Şenturk H., -Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease.-, European journal of gastroenterology & hepatology, cilt.27, ss.840-5, 2015 ,business ,Biomarkers ,Bacteria - Abstract
WOS: 000356588500012 PubMed ID: 26043290 ObjectiveRecent studies have suggested that endotoxin-induced cytokines play an important role in nonalcoholic fatty liver disease (NAFLD). Rifaximin is a nonabsorbable antibiotic that might act on Gram-negative bacteria, thereby inhibiting endotoxin proinflammatory cytokine production in patients with NAFLD. Our aim was to investigate the efficacy of rifaximin on NAFLD.MethodsForty-two patients with biopsy-proven NAFLD [15 steatosis, 27 nonalcoholic steatohepatitis (NASH)] were included in this prospective, open-label, observational cohort study. BMI and serum aspartate aminotransferase, alanine aminotransferase (ALT), gamma glutamyl transferase, lipid profile, ferritin, C-reactive protein, glucose, insulin, homeostatic model assessment as well as endotoxin, serum Toll-like receptor 4 (TlR4), interleukin-1 (IL-1), IL-6, IL-10, IL-12, and tumor necrosis factor- (TNF-) levels were measured before and after a 28-day administration of rifaximin (1200mg/daily). Results were analyzed using nonparametric Wilcoxon signed-rank tests.ResultsA mild reduction in the mean BMI (32.36.9 vs. 31.9 +/- 6.8, P=0.02) and a significant reduction in the endotoxin (0.9 +/- 0.34 vs. 0.8 +/- 0.13, P=0.03) and IL-10 (4.08 +/- 0.9 vs. 3.73 +/- 0.7, P=0.006) levels in the NASH group were noted. A significant reduction was observed in serum aspartate aminotransferase (50.4 +/- 39 vs. 33 +/- 14, P=0.01), ALT (72 +/- 48 vs. 45.2 +/- 26.3, P=0.0001), gamma glutamyl transferase (52 +/- 33 vs. 41.2 +/- 21.1, P=0.02), LDL (137 +/- 34 vs. 127 +/- 27.5, P=0.03), and ferritin (142 +/- 214 vs. 89.3 +/- 123, P=0.0001) in the NASH group, but only in ALT (50.4 +/- 26 vs. 35.5 +/- 23.25, P=0.01), and ferritin (73.6 +/- 83 vs. 55 +/- 76, P=0.004) levels decreased significantly in the steatosis group. Treatment with rifaximin did not exert a significant effect on serum levels of TLR-4, IL-1, IL-6, IL-12, or TNF- in either group.ConclusionIn NAFLD and especially in NASH, short-term administration of rifaximin appears to be safe and effective. Scientific Research Project Council of the Bezmialem Vakif University (BAP) [6.2013/4] This work is supported by the Scientific Research Project Council of the Bezmialem Vakif University (BAP No. 6.2013/4)
- Published
- 2015
49. Changes in expression of Slit1 and its receptor Robo2 in trigeminal ganglion and inferior alveolar nerve following inferior alveolar nerve axotomy in adult rats: a pilot study
- Author
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Feti Tulubas, Ümit Şener, Adnan Yüksek, Ahmet Mihmanli, Mehmet Ceber, Ulkan Kilic, and M.A. Durak
- Subjects
Electrophoresis ,Time Factors ,Mandibular Nerve ,medicine.medical_treatment ,Blotting, Western ,Nerve Tissue Proteins ,Pilot Projects ,Stimulation ,Inferior alveolar nerve ,Rats, Sprague-Dawley ,Trigeminal ganglion ,SLIT1 ,medicine ,Animals ,Receptors, Immunologic ,Receptor ,Jaw opening reflex ,business.industry ,Sham surgery ,Axotomy ,Nerve Regeneration ,Rats ,a pilot study-, INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, cilt.44, ss.518-527, 2015 [Ceber M., Mihmanli A., Kilic U., Sener U., Yuksek A., Durak M. A. , Tulubas F., -Changes in expression of Slit1 and its receptor Robo2 in trigeminal ganglion and inferior alveolar nerve following inferior alveolar nerve axotomy in adult rats] ,Electrophysiology ,Trigeminal Ganglion ,Otorhinolaryngology ,Anesthesia ,Surgery ,Oral Surgery ,business - Abstract
The objective of this study was to analyze changes in expression pattern of Slit1 and Robo2, and to clarify the relationship between these changes and functional recovery of the axotomized inferior alveolar nerve (IAN) without repair using a rat IAN axotomy model. Slitl and Robo2 were weakly expressed in samples taken from trigeminal ganglion (TG) and IAN of sham surgery rats. In axotomized rats, expression levels increased significantly from day 2 to day 28 post-axotomy, with peaks on days 14 (Slit1) and 7 (Robo2) after axotomy (relative to sham: Slit1 in TG P < 0.0005, Slitl in IAN P = 0.003, Robo2 in TG P < 0.0005, and Robo2 in IAN P < 0.0005). Over-expressed Slitl and Robo2 in both the TG and IANs of axotomized rats did not return to sham levels during the 28-day observation period of this study. The regeneration and functional recovery of axotomized IAN was evaluated by jaw opening reflex (JOR) recorded before and after axotomy. JOR occurrence (0% on day 7, 35% on day 14, and 85% on day 28) increased gradually, and the relative threshold of electrical stimulation eliciting JOR decreased gradually (1000.0 +/- 0.0% on day 7, 854.3 +/- 132.5% on day 14, and 302.6 +/- 92.3% on day 28). On day 28 after axotomy, JOR occurrence and the relative JOR threshold had almost returned to those of sham rats. These findings suggest that Slitl and Robo2 are involved in the regeneration and functional recovery of the axotomized IAN.
- Published
- 2015
50. HMG-CoA reductase inhibitor rosuvastatin improves abnormal brain electrical activity via mechanisms involving eNOS
- Author
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Fikrettin Şahin, M.S. Ethemoglu, Berrak Caglayan, S. Oztezcan, N. Ekimci, Ahmet Burak Çağlayan, Ulkan Kilic, Ertugrul Kilic, Ayşegül Doğan, Fatma Burcu Seker, Bayram Yilmaz, and Selami Demirci
- Subjects
HMG-CoA Reductase ,Male ,Simvastatin ,medicine.medical_specialty ,Statin ,Nitric Oxide Synthase Type III ,medicine.drug_class ,Atorvastatin ,Gene Expression ,Reductase ,Neuroprotection ,Rosuvastatin ,Capillary Permeability ,Rats, Sprague-Dawley ,Random Allocation ,Enos ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Rosuvastatin Calcium ,bcl-2-Associated X Protein ,Epilepsy ,biology ,Caspase 3 ,General Neuroscience ,Brain ,nutritional and metabolic diseases ,Penicillin G ,biology.organism_classification ,Disease Models, Animal ,Endocrinology ,Blood-Brain Barrier ,HMG-CoA reductase ,eNOS ,biology.protein ,Anticonvulsants ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Tumor Suppressor Protein p53 ,medicine.drug - Abstract
WOS: 000346243100032 PubMed ID: 25453767 Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin-treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood-brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with rosuvastatin in human epilepsy patients with hypercholesterolemia. European Molecular Biology Organization (EMBO); Turkish Academy of Sciences (TUBA/GEBIP) This work was supported by European Molecular Biology Organization (EMBO) (installation grant) and Turkish Academy of Sciences (TUBA/GEBIP).
- Published
- 2015
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