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Öğe Adaptive and terminal endoplasmic reticulum stress genes methylation levels in Parkinson patients' peripheral blood(Literatura Medica, 2025) Gemici, Yagmur Inalkac; Dundar, Muhammed; Gozukara, Harika Gozde; Koc, AhmetBackground and purpose-Misfolded protein stress has come to the fore among the molecular mechanisms that can cause degeneration. Whereas one of the most important protein of adaptive Endoplasmic Reticulum stress (ERS) is XBP1, CHOP and ASK proteins are associated with apoptosis and terminal ERS. To the best of our knowledge, methylation levels of adaptive and terminal ERS genes in Parkinson's Disease (PD) patients' blood are unknown. We aimed to evaluate if there is a difference in the DNA methylation levels of the ERS related protein-coding genes in peripheral blood of PD patients compared with healthy controls. The clinical significance of these gene methylation levels was evaluated as the second aim. Methods-DNA was isolated from the blood of PD patients (n=23) and controls (n=19). We used a methylation-specific qPCR approach to assess the methylation status of the ERS genes. The correlation between clinical findings and the methylation levels in PD patients were evaluated with appropriate statistical methods. Results-Terminal ERS related genes were statistically significantly hypomethylated in PD (ASK1 p=0.020, and CHOP p<0.001) whereas adaptive ERS gene XBP1's methylation level was not different between groups. Except for XBP1 and MMSE positive, and CHOP and depression negative correlation no correlation was found between clinical markers and methylation levels of the selected genes. (p=0.040, p=0.024), Conclusion-PD patients' peripheral blood methylation levels of adaptive and terminal ERS related genes are significantly different from healthy controls'. While XBP1 is known to be neuroprotective, CHOP and ASK are important proteins in apoptosis, and their methylation differences in peripheral blood provide a clue that they could be used as biomarkers in the future. Therefore, further biomarker and treatment studies should be conducted on these proteins and their pathways.Öğe Boron stress signal is transmitted through the TOR pathway(Elsevier Gmbh, 2023) Yilmaz, Irem Uluisik; Koc, AhmetAlthough boron is an essential element for many organisms, an excess amount of it can cause toxicity, and the mechanism behind this toxicity is not yet fully understood. The Gcn4 transcription factor plays a crucial role in the boron stress response by directly activating the expression of the boron efflux pump Atr1. More than a dozen transcription factors and multiple cell signaling pathways have roles in regulating the Gcn4 transcription factor under various circumstances. However, it is unknown which pathways or factors mediate boron signaling to Gcn4. Using the yeast Saccharomyces cerevisiae as a model, we analyzed the factors that converge on the Gcn4 transcription factor to assess their possible roles in boron stress signaling. Our findings show that the GCN system is activated by uncharged tRNA stress in response to boron treatment and that GCN1, which plays a role in transferring uncharged tRNAs to Gcn2, is necessary for the kinase activity of Gcn2. The SNF and PKA pathways were not involved in mediating boron stress, even though they interact with Gcn4. Mutations in TOR pathway genes, such as GLN3 and TOR1, abolished Gcn4 and ATR1 activation in response to boric acid treatment. Therefore, our study suggests that the TOR pathway must be functional to form a proper response against boric acid stress.Öğe Characterization of long living yeast deletion mutants that lack mitochondrial metabolism genes DSS1, PPA2 and AFG3(Elsevier, 2019) Muid, K. A.; Kimyon, Onder; Reza, Shahadat Hasan; Karakaya, Huseyin Caglar; Koc, AhmetMolecular mechanisms of aging and longevity are still mostly unknown. Mitochondria play central roles in cellular metabolism and aging. In this study, we identified three deletion mutants of mitochondrial metabolism genes (ppa2 Delta, dss1 Delta, and afg3 Delta) that live longer than wild-type cells. These long-lived cells harbored significantly decreased amount of mitochondria] DNA (mtDNA) and reactive oxygen species (ROS). Compared to the serpentine nature of wild-type mitochondria, a different dynamics and distribution pattern of mitochondria were observed in the mutants. Both young and old long-lived cells produced relatively low but adequate levels of ATP for cellular activities. The status of the retrograde signaling was checked by expression of CIT2 gene and found activated in long-lived mutants. The mutant cells were also profiled for their gene expression patterns, and genes that were differentially regulated were determined. All long-lived cells comprised similar pleiotropic phenotype regarding mitochondrial dynamics and functions. Thus, this study suggests that DSS1, PPA2, and AFG3 genes modulate the lifespan by altering the mitochondrial morphology and functions.Öğe Characterization of the BETA1 gene, which might play a role in Beta vulgaris subsp maritima salt tolerance(Tubitak Scientific & Technological Research Council Turkey, 2017) Uysal, Ozge; Cakiroglu, Cigdem; Koc, Ahmet; Karakaya, Huseyin CaglarSalinity stress has a negative impact on plant growth, which affects homeostasis and productivity. The uptake of nonessential salt ions changes the osmotic balance of the cell and causes dehydration. Higher plants develop salt tolerance mechanisms to avoid dehydration. Sea beet (Beta vulgaris subsp. maritima) is a halophytic ancestor of cultivated sugar beet that displays salt stress tolerance. In this study, we screened a B. vulgaris subsp. maritima cDNA library in Saccharomyces cerevisiae strain Ab1 1c (ena1 triangle, nha 1/4 triangle, nhx1 triangle), which is deficient in sodium transport, to find sodium-detoxifying genes. We identified a cDNA construct, named BETA 1, providing salt tolerance to yeast cells. This gene had no previously described function. Intracellular sodium measurements demonstrated no significant differences between yeast cells expressing BETA1 or a sham vector, suggesting that sodium was not effluxed in BEZA1-expressing cells. Transcriptionally, BETA1 mRNA levels were induced immediately in leaves and later in the root system in response to the salt stress. Our results suggest that the BETA1 gene is part of the salt tolerance network in B. vulgaris subsp. maritima.Öğe The Effect of Apricot Added Sports Drink on Cardiac Mitochondrial Dysfunction in High Intensity Exercising Rats(Wiley, 2023) Ozer, Muhammed Yusuf; Duzova, Halil; Gul, Mehmet; Arslan, Ozge; Elmas, Furkan; Koc, Ahmet; Durmaz, Gokhan[Abstract Not Available]Öğe Effects of central FGF21 infusion on the glucose homeostasis in rats (brain-pancreas axis)(Taylor & Francis Ltd, 2023) Tanbek, Kevser; Yilmaz, Umit; Gul, Mehmet; Koc, Ahmet; Sandal, SuleymanIntroductionGlucose homeostasis is a physiological process mediated by a variety of hormones. Fibroblast growth factor (FGF) 21 is a protein expressed in the liver, adipose tissue, muscle and pancreas and exerts actions in multiple targets including adipose, liver, pancreas and hypothalamus. The aim of this study was to examine the possible involvement of FGF21 in pancreatic and central control of glucose by measuring reflective changes in the release of insulin and glucagon.MethodsThirty adult male Wistar Albino rats were divided; Control, PD + aCSF, PD + FGF21 groups (n = 10). Effects of intracerebroventricular (icv) FGF21 administration to pancreatic denervated (PD) rats. Agouti-related protein (AgRP), Pro-opiomelanocortin (POMC) levels and blood glucose homeostasis were investigated.ResultsAdministration of FGF21 to 3rd ventricle increased food consumption but body weight didn't change significantly. AgRP level increased, pancreatic insulin levels increased, and glucagon level decreased.ConclusionCentral FGF21 administration is effective in regulating blood glucose homeostasis by increasing the amount and efficiency of insulin and changing glucose use.Öğe Effects of Cerebral Glucagon Administration on Blood Glucose Homeostasis in Rats(Wiley, 2023) Tanbek, Kevser; Yilmaz, Umit; Gul, Mehmet; Koc, Ahmet; Sandal, Suleyman[Abstract Not Available]Öğe The Effects of Different Burn Dressings on Length of Telomere and Expression of Telomerase in Children With Thermal Burns(Oxford Univ Press, 2019) Gurunluoglu, Kubilay; Demircan, Mehmet; Koc, Ahmet; Kocbiyik, Alper; Tasci, Aytac; Durmus, Kubra; Gurunluoglu, SemraBackground: Burns are a common traumatic injury triggered by local tissue damage and a systemic response. In this study, we evaluated the effects of different burn dressings on telomere kinetics in children with thermal burn injury. Methods: Sixty children with thermal burn were included in this prospective study. The burn area of the patients included 20 to 50% total body surface area. Three different dressings (hydrofiber with silver [HFAg], poylactic membrane [PLM], and silver sulfadiazine [SSD]) and control groups were created. Telomere length in nucleated blood cells and telomerase expression in the skin tissue were evaluated in control and burn groups. Results: In the whole burn groups, telomere length in blood cells increased. The length of telomeres increased the most in the SSD group. The PLM group is the treatment that increases the number of squamous cell counts in the basal layer and telomerase expression in the skin. In HFAg and SSD groups, the expression of telomerase in the skin is decreased. In the HFAg group, the basal layer in the skin was also reduced in squamous cells. Conclusion: In all burn groups, the telomere length of nucleated cells in the blood was higher than in the control group. SSD dressing along with autografting is the treatment method that maximizes telomere length in blood cells. The PLM has the most increased telomerase expression in the skin of burned patients. The PLM application increases the number of cells on both burned and normal skin.Öğe Effects of Glucagon on Central Nervous System in Regulating Glucose Homeostasis in Rats(Wiley, 2022) Tanbek, Kevser; Yilmaz, Umit; Gul, Semir; Koc, Ahmet; Gul, Mehmet; Sandal, Suleyman[Abstract Not Available]Öğe Effects of Severe Aerobic Exercise on Endoplasmic Reticulum Stress and Cellular Damage(Wiley, 2022) Korkmaz, Kubranur; Duzova, Halil; Durmus, Kubra; Koc, Ahmet; Taslidere, Asli Cetin[Abstract Not Available]Öğe Evaluation of genotoxic and mitotoxic effects of TAF-loaded chitosan nanoparticles in HepG2 cells(Taylor & Francis Ltd, 2024) Sezer, Selcen Korkmaz; Yuksel, Sengul; Koc, Ahmet; Ulu, Ahmet; Ates, BurhanTenofovir alafenamide (TAF) is a new drug from the nucleotide reverse transcriptase inhibitor group approved for the treatment of chronic Hepatitis B in 2016. With this study, we aimed to test whether possible cellular toxicity can be reduced by controlled drug release as a result of loading with chitosan nanoparticles (CHS). We investigated the genotoxic and mitotoxic effects of 45 mu M TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (Delta Psi m), and ROS levels. Additionally, we compared the samples by RNAseq analyses to reveal the transcriptional responses to each regimen. In terms of genotoxic tests, although MN and comet were found higher in all experimental treatment conditions, the encapsulation of CHS reduced the genotoxicity of TAF. MtDNA level was found to be lower in the TAF treatment, whereas it was higher in CHS and CHS-TAF treatments. The TAF-loaded CHS and TAF treatments had an impaired Delta Psi m value. Cellular ROS levels were higher in all treatment conditions. According to the analyses of gene expression patterns; CHS-only changed the expression of relatively few genes (187 genes), while TAF changed the expression of the 1974 genes and TAF-loaded CHS changed the expression of 734 genes. Considering the gene expression numbers, CHS encapsulation of TAF significantly reduced the number of genes that were differentially expressed by TAF-only. Overall, we observed that TAF has genotoxic and mitotoxic effects on HepG2 cells, and upon encapsulation with CHS, its genotoxic and mitotoxic effects were decreased.Öğe Evaluation of the Relationship Between Neurologic Manifestations and Genetic Mutations in Wilson's Disease with Next-Generation Sequencing(Mdpi, 2025) Akbulut, Sami; Is, Seyma; Koprulu, Tugba Kul; Varol, Fatma Ilknur; Kucukakcali, Zeynep; Colak, Cemil; Koc, AhmetBackground: Wilson's disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, leading to copper accumulation in the liver and brain. Given the clinical heterogeneity of the disease, this study aimed to characterize the mutational spectrum of ATP7B and explore genotype-phenotype correlations in Turkish patients. Methods: Whole-exome sequencing (WES) was performed in 17 Turkish patients clinically diagnosed with WD. Variants were annotated and evaluated using five in silico prediction tools (REVEL, CADD, PolyPhen, SIFT, MutationTaster). Copy number variation (CNV) analysis was conducted using the CLC Genomics Server (Version 22.0.2). Results: A total of 14 distinct ATP7B variants were identified, comprising 12 missense, 1 nonsense, and 1 frameshift mutation. Variant distribution showed some phenotype-specific patterns: four variants were found more frequently in hepatic cases and three in neurological cases, although no statistically significant or consistent correlation between genotype and clinical presentation could be established. The most frequent mutation was p.His1069Gln, present in both phenotypes. All missense variants were predicted to be pathogenic by at least three computational tools, with high concordance among platforms. No pathogenic CNVs were detected. Conclusions: This study expands the mutational landscape of ATP7B in Turkish patients with WD and supports the utility of WES combined with in silico tools for accurate variant classification. The results emphasize the genetic heterogeneity of WD and suggest possible associations between certain mutations and clinical phenotypes.Öğe Familial Mediterranean fever gene variations could trigger VPS16-associated early-onset dystonia and diabetes mellitus: clinical identification of a family with MEFV and VPS16 genetic variation association(Oxford Univ Press, 2024) Gemici, Yagmur Inalkac; Ekici, Cemal; Batum, Melike; Akbostanci, Cenk; Koc, Ahmet; Mavioglu, HaticeObjectives We describe the clinical pictures of an index case with dystonia and his family resulting from VPS16 and MEFV genetic variations based on previously published data and discuss the mechanisms that may have brought out the clinical findings. Methods A 17-year-old male had generalized dystonia that started at age 6 years, non-febrile abdominal pain attacks and was diagnosed with type 1 diabetes at age 14 years. Meanwhile, his 13-year-old sister had the same clinical presentation. His father was diabetic and his mother was asymptomatic. There was no consanguinity between the parents. Genetic variations were detected with whole exome sequencing. Results VPS16 c.1513C>T/p.Arg505* (likely pathogenic), MEFV c.2080A>G p.Met694val (pathogenic) and MEFV c.1772T>C p.Ile591Thr (unknown significance) heterozygous variants were detected in his siblings. The father had VPS16 c.1513C>T/p.Arg505* and MEFV c.2080A>G p Met694val variations and the mother had MEFV c.1772T>C p.Ile591Thr variations. Conclusions The occurrence of these diseases in siblings but their absence in the parents suggests the idea that the coexistence of two separate variations in the VPS16 and MEFV genes determines the phenotype. In addition, the increase in MEFV variation load in this family and the fact that DM occurs at an earlier age suggest that inflammation may cause an early diabetic clinical presentation.Öğe The importance of boron in biological systems(Elsevier Gmbh, 2018) Uluisik, Irem; Karakaya, Huseyin Caglar; Koc, AhmetBoron is an essential element for plants and probably essential for human and animal health. Boron has a broad range of physiological effects on biological systems at low concentrations, whereas it is toxic to at high concentrations. Eventhough there are many studies on boron's biological effects and toxicity, more information is needed to understand the mechanisms of its action. The aim of the current work is to review boron's function, transport and toxicity in different biological systems.Öğe The importance of boron in biological systems (vol 45, pg 156, 2018)(Elsevier Gmbh, 2019) Uluisik, Irem; Karakaya, Huseyin Caglar; Koc, Ahmet[Abstract Not Available]Öğe Inflammatory parameters in gingival crevicular fluid and saliva of patients with celiac disease: a comparative analysis(Springer Heidelberg, 2025) Sabanci, Arife; Kirmizigul, Omer Alperen; Ozgen, Nazmi; Sabanci, Halil Ibrahim; Koc, Ahmet; Disli, Faruk; Yildiz, SedatObjective Celiac disease (CD) is an immune-mediated chronic enteropathy that causes chronic inflammation and has been found to cause oral health problems. The aim of this study was to compare the levels of the inflammatory markers calcium (Ca), caspase-1 and tumor necrosis factor-alpha (TNF-alpha) in the gingival crevicular fluid (GCF) and saliva of patients with and without celiac disease. Methods A total of 60 participants were divided into two groups: patients with celiac disease on a gluten diet (C) (n = 30) and systemically healthy controls (H) (n = 30). Full-mouth periodontal measurements, including the gingival index (GI), plaque index (PI), bleeding on probing (BOP), and probing depth (PD), were recorded for all participants. Saliva and GCF samples were collected for analysis of the levels of TNF-alpha, Ca, and caspase-1 via enzyme-linked immunosorbent assay (ELISA). Results Salivary and GCF Ca, caspase-1, and TNF-alpha levels were not different between the two groups (p > 0.05). Conclusions Oral inflammatory profiles of celiac disease patients on a gluten-free diet show similarities with systemically healthy individuals.Öğe Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis(Wiley, 2024) Yilmaz, Umit; Tanbek, Kevser; Gul, Semir; Koc, Ahmet; Gul, Mehmet; Sandal, SuleymanHere, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin-1, LC3, p62 and cleaved caspase-3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin-1, LC3 and p62 and inhibiting the apoptotic caspase-3 protein while its beneficial effects were apparent in neurological tests from the 4th day.Öğe Investigation of genetic causes in non-obstructive azoospermic patients(Mre Press, 2025) Dural, Bulut; Gecit, Ilhan; Aykanli, Emre; Ekici, Cemal; Oguz, Fatih; Koc, AhmetBackground: Male factor infertility is a health problem that affects millions of couples around the world. Male factor infertility is responsible for approximately more than half of all cases of infertility. About 15% of men and 10% of women with infertility may have genetic abnormalities, including chromosomal abnormalities and single gene mutations. In this study, results of genetic analys is of the infertile male patients who underwent testicular sperm extraction (TESE) with the diagnosis of nonobstructive azoospermia were evaluated in order to reveal genetic defects that impair or prevent spermatogenesis in male infertility. Methods: We compared the results of peripheral blood chromosome analysis, molecular karyotyping, male infertility genetic panel, and also testosterone, prolactin, follicular stimulating hormone and luteinizing hormone levels in non-obstructive azoospermic infertile patients aged 26-44 years, and investigated the relationship between these parameters and genetic mutations. Results: As a result of this research, among 26 patients, INSL3 (insulin-like peptide 3) gene mutation, which is considered pathogenic according to the criteria published by the American College of Medical Genetics and Genomics (ACMG) was detected in 1, FSHR (follicle stimulating hormone receptor) gene polymorphism in 17, CFTR (cystic fibrosis transmembrane conductance regulator) mutations in 5, CATSPER1 (cation channel sperm associated 1) and TEX101 (testis expressed 101) in 1, LHCGR (luteinizing hormone/choriogonadotropin receptor) in 1, ZMYND15 (zinc finger myndtype containing 15) in 1, DNAH5 (dynein axonemal heavy chain 5) in 2, and DNAH11 (dynein axonemal heavy chain 11) changes in 1 patient. In the chromosome analysis, 47XXY Klinefelter syndrome was observed in 6 patients. Conclusions: The results have shown that non-obstructivea zoospermic patients with complaints of infertility may have other genetic abnormalities leading to infertility, despite the results of chromosomal analysis of the peripheral blood samples were within normal reference limits. Investigating these underlying genetic disorders helped us find the cause of infertility in ourpatient population.Öğe Investigation of the cardiotoxic effects of parenteral nutrition in rabbits(W B Saunders Co-Elsevier Inc, 2020) Gurunluoglu, Kubilay; Gul, Mehmet; Kocbiyik, Alper; Koc, Ahmet; Uremis, Nuray; Gurunluoglu, Semra; Bag, Harika GozukaraIntroduction: Parenteral nutrition (PN) is used for the intravenous delivery of nutrients to patients who cannot take food orally. However, it is not clear whether PN also negatively impacts cardiac tissue. The present empirical study investigated the cardiac effects of PN in rabbits. Methods: The effects of PN were examined in three groups of rabbits: animals in the PN + fasting group (n = 14) had been fully fasted before receiving a full PN dose via an intravenous central catheter; the PN + oral feeding group (n = 14) received half of the daily calorie requirement as a half dose of PN via an intravenous central catheter; the third group consisted of controls (n = 14) with full enteral feeding and full enteral fluid intake with no PN and no central venous catheter. Al the end of the 10-day study period, the rabbits were subjected to echocardiographic examination and euthanized. Blood and tissue samples were obtained from all groups. DNA was isolated from nucleated blood cells. Tissue samples were examined by both light and electron microscopy, relative telomere length was determined from DNA, and blood samples were analyzed biochemically. Results: At the end of the study, there were no statistically significant differences in weight change between the three groups. Echocardiography revealed minimally impaired diastolic function in the PN + fasting group compared to the other groups. Biochemical and histopathological analyses, relative telomere length determination, and electron micrographs showed significant cardiac damage in the PN + fasting group but not in the PN + oral feeding group or the control group. The blood biochemical analyses showed hyperglycemia and a low insulin level in the PN + fasting group but not in the other two groups. Conclusions: A combination of PN and fasting may damage the cardiac muscle cells of rabbits via a mechanism involving hyperglycemia and oxidative stress. Additional enteral feeding may protect against the destructive effects of PN on cardiac tissue. (C) 2019 Elsevier Inc. All rights reserved.Öğe Investigation of the Neuroprotective Effect of N-(p-amylcinnamoyl) Anthranilic Acid on Hippocampal Endoplasmic Reticulum Stress in WAG/Rij Rats with Absence Epilepsy(Wiley, 2022) Kaya, Gul Busra; Duzova, Halil; Kaya, Mehmet; Dundar, Muhammed; Koc, Ahmet[Abstract Not Available]











