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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 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 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 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]Öğe Melatonin Attenuates Cerebral Ischemia/Reperfusion Injury Through Inducing Autophagy(Karger, 2023) Yilmaz, Umit; Tanbek, Kevser; Gul, Semir; Gul, Mehmet; Koc, Ahmet; Sandal, SuleymanIntroduction: The aim of this study was to investigate how melatonin administration for 3 days or 7 days following cerebral ischemia injury (CI/R) would affect autophagy, and therefore, survival in neurons of the penumbra region. Moreover, it was also aimed to determine how this melatonin treatment would affect the neurological deficit score and rotarod and adhesive removal test durations.Methods: Focal CI (90 min) was achieved in a total of 105 rats utilizing a middle cerebral artery occlusion model. After the start of reperfusion, the groups were treated with melatonin (10 mg/kg/day) for 3-days or 7-days. On all groups, neurological deficit scoring, rotarod and adhesive removal test were executed during reperfusion. Infarct areas were determined by TTC (2,3,5-triphenyltetrazolium chloride) staining at the end of the 3rd and 7th days of reperfusion. Beclin-1, LC3, p62 and caspase-3 protein levels were assessed using Western blot and immunofluorescence methods in the brain tissues. Moreover, penumbra areas were evaluated by transmission electron microscopy (TEM).Results: Following CI, it was observed that melatonin treatment improved the rotarod and adhesive removal test durations from day 5 and reduced the infarct area after CI. It also induced autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. According to TEM findings, melatonin treatment partially reduced the damage in neurons after CI.Conclusion: Melatonin treatment following CI reduced the infarct area and induced the autophagic proteins Beclin-1, LC3 and p62 via inhibiting the apoptotic caspase-3 protein. The functional reflection of melatonin treatment on neurological tests scores was became significant from the 5th day onward.Öğe N-alkylbenzimidazole silver(I) complexes: Synthesis, biological evaluation and molecular docking study(Pergamon-Elsevier Science Ltd, 2024) Ari, Erkan; Sahin, Neslihan; Ustun, Elvan; Dundar, Muhammed; Karci, Huseyin; Ozdemir, Lknur; Koc, AhmetA series of N-alkylbenzimidazole silver(I) complexes were synthesized and fully characterized by FT-IR, Mass, 1H, 13C{1H} NMR spectroscopy, and elemental analysis. Synthesized N-alkylbenzimidazole silver(I) complexes were investigated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. All the complexes (2a-f) showed higher antimicrobial activity against bacteria than fungi strains. In particular, complexes 2b and 2e showed comparable activity to Ampicillin against Escherichia coli. Also, all complexes showed better activity than Ampicillin against Pseudomonas aeruginosa. The complex 2e showed remarkable activity against Candida albicans (12.5 mu g/mL) and Candida glabrata (25 mu g/mL). The molecules that were first optimized by DFT-based calculation methods were also analyzed by molecular docking methods against DNA gyrase of E. Coli, CYP51 from Candida glabrata, and Penicillin Binding Protein-3.Öğe Novel benzimidazolium salts and their silver(I)-N-heterocyclic carbene complexes: synthesis, characterization and their biological properties(Taylor & Francis Ltd, 2023) Belhi, Zeyneb; Karci, Huseyin; Dundar, Muhammet; Gurbuz, Nevin; Ozdemir, Ilknur; Koc, Ahmet; Cheriti, AbdelkrimThis study was conducted to synthesize and characterize 1,3-dialkyl-5,6-dimethyl-benzimidazolium salts and their silver complexes. Four novel silver(I)-N-heterocyclic carbene complexes were synthesized and characterized by mass analyses, FT-IR and NMR spectroscopy. The biological capacity of the synthesized compounds was evaluated in vitro for their antimicrobial and antitumor activities. The minimum inhibitory concentration (MIC) of the 1,3-dialkyl-5,6-dimethyl-benzimidazolium salts and their complexes was determined for E. coli, P. aeruginosa, S. aureus, C. glabrata and C. albicans in vitro through BMD (Broth Microdilution). The results indicated that silver(I)-NHC complexes exhibit antimicrobial activity. In particular, complex 3c presented a significant broad-spectrum antimicrobial activity. The anticancer properties of the synthesized compounds were evaluated against MCF-7, HCT116, SH-SY5Y and BEAS-2B cell lines. Anticancer activity measurements were carried out according to the Alamar Blue assay. Efficacy was established by comparison of the salts and silver compounds with cisplatin.Öğe Preparation, Controlled Drug Release, and Cell Viability Evaluation of Tenofovir Alafenamide-Loaded Chitosan Nanoparticles(Wiley-V C H Verlag Gmbh, 2024) Ulu, Ahmet; Sezer, Selcen Korkmaz; Yuksel, Sengul; Koc, Ahmet; Ates, BurhanTenofovir alafenamide (TAF) is used as a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor for the treatment of chronic HBV infection. However, the use of TAF suffers from its poor solubility and low bioavailability. Therefore, this study prepared and characterized chitosan nanoparticles (CHS NPs) loaded with TAF. Morphological findings demonstrated that CHS NPs are roughly spherical and homogeneous in shape. Besides, TAF-loaded CHS NPs displayed the hydrodynamic diameter, zeta potential, and PDI of approximately 340 nm, 48.9 mV, and 0.65, respectively. The encapsulation efficiency is at about 50%, and TAF is released about 93% at the end of 80 hours at pH 7.4. In addition, human hepatocellular carcinoma cells (HepG2) are used for cell viability studies and it is observed that TAF-loaded CHS NPs has 1.24 times less viable cells as compared to the control. Collectively, TAF-loaded CHS NPs could be used as an efficient formulation for the treatment of chronic HBV infection.Öğe A Rare Mosaic Karyotype of 45,X/46,X,psu idic(Y)(p11.32)/46, XY with SHOX Haploinsufficiency, External Male Genitalia, and Short Stature(Karger, 2019) Ekici, Cemal; Esener, Zeynep; Korkmaz, Selcen; Salturk, Nihal; Yuksel, Sengul; Koc, AhmetIn this case study, we describe a 3-year-old boy who was referred to the Inonu University Hospital with short stature complaint. His height was 86 cm (-2.96 SDS), weight was 12 kg (-2.43 SDS), and head circumference was 46.5 cm (-2.34 SDS). Chromosomal analyses were performed on cultured peripheral blood lymphocytes of the patient and his parents and showed the patient's karyotype mos 45, X[20]/46, X, idic(Y)(p11.32)[29]/46, XY[1]. The karyotypes of the parents were normal. Subsequently, specific FISH probes were hybridized to the related regions of the sex-determining region Y (SRY), centromere X/Y (CEP X/Y), and short stature homeobox (SHOX) genes. Simultaneous SNP array-CGH was conducted. As to our knowledge, we present the first patient with mosaic isodicentric Y chromosome with 3 different cell lines and normal male external genitalia. Our results suggest that it would be beneficial to study cytogenetic and molecular cytogenetic methods together for better diagnostic accuracy and treatment. (C) 2018 S. Karger AG, Basel
