5 results
Search Results
Now showing 1 - 5 of 5
Article Citation - WoS: 3Citation - Scopus: 5Investigation of the Effect of Hyperthyroidism on Endoplasmic Reticulum Stress and Transient Receptor Potential Canonical 1 Channel in the Kidney(Tubitak Scientific & Technological Research Council Turkey, 2021) Aykanat, Nuriye Ezgi Bektur; Şahin, Erhan; Kaçar, Sedat; Bağcı, Rıdvan; Karakaya, Şerife; Dönmez, Dilek Burukoğlu; Şahintürk, Varol; Bektur Aykanat, Nuriye Ezgi; Burukoğlu Dönmez, Dilek; Bektur, EzgiBackground/aim: Hyperthyroidism is associated with results in increased glomerular filtration rate as well as increased renin-angiotensin-aldosterone activation. The disturbance of Ca2+ homeostasis in the endoplasmic reticulum (ER) is associated with many diseases, including diabetic nephropathy and hyperthyroidism. Transient receptor potential canonical 1 (TRPC1) channel is the first cloned TRPC family protein. Although it is expressed in many places in the kidney, its function is uncertain. TRPC1 is involved in regulating Ca2+ homeostasis, and its upregulation increases ER Ca2+ level, activates the unfolded protein response, which leads to cellular damage in the kidney. This study investigated the role of TRPC1 in the kidneys of hyperthyroid rats in terms of ER stress markers that are glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), (protein kinase R (PKR)-like endoplasmic reticulum kinase) (PERK), Inositol-requiring enzyme 1 (IRE1). Materials and methods: Twenty male rats were assigned into control and hyperthyroid groups (n = 10). Hyperthyroidism was induced by adding 12 mg/L thyroxine into the drinking water of rats for 4 weeks. The serum-free T3 and T4 (fT3, fT4), TSH, blood urea nitrogen (BUN), and creatinine levels were measured. The histochemical analysis of kidney sections for morphological changes and also immunohistochemical and western blot analysis of kidney sections were performed for GRP78, ATF6, PERK, IRE1, TRPC1 antibodies. Results: TSH, BUN, and creatinine levels decreased while fT3 and fT4 levels increased in the hyperthyroid rat. The morphologic analysis resulted in the capillary basal membrane thickening in glomeruli and also western blot, and immunohistochemical results showed an increase in TRPC1, GRP78, and ATF6 in the hyperthyroid rat (p < 0.05). Conclusion: In conclusion, in our study, we showed for the first time that the relationship between ER stress and TRPC1, and their increased expression caused renal damage in hyperthyroid rats.Key words: Hyperthyroidism, endoplasmic reticulum (ER) stress, transient receptor potential canonical 1 (TRPC1), kidney, ratArticle Neuron Modeling: Estimating the Parameters of a Neuron Model From Neural Spiking Data(Tubitak Scientific & Technological Research Council Turkey, 2018) Doruk, Resat Ozgur; Doruk, OzgurWe present a modeling study aiming at the estimation of the parameters of a single neuron model from neural spiking data. The model receives a stimulus as input and provides the firing rate of the neuron as output. The neural spiking data will be obtained from point process simulation. The resultant data will be used in parameter estimation based on the inhomogeneous Poisson maximum likelihood method. The model will be stimulated by various forms of stimuli, which are modeled by a Fourier series (FS), exponential functions, and radial basis functions (RBFs). Tabulated results presenting cases with different sample sizes (# of repeated trials), stimulus component sizes (FS and RBF), amplitudes, and frequency ranges (FS) will be presented to validate the approach and provide a means of comparison. The results showed that regardless of the stimulus type, the most effective parameter on the estimation performance appears to be the sample size. In addition, the lowest variance of the estimates is obtained when a Fourier series stimulus is applied in the estimation.Article Fitting a Recurrent Dynamical Neural Network To Neural Spiking Data: Tackling the Sigmoidal Gain Function Issues(Tubitak Scientific & Technological Research Council Turkey, 2019) Doruk, Reşat ÖzgürThis is a continuation of a recent study (Doruk RO, Zhang K. Fitting of dynamic recurrent neural networkmodels to sensory stimulus-response data. J Biol Phys 2018; 44: 449-469), where a continuous time dynamical recurrentneural network is fitted to neural spiking data. In this research, we address the issues arising from the inclusion ofsigmoidal gain function parameters to the estimation algorithm. The neural spiking data will be obtained from the samemodel as that of Doruk and Zhang, but we propose a different model for identification. This will also be a continuoustime recurrent neural network, but with generic sigmoidal gains. The simulation framework and estimation algorithmsare kept similar to that of Doruk and Zhang so that we can have a solid base to compare the results. We evaluatethe estimation performance in two different ways. First, we compare the firing rate responses of the original and theestimated model. We find that responses of both models to the same stimuli are similar. Secondly, we evaluate variationsof the standard deviations of the estimates against a number of samples and stimulus parameters. They show a similarpattern to that of Doruk and Zhang. We thus conclude that our model serves as a reasonable alternative provided thatfiring rate is the response of interest (to any stimulus).Article Citation - WoS: 1Citation - Scopus: 2Cannabinoid Receptor Ligands Modulate Fibrosis and Inflammation in Idiopathic Pulmonary Fibrosis: a Preliminary Study(Tubitak Scientific & Technological Research Council Turkey, 2024) Kose, Sevil; Onen, Selin; Gizer, Merve; Boduroglu, Esin; Gonullu, Ugur; Korkusuz, PetekBackground/aim: No specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF) exists. Therefore, new antiinflammatory therapeutic strategies are needed. Cannabinoids (CBs), known for their inflammation-modulating and antifibrotic effects, may be potential medication candidates for treating IPF. We aim to evaluate the inflammation-modulating and antifibrotic effects of CB receptor (CBR) agonists and antagonists in lipopolysaccharide-stimulated normal human lung fibroblast, epithelial cells, IPF fibroblast cells, and monocytes. Materials and methods: We detected CBRs in normal human lung fibroblasts (LL24) and IPF fibroblast cells (LL29), epithelial cells (A549) and monocytes (THP-1) by flow cytometry. We determined TGF-(31, IL-8, and TNF-alpha inflammatory cytokines in the LL24, LL29, A549, and THP-1 cell culture supernatants on days 1 and 5 by ELISA. We evaluated the cell viability in LL24, LL29, and A549 cells on days 1, 3, and 5 spectrophotometrically and detected collagen Type I (ColI) production in the LL24 and LL29 cell culture supernatants on days 1, 3, and 5 by ELISA. Results: LL24, LL29, A549, and THP-1 cells exhibited CB1 (CB1R) and CB2 (CB2R) receptors. CB1R and CB2R agonists WIN55,2122 and JWH015 inhibited fibroblastic and epithelial cell proliferation on day 5. TGF-(31 and TNF-alpha release increased, while IL-8 release decreased in LL24, LL29, A549, and THP-1 cells in response to the administration of WIN55,212-2 and JWH015 at a 10-2 mM concentration. CB1R and CB2R antagonists AM251 and AM630 did not block agonistic responses, suggesting a nonclassical CBRmediated pathway. CB2R agonist JWH015 decreased ColI expression in IPF lung fibroblasts LL29 on day 3. Conclusion: These results suggest that CB signaling regulates the progression of pulmonary inflammation and fibrosis via CBR activation. This may offer a potential pharmacological tool for developing antifibrosis therapies.Article Citation - WoS: 13Citation - Scopus: 13Association between monocyte to high-density lipoprotein cholesterol ratio and bicuspid\raortic valve degeneration(Tubitak Scientific & Technological Research Council Turkey, 2020) Karaduman, Bilge Duran; Ayhan, Hüseyin; Keles, Telat; Bozkurt, Engin; Duran Karaduman, BilgeBackground/aim: From a pathophysiological point of view, inflammation is thought to be more dominant in bicuspid aortic valve\r(BAV) stenosis than tricuspid aortic valve (TAV) stenosis. Our study aimed to determine the association between monocyte to highdensity lipoprotein cholesterol (HDL-C) ratio (MHR), a new inflammatory marker, and the speed of progression of stenosis and\rpathophysiology of BAV stenosis.\rMaterials and methods: A total of 210 severe aortic stenosis patients (70 consecutive BAV patients, 140 matched TAV patients) were\rretrospectively enrolled in the study. Clinical and echocardiographic data and laboratory results related to our research were collected\rretrospectively from the patients’ records. MHR was measured as the ratio of the absolute monocyte count to the HDL-C value.\rResults: Seventy BAV (mean age: 72.0 ± 9.1 years, 42.9% female) and 140 TAV patients (mean age: 77.9 ± 8.3 years, 51.4% female)\rwith severe aortic stenosis were enrolled in this study. There was no difference between the two groups in terms of another baseline\rdemographic or clinic findings except age (P < 0.001). Monocyte count, hemoglobin level, mean platelet volume was significantly\rhigher, and HDL-C level was significantly lower in the BAV group, while other lipid and CBC parameters were found to be similar. In\rthe multivariate analysis, MHR (P = 0.005, 95% CI: 0.90–0.98) and, as expected, age (P = 0.001, 95% CI: 1.02–1.11) were found to be\rsignificant as the independent predictor of BAV, after adjusting for other risk factors.\rConclusion: Our study showed a significant correlation between increased MHR and BAV. MHR was determined as a significant\rindependent predictor for the speed of progression and diagnosis of severe BAV stenosis in multivariate analysis.
