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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 Citation - WoS: 3Citation - Scopus: 3Characterization of Mesenchymal Stem Cells in Mucolipidosis Type Ii (i-Cell Disease)(Tubitak Scientific & Technological Research Council Turkey, 2019) Köse, Sevil; Kaya, Fatima Aerts; Kuşkonmaz, Bülent Barış; Çetinkaya, Duygu Uçkan; Aerts Kaya, Fatima; Uckan Cetinkaya, DuyguMucolipidosis type II (ML-II, I-cell disease) is a fatal inherited lysosomal storage disease caused by a deficiency of theenzyme N-acetylglucosamine-1-phosphotransferase. A characteristic skeletal phenotype is one of the many clinical manifestationsof ML-II. Since the mechanisms underlying these skeletal defects in ML-II are not completely understood, we hypothesized that adefect in osteogenic differentiation of ML-II bone marrow mesenchymal stem cells (BM-MSCs) might be responsible for this skeletalphenotype. Here, we assessed and characterized the cellular phenotype of BM-MSCs from a ML-II patient before (BBMT) and afterBM transplantation (ABMT), and we compared the results with BM-MSCs from a carrier and a healthy donor. Morphologically, wedid not observe differences in ML-II BBMT and ABMT or carrier MSCs in terms of size or granularity. Osteogenic differentiation wasnot markedly affected by disease or carrier status. Adipogenic differentiation was increased in BBMT ML-II MSCs, but chondrogenicdifferentiation was decreased in both BBMT and ABMT ML-II MSCs. Immunophenotypically no significant differences were observedbetween the samples. Interestingly, the proliferative capacity of BBMT and ABMT ML-II MSCs was increased in comparison to MSCsfrom age-matched healthy donors. These data suggest that MSCs are not likely to cause the skeletal phenotype observed in ML-II, butthey may contribute to the pathogenesis of ML-II as a result of lysosomal storage-induced pathology.Article Citation - WoS: 9Citation - Scopus: 10Impact of Hospital-Acquired Acute Kidney Injury on Covid-19 Outcomes in Patients With and Without Chronic Kidney Disease: a Multicenter Retrospective Cohort Study(Tubitak Scientific & Technological Research Council Turkey, 2021) Ozturk, Savas; Turgutalp, Kenan; Arıcı, Mustafa; Çetinkaya, Hakkı; Altıparmak, Mehmet Rıza; Aydın, Zeki; Ateş, Kenan; Dolarslan, Mursıde Esra; Seyahi, Nurhan; Yıldız, Alaattın; Bora, FeyzaBackground/aim: Hospital-acquired acute kidney injury (HA-AKI) may commonly develop in Covid-19 patients and is expected to have higher mortality. There is little comparative data investigating the effect of HA-AKI on mortality of chronic kidney disease (CKD) patients and a control group of general population suffering from Covid-19. Materials and methods: HA-AKI development was assessed in a group of stage 3–5 CKD patients and control group without CKD among adult patients hospitalized for Covid-19. The role of AKI development on the outcome (in-hospital mortality and admission to the intensive care unit [ICU]) of patients with and without CKD was compared. Results: Among 621 hospitalized patients (age 60 [IQR: 47–73]), women: 44.1%), AKI developed in 32.5% of the patients, as stage 1 in 84.2%, stage 2 in 8.4%, and stage 3 in 7.4%. AKI developed in 48.0 % of CKD patients, whereas it developed in 17.6% of patients without CKD. CKD patients with HA-AKI had the highest mortality rate of 41.1% compared to 14.3% of patients with HA-AKI but no CKD (p < 0.001). However, patients with AKI+non-CKD had similar rates of ICU admission, mechanical ventilation, and death rate to patients with CKD without AKI. Adjusted mortality risks of the AKI+non-CKD group (HR: 9.0, 95% CI: 1.9–44.2) and AKI+CKD group (HR: 7.9, 95% CI: 1.9–33.3) were significantly higher than that of the non-AKI+non-CKD group. Conclusion: AKI frequently develops in hospitalized patients due to Covid-19 and is associated with high mortality. HA-AKI has worse outcomes whether it develops in patients with or without CKD, but the worst outcome was seen in AKI+CKD patients.Key words: Acute kidney injury, chronic kidney disease, Covid-19, hospitalization, mortalityArticle Citation - WoS: 6Citation - Scopus: 6The Role of Anakinra in the Modulation of Intestinal Cell Apoptosis and Inflammatory Response During Ischemia/Reperfusion(Tubitak Scientific & Technological Research Council Turkey, 2021) Kandemir, Muhammed; Bektur Aykanat, Nuriye Ezgi; Yaşar, Necdet Fatih; Özkurt, Mete; Özyurt, Rumeysa; Aykanat, Nuriye Ezgi Bektur; Erkasap, Nilüfer; Bektur Aykanat, Nuriye Ezgi; Bektur, Ezgi; Basic Sciences; Basic SciencesBackground/aim: Even though interleukin-1 receptor antagonist, IL-1Ra, is used in certain inflammatory diseases, its effect on ischemia-reperfusion injury is a current research topic. We aimed to investigate the protective effects of anakinra, an IL-1Ra, on the I/R induced intestinal injury. Materials and methods: The rat model of intestinal ischemia-reperfusion was induced. Rats were randomized into 4 groups: (group 1) control group, (group 2) I/R group, (group 3 and 4) treatment groups (50 mg/kg and 100 mg/kg, respectively). Gene expressions of caspase-3, TNF-α, IL-1α, IL-6, and apoptotic cells in tissue samples were evaluated by PCR and TUNEL methods, respectively. Plasma levels of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were studied by the ELISA method and tissue samples were examined histopathologically as well. Results: Anakinra inhibited the expression of IL-1α, IL-6, and TNF-α and decreased the SOD, CAT, and MDA caused by ischemiareperfusion injury in both treatment groups. Caspase-3 expression and TUNEL-positive cell number in treatment groups were also less. Histopathologically, anakinra better preserved the villous structure of the small intestine at a dose of 100 mg/kg than 50 mg/kg.Conclusion: Anakinra decreased the intestinal damage caused by ischemia-reperfusion and a dose of 100 mg/kg was found to be histopathologically more effective.Key words: Ischemia reperfusion injury, interleukin-1 receptor antagonist, anakinraArticle Citation - WoS: 16Citation - Scopus: 19The Triglyceride-Glucose Index Predicts Peripheral Artery Disease Complexity(Tubitak Scientific & Technological Research Council Turkey, 2020) Karaduman, Bilge Duran; Ayhan, Hüseyin; Keles, Telat; Bozkurt, Engin; Duran Karaduman, BilgeBackground/aim: High levels of triglyceride (TG) and fasting blood glucose (FBG) values increase atherosclerosis risk. This study\revaluates the relationship between peripheral artery disease (PAD) severity and complexity, as assessed by TransAtlantic InterSociety\rConsensus-II (TASC-II) classification and the triglyceride-glucose (TyG) index.\rMaterials and methods: A total of 71 consecutive patients with PAD (males 93%, mean age 63.3 ± 9.7), who underwent percutaneous\rperipheral intervention were included retrospectively. The patients were divided into two groups according to the angiographically\rdetected lesions. Those with TASC A-B lesions were included in Group 1, and those with TASC C-D lesions were included in Group 2.\rTyG index was calculated as formula: ln[fasting TG (mg/dL) × fasting plasma glucose (mg/dL)/2].\rResults: There were 40 patients in Group 1 (90.3% men, with a mean age of 63.6 ± 9.3 years) and 31 patients in Group 2 (96.8% men,\rwith a mean age of 62.0 ± 8.6 years). In the majority of patients in both groups, the target vessels are iliac arteries and femoral arteries.\rIn Group 2, platelet count and TyG index were significantly high, according to Group 1. The TyG index was significantly correlated with\rTASC-II, Rutherford category, HbA1c, and HDL-C.\rConclusion: In this present study, we showed that the TyG index was an independent predictor of peripheral artery disease complexity,\raccording to TASC-II classification, for the first time in the literature.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.
