Araştırma Çıktıları
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Item Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection(MDPI, 2020-01-01) Palmeira, Andreia; Sousa, Emilia; Koseler, Aylin; Sabirli, Ramazan; Goren, Tarik; Turkcuer, Ibrahim; Kurt, Ozgur; Pinto, Madalena M.; Helena Vasconcelos, M.SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (-) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (-) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (-) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.Item Annexin A1 as a potential prognostic biomarker for COVID-19 disease: Case-control study(WILEY-HINDAWI, 2020-01-01) Canacik, Omer; Sabirli, Ramazan; Altintas, Emel; Karsli, Emre; Karis, Denizhan; Kaymaz, Buse; Sabirli, Gizem Tukenmez; Kurt, Ozgur; Koseler, AylinBackground Annexin A1 (AnxA1) is an important endogenous glucocoticoid protein that contributes to the suppression of inflammation by limiting the production of neutrophil and pro-inflammatory cytokines. This study aims to determine the clinical predictivity value of blood AnxA1 levels in patients with mild and severe-critical pneumonia induced by COVID-19. Methods This study employed a prospective, case-control study design and was conducted at Ankara Training and Research hospital between 10 February 2021 and 15 March 2021. A total of 74 patients (42 of whom had moderate and 32 of whom had severe/critical cases of COVID-19 disease according to World Health Organization guidelines) and 50 nonsymptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, AnxA1 levels were evaluated using the enzyme-linked immunosorbent assay method. Results The serum AnxA1 levels were measured as 25.5 (18.6-38.6) ng/ml in the control group, 21.2 (14.7-32) ng/ml in the moderate disease group, and 14.8 (9.7-26.8) ng/ml in the severe/critical disease group. Serum AnxA1 levels were significantly lower in the severe/critical disease group compared with the control and moderate disease groups (P = .01 and P = .0001, respectively). Using receiver operating characteristic analysis, a larger area under the curve (AUC) for the serum AnxA1 levels of the control group (AUC = 0.715, 95\% CI = 0.626-0.803Item Gaiectin-3 as a Potential Prognostic Biomarker for COVID-19 Disease: A Case-Control Study(CUREUS INC, 2022-01-01) Karsli, Emre; Metin, Damla Anabarli; Canacik, Omer; Sabirli, Ramazan; Kaymaz, Buse; Kurt, Ozgur; Koseler, AylinBackground Recent studies have investigated the importance of Galetin-3 in inflammation, fibrosis, cell proliferation, cardiac disease, diabetes, and tumor formation. Aims This study aims to investigate the role of the Galectin-3 level in the diagnosis of COVID-19 pneumonia and the value of the Galectin-3 level in predicting the clinical course of the patient. Methods This study employed a prospective, case-control study design and was conducted at Bakircay University Cigli Training and Research Hospital. A total of 100 patients (40 had moderate and 60 had severe/critical COVID-19 disease according to World Health Organisation guidelines) and 50 non-symptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, Galectin-3 levels were evaluated using the enzyme-linked immunosorbent assay (ELISA) method. Results The serum Galectin-3 level was measured as 13.57 (10.9-16.4) ng/mL in the control group, 13.52 (10.69-16.6) ng/mL in the moderate disease group, and 11.65 (6.09-14.33) ng/mL in the severe/critical disease group. Serum Galectin-3 levels were significantly lower in the severe/critical disease group compared to the control and moderate disease groups (p=0.001 and p=0.019, respectively). Using ROC analysis, a larger area under the curve (AUC) for the serum Galectin-3 levels of the control group (AUC-0.622, 95\% CI =0.529-0.714Item Soluble P-selectin as a potential diagnostic and prognostic biomarker for COVID-19 disease: A case-control study(PERGAMON-ELSEVIER SCIENCE LTD, 2021-01-01) Karsli, Emre; Sabirli, Ramazan; Altintas, Emel; Canacik, Omer; Sabirli, Gizem Tukenmez; Kaymaz, Buse; Kurt, Ozgur; Koseler, AylinIntroduction: To our knowledge, the diagnostic value of the sP-Selectin level in the diagnosis of COVID-19 disease has not yet been investigated. In this study, we aimed to assess this by evaluating the relationship between sPSelectin level and the clinical severity of COVID-19 infections. Methods: A total of 80 patients (50 with mild to moderate and 30 with severe COVID-19 pneumonia), and 60 nonsymptomatic healthy volunteers participated in the study. Following serum isolation, sP-Selectin levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: The serum sP-Selectin level was 1.7 ng/ml in the control group (1-3.78)Item Predictive Value of Endoplasmic Reticulum Stress Markers in Low Ejection Fractional Heart Failure(INT INST ANTICANCER RESEARCH, 2019-01-01) Sabirli, Ramazan; Koseler, Aylin; Mansur, Nesteren; Zeytunluoglu, Ali; Sabirli, Gizem Tukenmez; Turkcuer, Ibrahim; Kilic, Ismail DoguBackground/Aim: Endoplasmic reticulum (ER) stress plays a critical role in the development of cardiac hypertrophy and heart failure. Heart failure is a crucial health problem that affects 23 million people worldwide, causes approximately 2.4 million people to be hospitalized every year in the USA, and leads to the death of more than 300,000 people. In this study, we aimed to investigate the clinical significance of ER stress markers and the predictive value of acute decompensated heart failure in patients with low ejection fraction heart failure (ADHF). Patients and Methods: This is a prospective case control study. The data included laboratory parameters pertaining to patients with ADHF in the emergency service and lipid parameters obtained during their admission to the hospital. In addition, the same parameters obtained from the control group patients with chronic heart failure (CHF) during their routine polyclinic control were recorded in the data set. Admission time to the hospital and length of hospital stay were included in the data. The levels of glucose regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) in peripheral blood serum obtained from the patients and the control group were measured using the ELISA method. Results: Serum GRP78 concentration was lower in the HF group (p=0.003) compared to the control. The median value of serum PERK concentration in the HF group was higher than that of the control group (573 pg/ml, IQR=477.5-650 vs. 495.5 pg/ml, IQR=294-648, respectively) (p=0.001). However, there were no statistically significant differences in GRP78 and PERK serum concentrations between ADHF and CHF subgroups. Receiver operating characteristic (ROC) curve analysis showed greater area under the curve (AUC) for the serum GRP78 levels of the healthy individuals (AUC=0.748, 95\% CI=0.681-0.814, p=0.0003). The serum GRP78 level was found to be 80\% sensitive and 70\% specific at 147.5 pg/ml (p=0.0003) for distinguishing healthy individuals from HF patients. In the ADHF subgroup, there was a moderate correlation between hospitalization time and serum CHOP concentrations (Spearman rho=0.586 and p=0.001). Conclusion: High GRP78 serum concentration may protect the patient from ER stress. In addition, the serum PERK level is high in patients with HF, whereas it is insufficient in predicting acute decompensation. CHOP may be useful in predicting the length of hospital stay in patients with ADHF.Item Association Between S100b Levels and COVID-19 Pneumonia: A Case Control Study(INT INST ANTICANCER RESEARCH, 2021-01-01) Mete, Ergun; Sabirli, Ramazan; Goren, Tarik; Turkcuer, Ibrahim; Kurt, Ozgur; Koseler, AylinBackground/Aim: Extracellular S100b effects are mediated by the receptor for advanced glycation end products (RAGE), which is the S100b membrane receptor. RAGE belongs to the immunoglobulin superfamily of cell surface molecules and serves as a multiligand receptor and is expressed in high abundance by alveolar type I (AT-I) cells in adult pulmonary tissue. This study aimed to provide an insight into the association between the severity of COVID19 disease and serum S100b levels during admission to the emergency department (ED). Patients and Methods: A total of 64 patients (34 mild casesItem Endoplasmic Reticulum Stress Markers in SARS-COV-2 Infection and Pneumonia: Case-Control Study(INT INST ANTICANCER RESEARCH, 2020-01-01) Koseler, Aylin; Sabirli, Ramazan; Goren, Tarik; Turkcuer, Ibrahim; Kurt, OzgurBackground/Aim: A novel human coronavirus, named SARS-COV-2, has recently caused thousands of deaths all around the world. Endoplasmic reticulum (ER) stress plays an important role in the development of diseases. Patients and Methods: We aimed to to investigate the relationship between ER stress markers in patients infected with SARS-COV-2 and patients with pneumonia. A total of 9 patients (4 patients diagnosed with pneumonia and 5 patients diagnosed with SARS-COV-2 infection) who admitted to the emergency Department with symptoms of pneumonia and SARS-COV-2 were included in the study. A total of 18 healthy individuals without any known chronic or acute disease and drug use were included as the healthy control group. Serum human glucose regulated protein 78 (GRP78), serum human C/EBP homologous protein (CHOP) and serum human phospho extracellular signal regulated kinase (PERK) levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: GRP78 levels were found to be significantly higher in SARS-COV-2 positive cases compared to individuals in other groups. Serum GRP78 level median value was statistically significantly higher in SARS-COV-2-positive group compared to the other groups (p=0.0003). Serum PERK level was statistically significantly higher in SARS-COV-2-positive pneumonia cases (p=0.046). Conclusion: An association was shown between GRP78 and SARS-COV-2 infection. Although a small number of patients was investigated, these results will be important and guide future treatments of SARS-COV-2.Item High GRP78 levels in Covid-19 infection: A case-control study(PERGAMON-ELSEVIER SCIENCE LTD, 2021-01-01) Sabirli, Ramazan; Koseler, Aylin; Goren, Tarik; Turkcuer, Ibrahim; Kurt, OzgurIntroduction: Covid-19 infection was declared a global pandemic by WHO on March 11, 2020. GRP78 protein is known to be involved in the intrusion of numerous viruses. Our current study tries to provide some insight into the variation of GRP78 protein levels in patients with Covid-19 (-) pneumonia, Covid-19 (+) pneumonia, and CT negative Covid-19 infection in comparison to the normal population through a larger number of cases. Materials and methods: 42 patients who have Covid-19 (-) pneumonia