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Öğe Association of HIF1α, BNIP3, and BNIP3L with Hypoxia-Related Metabolic Stress in Metabolic Syndrome(Mdpi, 2026) Kiran, Tugba Raika; Keskin, Lezan; Erdem, Mehmet; Guctekin, Zeynep; Inceoglu, FeyzaBackground and Objectives: Metabolic syndrome (MetS) is a complex condition marked by insulin resistance, central obesity, dyslipidemia, and chronic inflammation. Emerging evidence highlights the roles of hypoxia and mitochondrial stress in its pathophysiology. Hypoxia-inducible factor-1 alpha (HIF1 alpha) and the mitophagy-associated proteins BNIP3 and BNIP3L are key components of hypoxia-responsive mitochondrial stress signaling. This study aimed to evaluate the circulating levels of HIF1 alpha, BNIP3, and BNIP3L in MetS and to explore their associations with metabolic and inflammatory parameters. Materials and Methods: Serum concentrations of HIF1 alpha, BNIP3, and BNIP3L were measured by ELISA in 40 patients with MetS and 40 age and sex-matched controls. Biochemical, hematological, and anthropometric parameters were assessed, and receiver operating characteristic (ROC) analyses were performed to evaluate diagnostic performance. Results: Serum levels of HIF1 alpha, BNIP3, and BNIP3L levels were significantly higher in MetS patients compared with controls (p = 0.001). ROC analysis demonstrated strong diagnostic potential, particularly for BNIP3 (AUC = 0.928), followed by HIF1 alpha (AUC = 0.885) and BNIP3L (AUC = 0.770). These markers showed significant associations with metabolic indicators such as BMI, fasting glucose, triglycerides, and inflammatory markers. Conclusions: The coordinated upregulation of circulating HIF1 alpha, BNIP3, and BNIP3L in MetS is associated with metabolic dysregulation and systemic inflammation, reflecting alterations in hypoxia-responsive mitophagy-associated signaling rather than direct functional impairment of mitophagy. These findings support the potential relevance of these markers as indicators of metabolic stress in MetS. Further tissue-based and mechanistic studies are warranted to clarify their role in disease pathophysiology.Öğe Carbonic Anhydrase IX as a Marker of Disease Severity in Obstructive Sleep Apnea(Mdpi, 2022) Geckil, Aysegul Altintop; Kiran, Tugba Raika; Berber, Nurcan Kirici; Otlu, Onder; Erdem, Mehmet; In, ErdalBackground and Objectives: Carbonic anhydrase (CA) enzymes are a family of metalloenzymes that contain a zinc ion in their active sites. CA enzymes have been implied in important situations such as CO2 transport, pH regulation, and oncogenesis. CA-IX is a transmembrane glycoprotein and stimulates the expression of hypoxia-inducible factor-1 (HIF-1) CA-IX. This study aimed to determine serum CA-IX levels in OSA patients in whom intermittent hypoxia is important and to investigate the relationship between serum CA-IX levels and disease severity. Materials and Methods: The study included 88 people who applied to Malatya Turgut Ozal University Training and Research Hospital Sleep Disorders Center without a history of respiratory disease, malignancy, and smoking. Patients were divided into three groups: control (AHI < 5, n = 31), mild-moderate OSA (AHI = 5-30, n = 27) and severe OSA (AHI > 30, n = 30). The analysis of the data included in the research was carried out with the SPSS (IBM Statistics 25, NY, USA). The Shapiro-Wilk Test was used to check whether the data included in the study had a normal distribution. Comparisons were made with ANOVA in multivariate groups and the t-test in bivariate groups. ANCOVA was applied to determine the effect of the CA-IX parameter for OSA by controlling the effect of independent variables. The differentiation in CA-IX and OSA groups was analyzed regardless of BMI, age, gender, and laboratory variables. ROC analysis was applied to determine the parameter cut-off point. Sensitivity, specificity, and cut-off were calculated, and the area under the curve (AUC) value was calculated. Results: Serum CA-IX levels were 126.3 +/- 24.5 pg/mL in the control group, 184.6 +/- 59.1 pg/mL in the mild-moderate OSA group, and 332.0 +/- 39.7 pg/mL in the severe OSA group. Serum CA-IX levels were found to be higher in the severe OSA group compared to the mild-moderate OSA group and control group and higher in the mild-moderate OSA group compared to the control group (p < 0.001, p < 0.001, p < 0.001, respectively). In addition, a negative correlation between CA-IX and minimum SaO(2) and mean SaOI(2) (r = -0.371, p = 0.004; r = -0.319, p = 0.017, respectively). A positive correlation between CA-IX and desaturation index (CT90) was found (r = 0.369, p = 0.005). A positive correlation was found between CA-IX and CRP (r = 0.340, p = 0.010). When evaluated by ROC curve analysis, the area under the curve (AUC) value was determined as 0.940 (95% CI 0.322-0.557; p < 0.001). When the cut-off value for CA-IX was taken as 254.5 pg/mL, it was found to have 96.7% sensitivity and 94.8% specificity in demonstrating severe OSA. Conclusions: Our study found that serum CA-IX value was higher in OSA patients than in control patients, and this elevation was associated with hypoxemia and inflammation. CA-IX value can be a fast, precise, and useful biomarker to predict OSA.Öğe Changes in oxidative stress markers in pediatric burn injury over a 1-week period(De Gruyter Poland Sp Z O O, 2023) Harma, Birsen; Kiran, Tugba RaikaThe importance of oxidative stress in the pathogenesis of burn injuries has been shown in various studies. Glutathione (GSH) and thiols have important roles in antioxidant protection and detoxification. The study aimed to investigate the relationship between pediatric burn trauma and GSH and thiol homeostasis. Twenty-nine children with thermal-burn injuries and 29 healthy peers are included in this prospective randomized study. Children with burn wounds of 15-25% of total body surface area (TBSA) were included in the patient group. The control group was created from healthy peers of both sexes. All children were 1-10 years of age. Serum GSH, oxidized glutathione (GSSG), redox ratio (GSH/GSSG), and thiol-disulfide (SS) tests were conducted in both groups, and the changes between admission and day 7 were analyzed in patients with burn injuries. The mean age was 4.09 +/- 2.54 years for the patient group and 4.28 +/- 2.55 years for the controls (p > 0.05). Total thiol (TT), native thiol (SH), and SS levels were significantly lower in the patient group than in the controls (TT = 291.69 +/- 7.93 vs 346.79 +/- 18.89 mu mol/L, SH = 259.39 +/- 7.90 vs 297.64 +/- 12.81 mu mol/L, SS = 16.15 +/- 4.68 vs 24.58 +/- 5.76 mu mol/L; p < 0.001). SH/TT ratio was higher in the patient group (89.05 +/- 3.00 vs 85.93 +/- 3.01 mu mol/L; p < 0.001). The SS/SH and SS/TT ratios were significantly lower in the patient group, while the SH/TT ratio was significantly higher (p < 0.001). The patients had significantly decreased GSH levels (26.12 +/- 2.42 vs 34.80 +/- 2.26) and GSH/GSSG ratios (1.69 +/- 0.12 vs 3.05 +/- 0.29) and increased GSSG levels (16.09 +/- 0.34 vs 11.48 +/- 1.17, p < 0.001 for all). The GSSG level and GSSG/SH and GSSG/TT ratios were higher in the patient group than in the controls while the SH, TT, and SS levels, and SS/SH and SS/TT ratios were lower in the patient group. Analysis of serum GSSG levels, and ratios with SH and TT homeostasis, might be useful in order to determine burn damage in children.Öğe Could TREM-1 be a novel marker in the diagnosis of fibromyalgia?: A cross-sectional study(Lippincott Williams & Wilkins, 2024) Baykara, Rabia Aydogan; Kiran, Tugba Raika; Otlu, Onder; Erdem, Mehmet; Tas, Nevsun PihtiliTriggering receptors expressed on myeloid cells-1 (TREM-1) are transmembrane molecules expressed in cells of the immune system. Activation of TREM-1 leads to the release of pro-inflammatory mediators, which act as amplifiers of inflammation and thereby contribute to the pathogenesis of various diseases, whether inflammatory or not. This study explored the role of TREM-1 in the etiopathogenic context of fibromyalgia syndrome (FMS) and its association with disease activity. This randomized controlled and observational study included 45 patients diagnosed with FMS according to the 2016 American College of Rheumatology criteria. Serum TREM-1 levels were assessed using ELISA, and disease activity was measured using various scales such as the fibromyalgia impact questionnaire (FIQ). Patients were divided into 2 groups according to disease severity based on the FIQ score. Compared to a control group of 46 healthy individuals, patients with FMS exhibited significantly elevated concentrations of TREM-1 (mean +/- SD = 216.97 pg/mL +/- 16.04), P < .05. The FIQ, Pittsburgh sleep quality index, hospital anxiety and depression scale, fatigue severity scale, and visual analog scale, which confirm symptoms such as pain, disease severity, sleep disturbance, depression, anxiety, and fatigue seen in FMS was significantly correlated with TREM-1 level (P < .001). The optimal threshold value for TREM-1 to disease activity was determined to be 182.250, showing (area under the curve) (CI (95%)): [0.940] (0.887-0.993), a sensitivity of 97% and a specificity of 89% according to the receiver operating characteristic analysis. The positive correlation of TREM-1 with various symptom severity scales and hematological inflammatory indices may be a suitable biomarker for the diagnosis of FMS and a potential therapeutic target.Öğe Diagnostic Value of Galectin-3 in Exacerbations of Chronic Obstructive Pulmonary Disease(Mdpi, 2024) Berber, Nurcan Kirici; Atli, Siahmet; Geckil, Ayseguel Altintop; Erdem, Mehmet; Kiran, Tugba Raika; Otlu, Onder; In, ErdalBackground and Objectives: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by acute exacerbations. Systemic inflammation and oxidative stress play an important role in the pathogenesis of COPD. Exacerbations in COPD reduce the quality of life and are associated with rapid disease progression. Galectin-3 is a beta-galactoside-binding lectin of approximately 30 kDa with pro-inflammatory and pro-fibrotic properties. This study aims to analyze the efficacy of serum galectin-3 in predicting exacerbations in COPD patients. Materials and Methods: Baseline demographic and clinical characteristics of all patients were recorded and blood samples were collected. A total of 58 consecutive COPD patients, including 28 patients (19 male and 9 female) with stable COPD and 30 patients (23 male and 7 female) with acute exacerbation of COPD (AECOPD), were included in the study. Results: Serum galectin-3 levels were significantly higher in the AECOPD group compared to the stable COPD group. A logistic regression analysis revealed that increased galectin-3 levels and disease duration were independent predictors of COPD exacerbation (OR = 5.322, 95% CI: 1.178-24.052, p = 0.03; and OR = 1.297, 95% CI: 1.028-1.635, p = 0.028; respectively). Conclusions: The results of our study demonstrated that Galectin-3 was a strong and independent predictor of exacerbations in COPD patients.Öğe Efficacy of serum apelin and galectin-3 as potential predictors of mortality in severe COVID-19 patients(Wiley, 2023) Berber, Nurcan Kirici; Geckil, Aysegul Altintop; Altan, Nazife Ozge; Kiran, Tugba Raika; Otlu, Onder; Erdem, Mehmet; In, ErdalApelin is a cardioprotective biomarker while galectin-3 is a pro-inflammatory and profibrotic biomarker. Endothelial dysfunction, hyperinflammation, and pulmonary fibrosis are key mechanisms that contribute to the development of adverse outcomes in Coronavirus disease 2019 (COVID-19) infection. This study aims to analyze the prognostic value of serum apelin and galectin-3 levels to early predict patients at high risk of mortality in patients hospitalized for severe COVID-19 pneumonia. The study included 78 severe COVID-19 patients and 40 healthy controls. The COVID-19 patients were divided into two groups, survivors and nonsurvivors, according to their in-hospital mortality status. Basic demographic and clinical data of all patients were collected, and blood samples were taken before treatment. In our study, serum apelin levels were determined to be significantly lower in both nonsurvivor and survivor COVID-19 patients compared to the control subjects (for both groups, p < 0.001). However, serum apelin levels were similar in survivor and nonsurvivor COVID-19 patients (p > 0.05). Serum galectin-3 levels were determined to be higher in a statistically significant way in nonsurvivors compared to survivors and controls (for both groups; p < 0.001). Additionally, serum galectin-3 levels were significantly higher in the survivor patients compared to the control subjects (p < 0.001). Positive correlations were observed between galectin-3 and age, ferritin, CK-MB and NT-proBNP variables (r = 0.32, p = 0.004; r = 0.24, p = 0.04; r = 0.24, p = 0.03; and r = 0.33, p = 0.003, respectively) while a negative correlation was observed between galectin-3 and albumin (r = -0.31, p = 0.006). Multiple logistic regression analysis revealed that galectin-3 was an independent predictor of mortality in COVID-19 patients (odds ratio [OR] = 2.272, 95% confidence interval [CI] = 1.106-4.667; p = 0.025). When the threshold value for galectin-3 was regarded as 2.8 ng/ml, it was discovered to predict mortality with 80% sensitivity and 57% specificity (area under the curve = 0.738, 95% CI = 0.611-0.866, p = 0.002). Galectin-3 might be a simple, useful, and prognostic biomarker that can be utilized to predict patients who are at high risk of mortality in severe COVID-19 patients.Öğe Endoplasmic reticulum stress and oxidative imbalance is the missing link in fibromyalgia pathophysiology(Nature Portfolio, 2025) Otlu, Onder; Kiran, Tugba Raika; Baykara, Rabia Aydogan; Erdem, Mehmet; Inceoglu, FeyzaFibromyalgia syndrome (FMS) is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, and cognitive dysfunction. Although its exact pathophysiology remains unclear, emerging evidence suggests that endoplasmic reticulum (ER) stress and oxidative stress play significant roles in its development. This study aimed to investigate the involvement of ER stress in FMS by evaluating key ER stress markers and oxidative stress parameters in patients with FMS. A total of forty-four FMS patients and matched healthy controls were included in the study. Serum levels of ER stress markers were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, oxidative stress markers were assessed to examine their relationship with ER stress in FMS. The ER stress parameters were significantly higher in the FMS group compared to controls. Furthermore, oxidative stress markers were elevated, reinforcing the interconnection between ER stress and oxidative stress in FMS pathogenesis. These findings suggest that ER stress plays a crucial role in the pathophysiology of FMS, likely contributing to disease progression through oxidative stress-related mechanisms. Targeting ER stress and oxidative stress pathways may represent a promising therapeutic strategy for FMS management. Future studies should focus on large-scale clinical investigations to further elucidate these pathways and develop effective treatment approaches.Öğe Evaluation of Oxidative Stress and Endothelial Dysfunction in COVID-19 Patients(Mdpi, 2024) Berber, Nurcan Kirici; Kurt, Osman; Geckil, Ayseguel Altintop; Erdem, Mehmet; Kiran, Tugba Raika; Otlu, Onder; In, ErdalBackground and Objectives: Heat shock proteins (HSPs) are stress proteins. The endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethyl arginine (ADMA) is a mediator of endothelial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes endothelial dysfunction and coagulopathy through severe inflammation and oxidative stress. Using these markers, we analyzed the prognostic value of serum ADMA and HSP-90 levels for early prediction of severe coronavirus disease (COVID-19) patients. Materials and Methods: A total of 76 COVID-19 patients and 35 healthy control subjects were included in this case-control study. COVID-19 patients were divided into two groups: mild and severe. Results: Serum ADMA and HSP-90 levels were significantly higher in the COVID-19 patients compared to the control subjects (p < 0.001). Additionally, serum ADMA and HSP-90 levels were determined to be higher in a statistically significant way in severe COVID-19 compared to mild COVID-19 (p < 0.001). Univariable logistic regression analysis revealed that ADMA and HSP-90, respectively, were independent predictors of severe disease in COVID-19 patients (ADMA (OR = 1.099, 95% CI = 1.048-1.152, p < 0.001) and HSP-90 (OR = 5.296, 95% CI = 1.719-16.316, p = 0.004)). When the cut-off value for ADMA was determined as 208.94 for the prediction of the severity of COVID-19 patients, the sensitivity was 72.9% and the specificity was 100% (AUC = 0.938, 95%CI = 0.858-0.981, p < 0.001). When the cut-off value for HSP-90 was determined as 12.68 for the prediction of the severity of COVID-19 patients, the sensitivity was 88.1% and the specificity was 100% (AUC = 0.975, 95% CI= 0.910-0.997, p < 0.001). Conclusions: Increased levels of Heat shock proteins-90 (HSP-90) and ADMA were positively correlated with increased endothelial damage in COVID-19 patients, suggesting that treatments focused on preventing and improving endothelial dysfunction could significantly improve the outcomes and reduce the mortality rate of COVID-19. ADMA and HSP-90 might be simple, useful, and prognostic biomarkers that can be utilized to predict patients who are at high risk of severe disease due to COVID-19.Öğe Evaluation of second trimester plasma lipoxin A4, VEGFR-1, IL-6, and TNF-a levels in pregnant women with gestational diabetes mellitus(De Gruyter Poland Sp Z O O, 2023) Kiran, Tugba Raika; Melekoglu, Rauf; Otlu, Onder; Inceoglu, Feyza; Karabulut, Ercan; Erenler, Ayse SebnemIn this study, our objective was to explore the association between gestational diabetes mellitus (GDM) and second trimester maternal plasma levels of lipoxin A4 (LXA4), along with proinflammatory markers such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-a), and the anti-angiogenic factor vascular endothelial growth factor receptor 1 (VEGFR-1) in pregnant women. The study included a cohort of 30 pregnant women with GDM and a control group of 30 normoglycaemic pregnant women matched for age, body mass index, and gestational age. Plasma samples were collected and analysed by enzyme-linked immunosorbent assay to assess specific biomarkers. The GDM group had significantly lower levels of LXA4 and higher levels of TNF-a and VEGFR-1 compared to the control group (p = 0.038, p = 0.025, and p = 0.002, respectively). A statistically significant decrease in the LXA4/TNF-a ratio was observed in the GDM group (p = 0.004). The results suggest that each unit decrease in the LXA4/TNF-a ratio is associated with a 1.280-fold increase in the risk of GDM. These findings suggest a potential diagnostic role for the LXA4/TNFa ratio as a marker for women with GDM. This work provides new insights into the pathogenesis of GDM and highlights the important interplay between inflammation and metabolic dysregulation.Öğe Evaluation of vascular tone in patients with menorrhagia: the role of apelin and norepinephrine(Walter de Gruyter Gmbh, 2026) Guctekin, Zeynep; Erdem, Mehmet; Dogan, Umran Karabulut; Yildirim, Engin; Kiran, Tugba RaikaObjectives Menorrhagia, characterized by excessive menstrual bleeding, impacts 30 % of women of childbearing period and is frequently linked to anemia and discomfort in the pelvic region. Understanding the vascular and hormonal mechanisms underlying this condition could aid in developing non-surgical treatment options. This research focused on exploring the role of apelin and norepinephrine (NE), along with nitric oxide (NO) and prostacyclin (PGI2), in the pathophysiology of menorrhagia. Methods The study included 44 women diagnosed with menorrhagia and 44 healthy controls. Blood specimens were taken on the 2nd or 3rd day of menstruation, and serum specimens were prepared. The levels of apelin, NE, NO, and PGI2 were determined using commercially available ELISA kits. Furthermore, standard biochemical analyses were conducted on all specimens. Results Apelin and NE levels were significantly reduced in the menorrhagia group compared to control group (p<0.05). The comparison of NO and PGI2 levels showed no statistically significant difference between the menorrhagia and control groups (p>0.05). In the menorrhagia group, total cholesterol, iron-binding capacity, platelet count, and FSH concentrations were markedly higher than those in control individuals, conversely, albumin, iron, hemoglobin, MCV, hematocrit, and progesterone levels were notably reduced (p<0.05) .Conclusions The study identified apelin and NE as moderately discriminative markers in menorrhagia and suggested that these markers could potentially contribute to impaired vasoconstriction and excessive menstrual bleeding. Future research should focus on evaluating biomarkers across different menstrual phases and exploring new therapeutic strategies for uterine protection.Öğe Interleukin-37 and interleukin-39 as novel immunometabolic biomarkers in metabolic syndrome: A cross-sectional study(Lippincott Williams & Wilkins, 2026) Keskin, Lezan; Kiran, Tugba Raika; Erdem, Mehmet; Inceoglu, FeyzaMetabolic syndrome (MetS) is characterized by abdominal obesity, dyslipidemia, hypertension, and insulin resistance, all driven by chronic low-grade inflammation. This study aimed to evaluate serum interleukin-37 (IL-37) and interleukin-39 (IL-39) levels as potential immunometabolic biomarkers in MetS. Eighty adults (40 MetS patients, 40 healthy controls) were enrolled based on NCEP ATP III criteria. Anthropometric, biochemical, and hormonal parameters were assessed. Serum IL-37 and IL-39 concentrations were measured using ELISA. Statistical analyses included t-tests, Pearson correlations, logistic regression, and receiver operating characteristic curve analysis. Both IL-37 and IL-39 levels were significantly elevated in MetS compared with controls (P <.001). Logistic regression revealed that each 1 pg/mL increase in IL-37 and IL-39 was associated with 1.01-fold (P = .017) and 1.06-fold (P = .001) higher odds of MetS, respectively. receiver operating characteristic analysis showed excellent discriminative ability for IL-39 (AUC = 0.96; 95% confidence intervals: 0.91-1.00) and good accuracy for IL-37 (AUC = 0.82; 95% confidence intervals: 0.73-0.91). Among classical parameters, waist circumference (AUC = 1.00), TG (AUC = 0.93), and fasting glucose (AUC = 0.88) showed the strongest diagnostic power. HDL cholesterol exhibited inverse association (AUC = 0.83), while systolic and diastolic blood pressure showed moderate accuracy (AUC = 0.85 and 0.71, respectively). IL-37 and IL-39 were elevated in individuals with MetS and showed strong discriminative performance, particularly IL-39. These cytokines may reflect underlying immunometabolic alterations and could provide complementary information alongside established metabolic parameters. However, given the cross-sectional design and modest sample size, these findings should be considered exploratory and require validation in larger, longitudinal studies to determine their clinical relevance.Öğe Oxidative stress and antioxidants in health and disease(Walter de Gruyter Gmbh, 2023) Kiran, Tugba Raika; Otlu, Onder; Karabulut, Aysun BayThe increase in the formation of reactive oxygen and reactive nitrogen species of endogenous or exogenous origin causes oxidative stress due to pro-oxidant and antioxidant imbalance that causes cellular damage in metabolism. This can increase inflammation of cells, apoptosis and necrosis, damage to DNA base damage, DNA and protein cross-links, lipid membrane peroxidation, and mitochondrial dysfunction. Antioxidants can be described as a system that protects biomolecules and the organism against the harmful effects of free radicals, reduces or repairs the damage done by reactive oxygen species (ROS) to the target molecule, and this is called antioxidant defense. It is known that the mechanisms caused by the increase in ROS resulting from oxidative stress are positively related to the pathology of many diseases such as cancer, metabolic syndrome, atherosclerosis, malaria, Alzheimer's disease, rheumatoid arthritis, neurodegenerative diseases and preeclampsia.Öğe Oxygen regulated protein 150 can be considered as a severity indicator in obstructive sleep apnea(Nature Portfolio, 2025) Otlu, Onder; Erdem, Mehmet; Kiran, Tugba Raika; Inceoglu, Feyza; Geckil, Aysegul Altintop; Berber, Nurcan Kirici; In, ErdalOxygen-regulated protein 150 (ORP150) is a chaperone found in the endoplasmic reticulum (ER) induced by ER stress, oxidative stress, glutamate toxicity, ischemia, and hypoxia. Increased expression of ORP150 protects the cells by stopping ER stress, maintaining calcium balance, and delaying apoptosis. In this study, we aim to investigate serum ORP150 amount in patients with different severity levels of obstructive sleep apnea (OSA). Forty-nine patients (25 of severe and 24 of mild-moderate), and 23 healthy controls were included in the study. Routine biochemical measurements and serum ORP150 measurements of all groups and sleep quality measurements of OSA groups were obtained. ELISA was used to measure ORP150 levels in serum samples. In addition, ROC analysis was performed to determine the diagnostic power of the ORP150 parameter. There are significant differences between all three groups in terms of ORP150 values (severe OSA: 8.03 +/- 0.4 ng/mL; mild-moderate OSA: 5.54 +/- 0.47 ng/mL; control: 4.41 +/- 0.25 ng/mL, p < 0.017). The highest ORP150 level belongs to the severe OSA group and there is a direct correlation between the severity of the disease and ORP150 levels. ORP150 value is a distinguishing parameter for OSA and the cut-off value of ORP150 was observed as 7.14 ng/mL. We concluded that serum ORP150 levels can be a differential diagnostic parameter in OSA patients and that disease severity can be determined by serum ORP150 measurement.Öğe R 2-adrenoceptor agonist formoterol attenuates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in microglia through enhancing IκBα/NF-κB κ B α /NF- κ B inhibition, SQSTM1/p62-dependent selective autophagy and ESCRT-III-mediated plasma membrane repair(Academic Press Inc Elsevier Science, 2024) Erdem, Mehmet; Erdem, Seniz; Alver, Ahmet; Kiran, Tugba Raika; Karahan, Sueleyman CanerMicroglia are immune cells that play important roles in the formation of the innate immune response within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiple protein complex that is crucial for innate immunity, and excessive activation of the inflammasome for various reasons contributes to the pathogenesis of neurodegenerative diseases (NDs). R2-adrenoceptor 2-adrenoceptor agonists have become the focus of attention in studies on NDs due to the high synthesis of R2-adrenoceptors 2-adrenoceptors in the central nervous system (CNS). Promising results have been obtained from these studies targeting antiinflammatory and neuroprotective effects. Formoterol is an effective, safe for long-term use, and FDA- approved R2-adrenoceptor 2-adrenoceptor agonist with demonstrated anti-inflammatory features in the CNS. In this study, we researched the effects of formoterol on LPS/ATP-stimulated NLRP3 inflammasome activation, pyroptosis, NF-kappa B, autophagy, and ESCRT-III-mediated plasma membrane repair pathways in the N9 microglia cells. The results showed that formoterol, through the I kappa B alpha/NF-kappa B axis, significantly inhibited NLRP3 inflammasome activation, reduced the level of active caspase-1, secretion of IL-1R and IL-18 proinflammatory cytokine levels, and the levels of pyroptosis. Additionally, we showed that formoterol activates autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair, which are significant pathways in the inhibition of NLRP3 inflammasome activation and pyroptosis. Our study suggests that formoterol efficaciously prevents the NLRP3 inflammasome activation and pyroptosis in microglial cells regulation through I kappa B alpha/NF-kappa B, autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair.Öğe Response: The role of carbonic anhydrase I and II enzymes in the pathogenesis of gestational diabetes mellitus and their relationship with oxidative stress(Wiley, 2026) Melekoglu, Rauf; Erenler, Ayse Sebnem; Kiran, Tugba Raika; Inceoglu, Feyza; Alkan Uckun, Aysel[Abstract Not Available]Öğe Significant correlation between serum DOTL1 levels and pain intensity, sensitivity, and psychological distress in women with fibromyalgia(Lippincott Williams & Wilkins, 2025) Erdem, Mehmet; Kiran, Tugba Raika; Otlu, Onder; Baykara, Rabia Aydogan; Inceoglu, FeyzaDisruptor of telomeric silencing 1-like (DOT1L) is a protein involved in epigenetic regulation, as well as in the Wnt and hypoxia signaling pathways. DOT1L has been found to play a role in the pathogenesis of various diseases associated with these pathways. In this study, it was aimed to determine serum DOT1L levels in patients with fibromyalgia (FM) and its association with disease activity. Forty-eight patients diagnosed with FM according to the 2016 American College of Rheumatology criteria and 48 healthy controls were included in the study. Disease activity was measured using clinical questionnaires (Fibromyalgia Impact Questionnaire [FIQ], Visual Analog Scale [VAS], Widespread Pain Index [WPI], Symptom Severity Score [SSS], Pittsburgh Sleep Quality Index [PSQI], Fatigue Severity Scale [FSS], Hospital Anxiety Scale [HAS] and Hospital Depression Scale [HDS]) and DOT1L levels were assessed using Enzyme-Linked ImmunoSorbent Assay in all serum samples. Additionally, routine biochemical analyses were performed. Pain duration, FIQ, VAS, WPI, SSS, PSQI, FSS, HAS, and HDS were found to be statistically significant higher in FM compared to the control group (P = .001). Compared with the control group (0.53 +/- 0.12 ng/mL), DOT1L concentrations were significantly higher in patients with FM (1.47 +/- 0.13 ng/mL; P = .001). In the FM group, DOT1L levels also showed a positive correlation with the results of the all the clinical questionnaires (P = .001). It was found that the DOT1L measurement value has a statistically significant effect in predicting the difference between the FM and control groups (P = .022). When the cutoff value for DOT1L was set at 0.315 ng/mL, it was found to have 79% sensitivity and 71.7% specificity in detecting FM. This study highlights the potential of DOT1L as a valuable biomarker for FM diagnosis.Öğe The effects of disease severity and comorbidity on oxidative stress biomarkers in obstructive sleep apnea(Springer Heidelberg, 2024) Kiran, Tugba Raika; Otlu, Onder; Erdem, Mehmet; Geckil, Aysegul Altintop; Berber, Nurcan Kirici; In, ErdalPurposeIschemia-modified albumin (IMA), total oxidant status (TOS), and total antioxidant status (TAS) are biomarkers used to evaluate oxidative stress status in various diseases including obstructive sleep apnea (OSA). In this study, we investigated the effects of disease severity and comorbidity on IMA, TOS and TAS levels in OSA.MethodsPatients with severe OSA (no-comorbidity, one comorbidity, and multiple comorbidities) and mild-moderate OSA (no-comorbidity, one and multiple comorbidities), and healthy controls were included in the study. Polysomnography was applied to all cases and blood samples were taken from each participant at the same time of day. ELISA was used to measure IMA levels in serum samples and colorimetric commercial kits were used to perform TOS and TAS analyses. In addition, routine biochemical analyses were performed on all serum samples.ResultsA total of 74 patients and 14 healthy controls were enrolled. There was no statistically significant difference between the disease groups according to gender, smoking status, age, body mass index (BMI), HDL, T3, T4, TSH, and B12 (p > 0.05). As the severity of OSA and comorbidities increased, IMA, TOS, apnea-hypopnea index (AHI), desaturation index (T90), cholesterol, LDL, triglyceride, AST, and CRP values increased significantly (p < 0.05). On the other hand, TAS, minimum desaturation, and mean desaturation values decreased significantly (p < 0.05).ConclusionsWe concluded that IMA, TOS, and TAS levels may indicate OSA-related oxidative stress, but as the severity of OSA increases and with the presence of comorbidity, IMA and TOS levels may increase and TAS levels decrease. These findings suggest that disease severity and presence/absence of comorbidity should be considered in studies on OSA.Öğe The role of carbonic anhydrase I and II enzymes in the pathogenesis of gestational diabetes mellitus and their relationship with oxidative stress(Wiley, 2026) Melekoglu, Rauf; Erenler, Ayse Sebnem; Kiran, Tugba Raika; Inceoglu, Feyza; Alkan Uckun, AyselObjective Gestational diabetes mellitus (GDM) is a hyperglycemic condition that develops during pregnancy and poses significant risks to maternal and fetal health. Oxidative stress plays a crucial role in the pathogenesis of GDM by disrupting insulin signaling pathways and contributing to beta-cell dysfunction. Carbonic anhydrase (CA) enzymes, particularly CA-I and CA-II, are involved in pH regulation and metabolic homeostasis. However, the relationship between oxidative stress and CA enzyme activity in GDM remains unclear. The aim of the present study was to evaluate CA-I and CA-II levels and their association with oxidative stress parameters in GDM patients. Methods This case-control study included 30 pregnant women with GDM and 30 healthy pregnant controls. Baseline characteristics were fully reported; differences between groups were examined using covariate-adjusted analyses. Serum levels of CA-I, CA-II, malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant capacity (TAC) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis was performed using SPSS 25, with significance set at P < 0.05. Results CA-I and CA-II levels were significantly higher in the GDM group compared to control (P < 0.05). MDA and TOS levels were also elevated in GDM patients, indicating increased oxidative stress, whereas TAC levels were significantly lower (P < 0.05). Receiver operating characteristic (ROC) analysis revealed that CA-I, CA-II, MDA, and TOS exhibited strong discriminatory power in differentiating GDM patients from healthy controls. In a multivariable linear regression adjusting for age, body mass index (BMI), gestational age at sampling, and parity, GDM was associated with higher CA-I (beta = 3.1, 95% confidence interval [CI]: 1.6-4.6) and CA-II (beta = 2.4, 1.1-3.7), higher MDA (beta = 0.27 per 0.1-unit) and TOS (beta = 4.1 per unit), and lower TAC (beta = -0.22 per 0.1-unit; all P <= 0.004). In logistic regression, CA-I, CA-II, MDA, and TOS independently increased the odds of GDM, while TAC was inversely associated (adjusted odds ratios [ORs] 1.28, 1.17, 1.15, 1.05, and 0.87, respectively), with excellent model performance (area under the curve [AUC] 0.86; Hosmer-Lemeshow P = 0.67). Conclusion Increased CA-I and CA-II levels in GDM patients suggest a potential role for CA enzymes in the metabolic dysregulation associated with GDM. The strong correlation between oxidative stress markers and CA enzyme activity highlights their potential as diagnostic and prognostic biomarkers for GDM. Future studies should explore the mechanistic pathways linking CA enzymes with oxidative stress and insulin resistance to identify novel therapeutic targets.Öğe Unveiling the significance of Netrin-1 and Netrin-4 in metabolic syndrome(Nature Portfolio, 2026) Kiran, Tugba Raika; Ayyildiz, Gamze; Keskin, Lezan; Erdem, MehmetMetabolic syndrome (MetS) is characterized by insulin resistance, dyslipidemia, hyperglycemia, and chronic low-grade inflammation. This study aimed to evaluate serum levels of Netrin-1 (NTN1) and Netrin-4 (NTN4) in individuals with MetS and to explore their associations with metabolic and inflammatory parameters. Forty patients with MetS (diagnosed according to the NCEP ATP III criteria) and forty age- and sex-matched healthy controls were included. Serum NTN1 and NTN4 concentrations were measured using enzyme-linked immunosorbent assay (ELISA), together with biochemical and hematological analyses. MetS patients exhibited significantly higher NTN1 (146.66 (54.79) pg/mL) and NTN4 (176.76 +/- 41.65 pg/mL) levels than controls (110.343 (27.14) pg/mL and 133.10 +/- 32.17 pg/mL, respectively; p = 0.001). Binary logistic regression identified NTN4 as a significant variable associated with MetS (p = 0.017), whereas NTN1 did not remain significant after adjustment for other factors. Both markers showed positive correlations with body mass index, fasting glucose, HbA1c, triglycerides, and CRP, and negative correlations with HDL cholesterol (p = 0.001). Receiver operating characteristic (ROC) analysis identified optimal cut-off values for discriminating MetS, with NTN1 >= 122.99 pg/mL yielding 82.5% sensitivity and NTN4 >= 186.49 pg/mL showing 97.5% specificity. Elevated NTN1 and NTN4 levels were associated with the metabolic and inflammatory alterations characteristic of MetS. NTN4, and to a lesser extent NTN1, were associated with systemic metabolic imbalance.Öğe Vascular imbalance in polycystic ovary syndrome: Insights into endothelial dysfunction(Public Library Science, 2025) Kiran, Tugba Raika; Erdem, Mehmet; Yildirim, Engin; Inceoglu, FeyzaPolycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder associated with vascular dysfunction and increased cardiovascular risk. This study aims to investigate the dysregulation of vascular tone in PCOS, focusing on the imbalance between vasodilators (nitric oxide [NO] and apelin) and vasoconstrictors (noradrenaline and reduced prostacyclin). By examining these factors, the study seeks to elucidate their contribution to endothelial dysfunction and cardiovascular complications in PCOS patients. Forty-four patients diagnosed with PCOS according to the 2003 Rotterdam Criteria, along with 44 healthy controls, were included in the study. Ultrasound evaluations were performed on all volunteers. Serum NO, apelin, noradrenaline, and prostacyclin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Additionally, routine biochemical, hormonal, and glycated hemoglobin analyses were conducted on all samples. There was no statistically significant difference between the PCOS and control groups in terms of marital status, age, and body mass index (BMI) (p > 0.05). Compared to the control group (83.85 +/- 22.65 mu mol/L, 190.88 +/- 16.44 ng/L, and 24.63 +/- 4.59 ng/L, respectively), NO, apelin, and noradrenaline concentrations were significantly higher in patients with PCOS (104.35 +/- 44.96 mu mol/L, 379.57 +/- 40.11 ng/L, and 27.48 +/- 5.36 ng/L, respectively) (p < 0.01). In contrast, prostacyclin concentrations were significantly lower in patients with PCOS (5.85 +/- 1.28 ng/L) compared to the control group (6.78 +/- 1.99 ng/L) (p = 0.011). Additionally, a statistically significant difference was found between the PCOS and control groups in FSH, LH, testosterone, SHBG, glucose, and HDL levels (p < 0.05). The disrupted balance between vasodilation and vasoconstriction in PCOS, driven by altered levels of NO, apelin, noradrenaline, and prostacyclin, contributes to endothelial dysfunction and increased cardiovascular risk. These molecular disturbances underline the need for targeted therapeutic strategies aimed at restoring vascular homeostasis in PCOS patients.
