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Öğe Acil Serviste Miyokard Enfarktüsünde Hemogram Parametrelerinin Tanısal Değeri(Acil Tıp Uzmanları Derneği, 2026) Yumrutepe, Sevgi; Erdem, Mehmet; Kıran, Tuğba Raika; İnceoğlu, Feyza; Özkan, Asiye; Nogay, SüleymanAmaç: Bu çalışmada, acil servise göğüs ağrısı ile başvuran hastalarda miyokard enfarktüsünün tanısında lökosit sayısı, lökosit-trombosit oranı ve nötrofil-trombosit oranı gibi hemogram temelli inflamatuvar parametrelerin tanısal değerinin değerlendirilmesi amaçlandı. Gereç ve Yöntem: Ocak–Şubat 2025 tarihleri arasında acil servise göğüs ağrısı ile başvuran, 18 yaş üzeri 60 miyokard enfarktüslü ve 60 miyokard enfarktüsü olmayan hasta retrospektif olarak incelendi. Hemogram, biyokimya, elektrokardiyografi ve kreatin kinaz-MB değerleri değerlendirildi. Lökosit sayısı, lökosit-trombosit oranı ve nötrofil-trombosit oranı iki grup arasında karşılaştırıldı. Tanısal performans alıcı işletim karakteristiği analizi ile değerlendirildi ve optimal eşik değerler Youden indeksi kullanılarak belirlendi. Bulgular: Glukoz, kreatin kinaz-MB, lökosit sayısı, nötrofil sayısı, lökosit-trombosit oranı ve nötrofil-trombosit oranı miyokard enfarktüsü grubunda kontrol grubuna göre anlamlı derecede daha yüksek bulundu (p<0.001). Alıcı işletim karakteristiği analizinde, lökosit-trombosit oranı en yüksek tanısal doğruluğa sahip olup eğri altında kalan alan değeri 0.732 olarak saptandı. Bu parametre için kesim değeri 0.0365 olup duyarlılık %71.7 ve özgüllük %66.7 idi. Sonuç: Hızlı, düşük maliyetli ve kolay erişilebilir hemogram parametreleri miyokard enfarktüsünün tanısında anlamlı katkı sağlayabilir. Özellikle lökosit-trombosit oranı, troponin sonuçları beklenirken klinik karar verme sürecini destekleyebilecek pratik bir biyobelirteç olabilir.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 Brain-Derived Neurotrophic Factor Deficiency Exacerbates Innate Immune Responses by Enhancing NLRP3 Inflammasome Activation and GSDMD-Mediated Pyroptosis in Mice(Mdpi, 2026) Erdem, Seniz; Saglam, Neslihan; Sahin, Elif; Erdem, Mehmet; Abidin, Ismail; Alver, AhmetBackground and Objectives: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a key innate immune complex, and its aberrant activation contributes to metabolic and neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with anti-inflammatory and metabolic regulatory functions, but its role in NLRP3 inflammasome activation and gasdermin D (GSDMD)-mediated pyroptosis remains unclear. The aim of this study was to investigate the effects of BDNF deficiency on LPS- and nigericin-induced NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in vivo, and to elucidate the involvement of NF-kappa B signaling, autophagy, and ESCRT-III-dependent plasma membrane repair in this process. Materials and Methods: In this in vivo study, male Bdnf +/+ and Bdnf +/- mice were subjected to lipopolysaccharide (LPS) plus nigericin-induced NLRP3 inflammasome activation. Serum and hippocampus, cortex, liver, epididymal adipose, and muscle tissues were collected 24 h after stimulation for analysis of inflammasome-related, autophagy-related, and membrane repair-related proteins by Western blotting and of serum BDNF, interleukin-1 beta (IL-1 beta), and interleukin-18 (IL-18) by ELISA. Results: Bdnf +/- mice displayed significantly reduced circulating BDNF levels and exhibited exaggerated LPS plus nigericin-induced increases in IL-1 beta and IL-18 compared with Bdnf +/+ mice. Across all tissues, BDNF deficiency enhanced NF-kappa B p65, NLRP3, active caspase-1 p20, and GSDMD expression, indicating amplified inflammasome activation and pyroptosis. Conversely, LC3B and SQSTM1/p62 levels were decreased, and VPS4A expression, a key component of the ESCRT-III membrane repair machinery, was suppressed in Bdnf +/- mice, suggesting impaired selective autophagy, autophagosome formation, and plasma membrane repair. Conclusions: Together, these findings indicate that BDNF restrains NLRP3 inflammasome activation and GSDMD-mediated pyroptosis through inhibition of NF-kappa B signaling and coordinated activation of autophagy and ESCRT-III-dependent membrane repair. BDNF thus emerges as an endogenous negative regulator of inflammasome activity and a potential therapeutic target for conditions characterized by aberrant NLRP3-driven inflammation.Öğe Can serum interleukin 34 levels be used as an indicator for the prediction and prognosis of COVID-19?(Public Library Science, 2024) Karahan, Dogu; Bolayir, Hasan Ata; Bolayir, Asli; Demir, Bilgehan; Otlu, Onder; Erdem, MehmetObjective Interleukin 34 (IL-34) is a molecule whose expression is increased in conditions such as autoimmune disorders, inflammation, and infections. Our study aims to determine the role of IL-34 in the diagnosis, follow-up, and prognosis of Coronavirus Disease-19 (COVID-19).Method A total of 80 cases were included in the study as 40 COVID-19 positive patient groups and 40 COVID-19 negative control groups. The COVID-19-positive group consisted of 20 intensive-care unit (ICU) patients and 20 outpatients. Serum IL-34, c-reactive protein (CRP), ferritin, D-dimer, troponin I, hemogram, and biochemical parameters of the cases were studied and compared between groups.Results IL-34 levels were significantly higher in the COVID-19-positive group than in the negative group. IL-34 levels increased in correlation with CRP in predicting the diagnosis of COVID-19. IL-34 levels higher than 31.75 pg/m predicted a diagnosis of COVID-19. IL-34 levels did not differ between the outpatient and ICU groups in COVID-19-positive patients. IL-34 levels were also not different between those with and without lung involvement.Conclusion While IL-34 levels increased in COVID-19-positive patients and were successful in predicting the diagnosis of COVID-19, it was not found to be significant in determining lung involvement, risk of intensive care hospitalization, and prognosis. The role of IL-34 in COVID-19 deserves further evaluation.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 Could ELABELA be a Protective Biomarker in Patients with Abnormal Uterine Bleeding?(2024) KIRAN, TUGBA RAIKA; Doğan, Ümran Karabulut; Otlu, Önder; yildirim, engin; Erdem, Mehmet; İnceoğlu, FeyzaAim: Abnormal uterine bleeding (AUB) is a health problem characterized by various symptoms such as heavy and prolonged menstrual bleeding, affecting approximately 30% of female patients both physiologically and psychologically. The objective of this study was to assess serum Elabela (ELA) concentrations in women aged 18 and above diagnosed with functional AUB, and to compare these concentrations with those of healthy women. Material and Method: This prospective case-control study was performed from August 18, 2022 to December 30, 2022. This was a cross-sectional study including 50 women who applied to the gynecology service of Malatya Turgut Özal Training and Research Hospital with complaints of AUB and 50 women without AUB who underwent gynecological examination. The presence of AUB in patients was determined based on clinical examination conducted by a gynecologist and medical records. Demographic and clinical characteristics were recorded. Serum ELA levels were determined by commercial ELISA kit. Results: Serum ELA levels was significantly lower in patients with AUB (581.54±272.25 pg/mL) compared to the healthy group (744.55±300.31 pg/mL, p=0.005). In this study, ELA in patients with AUB showed 98% sensitivity and 80% specificity with a cut off value of 411.41 pg/mL (area under the curve [AUC], 68.1%; p=0.002). Conclusion: Serum ELA levels in patients with AUB were significantly lower than in healthy women. These results show that ELA is a good predictor of the pathophysiological process of AUB.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 Dual role of Kisspeptin-10 in modulating neuroinflammation: Downregulation of NLRP3 inflammasome activation and Caspase-1-mediated pyroptosis, and activation of BAG3-dependent aggrephagy in microglial cells(Elsevier, 2026) Kalkan, Omer Faruk; Erdem, Seniz; Erdem, Mehmet; Kalkan, Satinur Ateser; Sahin, Zafer; Uzun, Ali Yavuz; Karahan, Suleyman CanerBackground: Microglial NLRP3 inflammasome activation plays a central role in the neuroinflammatory cascade that contributes to the pathogenesis of various neurodegenerative diseases. Activation of the canonical inflammasome pathway leads to caspase-1 activation, gasdermin D (GSDMD) cleavage, and pyroptotic cell death, along with the release of pro-inflammatory cytokines such as interleukin-1(3 (IL-1(3) and interleukin-18 (IL-18). Kisspeptin-10 (KP-10), a bioactive neuropeptide of the kisspeptin family, has been shown to exert regulatory effects on immune function; however, its role in neuroinflammation process remains unclear. In this study, we investigated the effects of KP-10 on LPS + ATP-induced NLRP3 inflammasome activation and pyroptotic signaling in murine microglial cells. Results: KP-10 treatment significantly reduced NLRP3 expression, inhibited cleavage of caspase-1 into its active p20 subunit, and decreased GSDMD cleavage into its pore-forming N-terminal fragment (GSDMD-N), indicating suppression of inflammasome-dependent pyroptosis. KP-10 also attenuated the secretion of IL-1(3 and IL-18, confirming functional inhibition of the inflammasome pathway. Mechanistically, KP-10 markedly upregulated Bcl-2-associated athanogene 3 (BAG3), a key co-chaperone involved in selective autophagy. Conclusion: These findings demonstrate that KP-10 suppresses microglial pyroptosis and neuroinflammatory signaling through dual mechanisms: inhibition of the NLRP3-caspase-1-GSDMD axis and activation of BAG3-dependent selective autophagy. This study identifies KP-10 as a novel modulator of microglial inflammasome activity and highlights its therapeutic potential for treating neuroinflammatory and neurodegenerative disorders.Öğe Effect of Altered Iron Metabolism on Hyperinflammation and Coagulopathy in Patients with Critical COVID-19: A Retrospective Study(2022) Otlu, Önder; Erdem, Mehmet; Korkmaz, Kübranur; Günay, Özge Ota; İn, Erdal; Kıran, Tuğba Raika; Bay Karabulut, AysunAbstract: A novel coronavirus disease 2019 (COVID-19) outbreak has started in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The relationship between altered iron homeostasis and hyperinflammation may be hallmarks of COVID-19 disease. We aimed to compare some iron (ferritin and iron), inflammation (C-reactive protein [CRP], hemoglobin, lactate dehydrogenase [LDH], neutrophil) and coagulation (prothrombin time [PT], activated partial thromboplastin time [APTT], D-dimer, platelet) marker results of critical COVID-19 patients with healthy controls results. In this single center retrospective study, 50 critical patients diagnosed with COVID-19 were included, demographic, clinical characteristics, severity of disease and laboratory test results were elicited from electronic medical records and compared to 50 healthy people. A statistically significant increase in CRP, LDH, neutrophil, PT, APTT, D-dimer ferritin levels was observed in critical COVID-19 patients compared with healthy people while a statistically significant decrease was observed in hemoglobin and iron levels. In addition, no statistically significant change in platelet levels was observed. Ferroptosis may be a significant cause of multiple organ failure in critical COVID-19 patients. Ferroptosis inhibitors might have potential to combat ferroptosis in COVID-19. Therefore, larger studies are needed to ferroptosis in COVID-19 in vivo and in vitro.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 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 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 Proprotein convertase subtilisin/kexin type 9 and apelin in fibromyalgia syndrome(2024) TAŞ, NEVSUN PIHTILI; Baykara, Rabia Aydogan; KAMANLI, Ayhan; Gürbüz, Ali; CÜRE, Erkan; cure, medine cumhur; Erdem, MehmetObjectives: This study aimed to investigate the potential roles of proprotein convertase subtilisin/ kexin type 9 (PCSK9) and apelin in the etiology of fibromyalgia syndrome (FS). Patients and methods: The retrospective study was conducted between May 2022 and February 2023. Fifty-eight female FS patients (mean age: 45.2±9.9 years; range, 25 to 66 years) and 30 age- and body mass index-matched control subjects (mean age: 43.1±9.9 years; range, 26 to 67 years) were included in the study. Apelin and PCSK9 levels of all individuals were measured using appropriate methods. Results: The levels of PCSK9 (173.2±62.2 vs. 75.1±44.1, p<0.001) and apelin (354.6±195.5 vs. 229.0±83.2, p<0.001) were significantly higher in patients with FS compared to the control group. A positive correlation was found between PCSK9 and apelin levels and various measures, including the Fibromyalgia Impact Questionnaire (FIQ), Symptom Severity Scale (SSS), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Inventory (BDI). Additionally, there was a positive correlation between apelin levels and FIQ, SSS, PSQI, Beck Anxiety Inventory, and BDI scores. The optimal cutoff value for PCSK9 in predicting FS was 110.0 ng/mL, with a sensitivity of 84.5% and specificity of 83.9% (area under the curve [AUC]=0.920, 95% confidence interval [CI]: 0.852-0.987, p<0.001). For apelin, the optimal cutoff value for predicting FS was 258.8 ng/L, with a sensitivity of 63.8% and specificity of 64.5% (AUC=0.732, 95% CI: 0.623–0.840, p<0.001). Conclusion: Our findings suggest that PCSK9 may play a role in FS etiology and potentially contribute to oxidative stress. Increased apelin levels may be a compensatory response to high oxidative stress, possibly leading to hyperalgesia. Both PCSK9 and apelin can be predictive markers for FS.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 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 brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone mitigates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis and enhances the negative regulatory pathways of pyroptosis in microglia(Elsevier, 2025) Erdem, Mehmet; Erdem, Seniz; Karahan, Suleyman Caner; Alver, Ahmet; Karabulut, Soner; Yildiz, GokhanMicroglia are resident immune cells of brain, which serves as a driver of the innate immunity within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that is critical component of the innate immunity and hyperactivation of inflammasome under various conditions contributing to the pathogenesis of neurodegenerative diseases (NDs). 7,8-Dihydroxyflavone (7,8-DHF) have become the focus of attention in studies on NDs due to exert its neurotrophic effects in the CNS. Recent studies have shown encouraging outcomes targeting immune regulatory and neuroprotective properties. 7,8-DHF is a specific tropomyosin-related kinase receptor B (TrkB) agonist and bioavailable brainderived neurotrophic factor (BDNF) mimetic, which has immunomodulator properties in the CNS. In the present study, we researched the effects of BDNF mimetic 7,8-DHF on NLRP3 inflammasome activation, GSDMDmediated pyroptosis, NF-kappa B signaling, ESCRT-III-dependent plasma membrane repair, and selective autophagy in LPS plus ATP-induced murine N9 microglial cells. These findings demonstrated that BDNF mimetic 7,8-DHF significantly reduced NLRP3 inflammasome activation, decreased active caspase-1 the levels, inhibited secretion of proinflammatory cytokine IL-1 beta and IL-18 levels through the I kappa B alpha/NF-kappa B axis. Furthermore, we showed that BDNF mimetic 7,8-DHF activated selective autophagy and ESCRT-III-dependent plasma membrane repair, both of which play crucial roles in the negative regulation of NLRP3 inflammasome activation. Our study reveals that BDNF mimetic 7,8-DHF effectively prevents microglial NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by inhibiting I kappa B alpha/NF-kappa B, promoting ESCRT-III-dependent plasma membrane repair and enhancing selective autophagy.
