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    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, Feyza
    Background 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.
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    Combined preoperative thyroglobulin and ACR-TIRADS assessment: implications for fine-needle aspiration biopsy strategy and thyroid cancer diagnosis
    (Cukurova Univ, Fac Medicine, 2026) Karahan, Dogu; Keskin, Lezan; Mete, Burak
    Purpose: The aim of this study is to evaluate the relationship of Thyroglobulin (Tg) with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) and Bethesda and its correlation with malignancy. Materials and Methods: The study included 603 cases. Ultrasonography (US), fine needle aspiration biopsy (FNAB), Tg and anti-Tg results were evaluated retrospectively. Nodules were scored according to the ACR-TIRADS. FNAB results were evaluated according to the Bethesda. The relationship between Tg levels, ACR-TIRADS, and FNAB results was evaluated to determine the risk of thyroid malignancy. Results: The mean age of cases was 50.98 +/- 13.73 (min-max: 18-79). 85.1% of the patients were female. Tg was statistically significantly higher in malignant patients (Bethesda 6). In the ROC analysis, the optimum cut-off value for Tg in predicting malignancy was found to be 245 ng/dL. Mean Tg levels were statistically significantly higher in the TIRADS 4, 5 groups than in the TIRADS 2 and 3 groups. Conclusion: Results showed that Tg is elevated in thyroid nodular disease, especially in malignant nodules. The Tg levels increased in parallel with the ACR-TIRADS malignancy-risk score. If these results are supported by other studies, the evaluation of Tg together with ACR-TIRADS may make an additional contribution to the FNAB decision and the prediction of thyroid malignancies.
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    Dietary Antioxidant Capacity, Inflammation, and Insulin Resistance in Women with Polycystic Ovary Syndrome: An Integrated Metabolic and Nutritional Assessment
    (Dove Medical Press Ltd, 2026) Alatas, Hacer; Arslan, Nurgul; Keskin, Lezan; Agrali, Cansu
    Background: Polycystic ovary syndrome (PCOS) is characterized by metabolic dysfunction, low-grade inflammation, and oxidative stress. However, the role of dietary antioxidant capacity in shaping inflammatory and metabolic outcomes remains insufficiently explored. Objective: To evaluate dietary antioxidant capacity and its associations with inflammation and insulin resistance among women with PCOS compared with healthy controls. Methods: A cross-sectional study was conducted with 129 women with PCOS and 135 age-matched controls. Dietary antioxidant capacity was assessed through a composite antioxidant score. Anthropometric indices, inflammatory markers (WBC, neutrophils, NLR), and metabolic parameters (fasting glucose, insulin, HOMA-IR) were compared. Structural equation modeling (SEM) and hierarchical regression were used to test direct and indirect pathways linking diet, inflammation, and insulin resistance. Results: Women with PCOS had significantly lower total dietary antioxidant scores than controls (11.8 vs. 14.3). Inflammatory status was higher, with NLR values elevated in the PCOS group (2.09 vs. 1.63). Insulin resistance showed the largest difference: HOMA-IR levels were nearly twice as high in women with PCOS (3.52 vs. 1.98). Structural equation modeling indicated that higher antioxidant intake reduced insulin resistance both directly ((3 = -0.21) and indirectly by lowering inflammation ((3 = -0.13). Regression analyses confirmed that PCOS status, higher inflammation, and lower antioxidant intake independently predicted increased HOMA-IR. Conclusion: Reduced antioxidant intake is strongly linked with heightened inflammation and impaired insulin sensitivity in women with PCOS. Enhancing antioxidant-rich dietary patterns may offer a promising nutritional strategy to mitigate metabolic and inflammatory disturbances in PCOS.
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    Effect of fine needle aspiration biopsy on change in thyroid nodule elasticity
    (Societatea Romana de Ultrasonografie in Medicina si Biologie, 2026) Akçicek, Mehmet; Dağ, Nurullah; Keskin, Lezan; Petik, Bülent; Ünlü, Serkan
    Aims: This study aimed to investigate changes in the stiffness of thyroid nodules following fine needle aspiration biopsy (FNAB), using shear wave elastography (SWE), a non-invasive imaging technique utilized in thyroid nodule evaluation. Material and Methods: A total of 82 patients scheduled to undergo FNAB for the first time were included. Ultrasound and SWE examinations were performed before the procedure and again 8 to 10 weeks after FNAB. Nodule stiffness was measured in kilopascals (kPa) during both evaluations, and changes in elasticity were assessed. Results: The mean SWE stiffness of the nodules significantly decreased from 21.80 ±11.43 kPa before FNAB to 17.83 ±9.98 kPa after FNAB (p = 0.001). Smoking status and serum free T3 levels were significantly associated with changes in SWE stiffness (p < 0.05). However, no significant difference was observed between TIRADS 3 and TIRADS 4 categories regarding the change in stiffness (p = 0.223). Conclusion: This study demonstrates a significant reduction in thyroid nodule stiffness after FNAB as measured by SWE. These post-biopsy changes may lead to potential misinterpretations in subsequent elastographic evaluations, possibly affecting diagnostic accuracy and clinical decision-making. © 2026, Societatea Romana de Ultrasonografie in Medicina si Biologie, All rights reserved.
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    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, Feyza
    Metabolic 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.
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    Unveiling the significance of Netrin-1 and Netrin-4 in metabolic syndrome
    (Nature Portfolio, 2026) Kiran, Tugba Raika; Ayyildiz, Gamze; Keskin, Lezan; Erdem, Mehmet
    Metabolic 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.