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Biomarkers of immune hyperactivation and inflammation are elevated in pregnancies complicated by fetal Trisomy-21
(Taylor & Francis Ltd, 2025) Turkcuoglu, Ilgin; Sinaci, Selcan; Melekoglu, Rauf; Unuvar, Songul; Celik, Nesibe Zeyveli; Yasar, Seyma; Polat, Busra Berfin
Objective To compare interferon-linked/inflammatory biomarkers (neopterin, indoleamine-2,3-dioxygenase [IDO], and YKL-40) in maternal serum and amniotic fluid between Trisomy-21 and chromosomally normal pregnancies. Methods This prospective case-control study included pregnancies diagnosed with Trisomy-21 and chromosomally normal pregnancies as controls. Neopterin, IDO, and YKL-40 levels in maternal serum and amniotic fluid samples were measured using ELISA. Results Neopterin and YKL-40 levels were significantly higher in amniotic fluid (p < 0.05) and maternal serum (p < 0.05), respectively, in the Trisomy-21 group. Maternal serum IDO showed a trend toward increase in Trisomy-21 pregnancies, while amniotic fluid levels did not differ between groups. All measurements were above assay detection limits. Conclusion Trisomy-21 pregnancies showed elevated AF neopterin and elevated MS YKL-40, while IDO was not significantly different. This pattern is compatible with differences in interferon-linked inflammatory/vascular pathways in Trisomy-21 pregnancies, but does not establish a mechanism. Further studies are needed to validate these findings.
CLINICAL SIGNIFICANCE OF INCREASED SERUM NEOPTERIN IN CHRONIC KIDNEY FAILURE AS A BIOMARKER OF CELL-MEDIATED IMMUNITY
(Sciendo, 2019) Unuvar, Songul; Aslanhan, Hamza
Background: Neopterin is a pyrazino-pyrimidine compound which is used as a marker of cell-mediated immunity in a variety of diseases. It is known that neopterin levels increase in diseases where interferon-gamma (IFN-gamma) stimulation is present, and also as a result of deficiencies in renal function, given that the primary means of elimination of neopterin is through the kidneys. In this study, we aimed to investigate the role of increased neopterin levels as a prognostic biomarker in patients with impaired renal function. Methods: A total of 90 individuals including 63 patients with chronic kidney failure (CKF) and 27 healthy volunteers were included in the study. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay. A Mann-Whitney U test and a Pearson Correlation Test were used in the statistical analysis, with a p value of <0.05 being considered statistically significant. Results: The mean age was 52.21 +/- 0.16 years in the patient group and 56.55 +/- 0.32 years in the control group. In the CKF patients, serum neopterin levels increased to a significantly greater degree than in the control group (p<0.001), while no statistically significant correlation was identified between serum neopterin levels and age (p>0.05). Conclusions: A significant increase was found in the serum neopterin levels in the CKF patients, due to both the triggering of the disease and the reduction of neopterin elimination.
Combination of 2 Bioactive Compounds for Treatment of Breast Cancer: Triterpenoid Cucurbitacin I and Phenolic CAPE
(Sage Publications Inc, 2019) Karakus, Fuat; Yilmaz, Kadir; Eyol, Ergul; Unuvar, Songul
It has been demonstrated that both cucurbitacin I (Cu I) and caffeic acid phenethyl ester (CAPE) have anticancer activities. The current study aimed to examine the proliferation, migration, and colony formation actions of Cu I and CAPE on MCF-7 and MDA-MB-231 human breast cancer cells. The antimigration, antiproliferative, and colony inhibition effects of different dosages of Cu I, CAPE, and Cu I + CAPE on cells were determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell viability assay, wound healing, and colony formation assays, respectively. Compared with single treatment, combination of 2 bioactive compounds enhanced the anticancer activity. When Cu I and CAPE were combined, a strong inhibitor effect was shown on cell growth, colony formation, and cell migration compared with the compounds used singly. The concomitant treatment with Cu I and CAPE showed stronger antiproliferative activities on both MCF-7 and MDA-MB-231 cells compared with individual treatment with either Cu I or CAPE. Caffeic acid phenethyl ester is a specific inhibitor of Nuclear factor-kappa B (NF-kappa B). It shows anticancer activity depending on this inhibition. It is a bioactive phenolic compound that is derived from propolis. Cucurbitacin I is a selective Januskinase/signal transducer and a transcription-3 signal pathway inhibitor. Combination of these 2 natural anticancer compounds is beneficial in the treatment of cancer, as well as the side effects associated with classical chemotherapeutics not being observed with the use of these compounds.
Comparison of preoperative serum neopterin, periostin, indoleamine 2,3-dioxygenase, YKL-40, and tenascin-C levels with current tumor markers for early-stage endometrial cancer
(Wiley, 2021) Unuvar, Songul; Melekoglu, Rauf; Turkmen, Nese B.; Yilmaz, Ercan; Yasar, Seyma; Yuce, Hande
Objective: To compare the predictive value of serum levels of neopterin, periostin, YKL-40, tenascin-C (TNC), and indoleamine 2,3-dioxygenase (IDO) with current tumor markers for the primary diagnosis of early-stage endometrial cancer. Methods: A prospective cross-sectional study was conducted between January 2020 and November 2020. A total of 59 patients (38 women newly diagnosed with early-stage endometrial cancer [study group] and 21 women with benign endometrial pathologies [control group]) were enrolled. Blood samples were collected prior to surgery and underwent immunoassay analysis. Results: Carcinoembryonic antigen (CEA), periostin, and IDO levels were significantly higher in the study group than the control group (P = 0.008, P = 0.034, and P = 0.003, respectively). Receiver operating characteristic curve analysis revealed that IDO, periostin, and CEA were good predictors of early-stage endometrial cancer (AUC = 0.733, 95% CI, 0.602-0.840, P < 0.002; AUC = 0.668, 95% CI, 0.533-0.785, P = 0.018; and AUC = 0.709, 95% CI, 0.576-0.820, P = 0.002, respectively). Correlation analysis revealed no significant correlation of any biomarker with age or body mass index in either the control or study group. Conclusion: Serum CEA, periostin, and IDO levels were significantly higher in women with endometrial cancer than in those without cancer. These results may help identify new markers for diagnosing endometrial cancer.
Current Pandemic in the World: Monkeypox from Past to Present
(Acad Brasileira De Ciencias, 2023) Sahin, Yasemin; Yuce, Hande; Unuvar, Songul; Ciftci, Osman
Monkeypox is a zoonotic viral infection that was first identified in humans in 1970 in the Democratic Republic of Congo. The cases seen again in early May 2022 have reached 78.000 as of today. On July 23, 2022, the World Health Organization decided that the monkeypox outbreak represents a public health emergency. For the early diagnosis and effective treatment of monkeypox, inter-individual transmission routes, disease symptoms, factors affecting the course of the disease, presence of another infection, prognosis, pharmacological agents used in the prophylactic treatment, and their effects, populations at risk, waste disposal protocol should be known. For this reason, our aim is to reveal the sources of transmission of the monkeypox virus from past to present, what are the signs and symptoms in patients after infection, ways of protection from the virus, the mutation status of the virus, and treatment approaches.
Cytotoxic Effects of Cucurbitacin I and Ecballium elaterium on Breast Cancer Cells
(Natural Products Inc, 2018) Yilmaz, Kadir; Karakus, Fuat; Eyol, Ergul; Tosun, Emir; Yilmaz, Ismet; Unuvar, Songul
The objective of this study was to investigate the inhibitory effect of cucurbitacin I (CuI) and Ecballium elaterium L. (fruit juice and chloroform extract) on breast cancer cells (MCF-7 and MDA-MB-231). The Cul content of E. elaterium fruit juice and chloroform extract was quantified using high performance liquid chromatography. The cytotoxic effects of the fruit juice, chloroform extract and CuI were determined by MTT, wound healing and colony formation assays; all had an anti-proliferative activity on the breast cancer cells. Clarifying the mechanisms of cucurbitacins will enable the identification of new molecular targets for breast cancer therapy.
Determination of Element Concentrations in Commercial Infant Formulas Using Atomic Absorption Spectrometry
(Atomic Spectroscopy Press Ltd, 2017) Unuvar, Songul; Savan, Ebru Kuyumcu; Karaaslan, Nagihan M.
The presence of heavy metals, inadequate minerals and elements in infant foods is of great concern. In this study, the heavy metals aluminum (Al) and lead (Pb), essential elements such as iron (Fe) and zinc (Zn), and minerals such as calcium (Ca), potassium (K), magnesium (Mg), and sodium (Na) were determined by atomic absorption spectrometry (AAS) in five different brands of 20 infant formula samples obtained from pharmacies and supermarkets in Malatya, Turkey. The Joint FAO/WHO Expert Committee on Food Additives GECFA) has set the maximum concentration levels of heavy metals in infant formula and levels of provisional tolerable weekly intake (PTWI) of these metals by infants. The levels of Al and Pb in the analyzed samples were found to be under legal limits. The recommended daily intake (RDI) of the essential elements and minerals were found within normal and permissible ranges, showing that the formulas are safe for infants.
Diagnostic utility of lipocalin 2 and metalloproteinase 9 levels in early-stage endometrial cancer
(Sage Publications Inc, 2024) Unuvar, Songul; Melekoglu, Rauf; Yuce, Hande; Celik, Nesibe Zeyveli; Okumus, Ezgi Bulut; Toprak, Serhat; Tanbek, Kevser
Background Endometrial cancer (EC) is the fourth most common gynecologic malignancy among women. Histopathologic examination is considered gold-standard for diagnosis of EC. However, these examinations sometimes not be useful in distinguishing early stage types of EC. Object & imath;ves The current study aimed to investigate the clinicopathological significance of Lipocalin-2 (LCN2), matrix metalloproteinase-9 (MMP9), and ferritin in tumor progression. Methods A total of 98 patients (55 women newly diagnosed with early-stage endometrial cancer [study group] and 43 women with benign endometrial pathologies [control group]) were enrolled. Results There was a significant difference between diagnosis (p < 0.001), surgical procedure (p < 0.001), pathology (p = 0.002), stage (p < 0.001), lymphovascular invasion (LVI) (p = 0.002), myometrial invasion (p < 0.001), and staining intensity (p < 0.001), MMP9 (p = 0.023), LCN2 (p < 0.001), glucocorticoid (GC) (p = 0.048), tumor necrosis factor-alpha (TNF-alpha) (p = 0.044), menopause duration (p = 0.001), body weight (p < 0.001), and body mass index (BMI) (p < 0.001) were found to be higher, and ferritin levels (p = 0.047) were lower in the endometrial adenocarcinoma group compared to the benign endometrial pathologies. Conclus & imath;on LCN2, MMP9, and ferritin are practical markers in early cases of endometrial cancer. Serum LCN2 and MMP9 levels may be good clinical tools for the auxiliary diagnosis of early-stage endometrial cancer. Ferritin was also significantly sensitive. Therefore, detecting these markers together may be more beneficial for cancer diagnosis.
Evaluation of Common Non-pharmacological Chemical Substance Poisonings in Childhood
(Galenos Yayincilik, 2017) Unuvar, Songul
Acute intoxications in adolescents and adults are mostly associated with intentional or accidental ingestions. Intoxications are commonly seen in children aged between 1 and 5 years and most of the cases are associated with accidental intake. In most of the children, no clinical symptoms related to intoxication are observed or only mild effects can develop. The main route of drug elimination is through kidneys. Absolute clearance in children is often lower than in adults but weight-adjusted clearance is higher. Depending on more rapid elimination in children the plasma half-life of the drug might be shorter in children than in adults. A shorter elimination half-life means that plasma steady-state is achieved with repeated doses. It is important to prevent childhood intoxications, and the use of child-resistant packaging and adequate supervision together with the secure storage of household substances are the basis of prevention of accidental childhood intoxications. Intoxications represent one of the most common medical emergencies in children, and epidemiological characteristics vary in different countries. Therefore, special epidemiological surveillance is necessary for each country to determine the problem according to which preventive measures should be taken. Early awareness and taking appropriate therapeutic measures seems to be effective in the reduction of mortality rate. The major and most common non-pharmacological chemical intoxications in childhood have been reviewed here with the intent of helping health-care professionals, particularly pediatricians to recognize and reduce the risk of harmful childhood intoxications.
Evaluation of Lipocalin-2 and Metalloproteinase-9 Gene Expressions in Early-Stage Endometrial Cancer
(Wiley, 2023) Unuvar, Songul; Melekoglu, Rauf; Bulut, Ezgi; Dogan, Aysegul; Turkmen, Nese Basak; Yuce, Hande; Yilmaz, Ercan
[Abstract Not Available]
Evaluation of NMR Results of Newly Synthesized Platinum-Based N- Heterocyclic Carbene Complexes
(Wiley, 2023) Aslan, Sumeyye; Yuce, Hande; Yasar, Sedat; Bugday, Nesrin; Turkmen, Nese Basak; Eke, Benay Can; Unuvar, Songul
[Abstract Not Available]
Evaluation of serum neopterin, periostin, Tenascin-C, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-2 levels in obese pregnant women
(Galenos Publ House, 2022) Melekoglu, Rauf; Unuvar, Songul; Turkmen, Nese Basak; Cetin, Asli; Celik, Nesibe Zeyveli; Yuce, Hande; Yasar, Seyma
Objective: To investigate the role of extracellular matrix proteins in the molecular mechanism of inflammatory response in obese pregnant women by comparing serum levels of neopterin, periostin, Tenascin-C, tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-2 between obese and normal weight pregnant women in the third trimester. Materials and Methods: A prospective cross-sectional study was conducted between April 2021 and December 2021. A total of 84 pregnant women were included and three groups were formed with 28 participants in each group. Results: Serum levels of neopterin, periostin, Tenascin-C and tissue inhibitor of metalloproteinase-1 were significantly higher in class II-III obese pregnant women than in class I obese and normal-weight women (p=0.002, p<0.001, p<0.001, and p<0.001, respectively). There was no significant difference in serum matrix metalloproteinase-2 levels between the groups (p=0.769). Receiver operating characteristic curve analysis showed that Tenascin-C and periostin were effective in predicting pre-eclampsia [area under the curve (AUC)=0.82, 95% confidence interval (CI), 0.72-0.90, p<0.001 and AUC=0.71, 95% CI, 0.60-0.80, p=0.007, respectively]. Conclusion: This study demonstrated that class II-III obese pregnant women had significantly higher serum levels of neopterin, periostin, Tenascin-C, and tissue inhibitor of metalloproteinase-1 in the third trimester. These higher serum levels may be associated with the adverse perinatal effects of obesity during pregnancy.
Evaluation of the Cytotoxic Activity of Citrinin on Human Prostate Cancer Cell Lines
(Wiley, 2025) Yuce, Hande; Ozek, Dilan Askin; Unuvar, Songul
[No abstract available]
Evaluation of the Relationship Between Serum Metallothionein and Trace Element Levels in Multiple Sclerosis Patients
(Wiley, 2023) Yuce, Hande; Tecellioglu, Mehmet; Tanbek, Kevser; Yasar, Seyma; Turkmen, Nese Basak; Ates, Ilker; Unuvar, Songul
[Abstract Not Available]
Impact of patulin on apoptosis, autophagy, and tumor growth in human malignant mesothelioma and normal mesothelial cells
(Biomedpress, 2025) Akkutlu, Rumeysa; Yuce, Hande; Ozek, Dilan Askin; Berberoglu, Yasemin; Unuvar, Songul
Patulin (PAT) is a mycotoxin produced by certain molds, particularly species of the genera Aspergillus and Penicillium. It is found predominantly in apple-derived products and is associated with both acute and chronic toxicities. Although comprehensive data on the anti-cancer properties of PAT are presently lacking, preliminary evidence suggests that it can influence cancer cells by enhancing cellular apoptosis and inducing cytotoxicity. To evaluate the potential of PAT as a therapeutic approach for malignant mesothelioma, we investigated its effects on the malignant mesothelioma cell line H2452 and the non-malignant mesothelial cell line MeT-5A. Cells were exposed to PAT (1-200 mu M). Cell viability was assessed using the MTS assay, and cell migration was evaluated using the wound-healing assay. Expression levels of genes related to autophagy and apoptosis (SQSTM1, Beclin-1, Atg5, Atg7, Bax, Bcl-2) were measured using RT-PCR. PAT produced a dose-dependent decrease in cell viability and exhibited greater cytotoxicity toward mesothelioma cells than toward healthy cells. The wound-healing assay demonstrated that PAT impeded cellular migration, as evidenced by dysregulated wound closure. In cancer cells, PAT down-regulated Bax, Bcl-2, Beclin-1, and SQSTM1, while up-regulating Atg5 and Atg7. In healthy cells, it reduced Bax, Bcl-2, Beclin-1, SQSTM1, and Atg7, and elevated Atg5. It increased apoptosis in both healthy and cancer cells while modulating autophagy pathways in both cell types, potentially attenuating autophagy in cancer cells and disrupting this process in healthy cells. Our findings indicate that PAT may significantly restrict tumor progression in human mesothelial cancer models.
In vitro effect of carbonic anhydrase inhibitor acetazolamide on cell viability, migration and colony formation of colorectal cancer cells
(Springer, 2018) Karakus, Fuat; Eyol, Ergul; Yilmaz, Kadir; Unuvar, Songul
Acidification of extracellular medium in malignant tumors increases the invasive behaviors of cancer cells. In normal healthy tissues, acid production is catalyzed by carbonic anhydrases. Some of the carbonic anhydrase enzymes are overexpressed in certain types of cancer. The present study aimed to investigate the effect of acetazolamide, a potent carbonic anhydrase inhibitor, on in vitro cultivated cancer cells. Three different assays (MTT test, wound healing and clonogenic assay) were performed using human colorectal adenocarcinoma cells (SW620) to evaluate the suppressive effect of acetazolamide, on the colorectal cancer cells migration ability, colony formation and cell viability. The dose-dependent (1-1000 mu M) reducing effect of acetazolamide on the cell viability was more significant within the first 48 h. This inhibitory effect of acetazolamide was found to be decreased at 72 h, and affects cells migration ability of cells at 24 and 48 h. Acetazolamide was observed to inhibit the cell viability, migration and colony formation ability of cells, depending on dose.
Inhibition of cell proliferation, migration and colony formation of LS174T Cells by carbonic anhydrase inhibitor
(Makerere Univ, Fac Med, 2018) Karakus, Fuat; Eyol, Ergul; Yilmaz, Kadir; Unuvar, Songul
Background: Metastasis is the leading cause of cancer deaths. Migration of tumor cells is an important stage in metastasis. Therefore, recent studies have focused on clarifying migration and migration-dependent cell functions such as angiogenesis, wound healing, and invasion. Objectives: In the present study, we aimed to investigate the effect of acetazolamide, which is a classical carbonic anhydrase inhibitor, on the cell viability, migration, and colony forming capacity of human LS174T colorectal cancer cells. Methods: Three different cell culture techniques (MTT test, wound healing and clonogenic assay) were performed in this in vitro study on colorectal cancer cells. Results: Acetazolamide reduced the cell viability, migration and colony formation ability of cells depending on dose. There was no significant difference between the cells treated with acetazolamide with 1 mu M dose and the control. However, it can be concluded that acetazolamide exerts its effect on human colorectal cancer cells at 10-1000 mu M concentrations. Conclusion: Acetazolamide was observed to significantly inhibit the cell viability, colony forming capacity, and migration ability in the culture medium of LS174T cells. This inhibitor effect of acetazolamide was observed to be dependent on the concentration in medium.
Mercury exposure, neopterin profile, and tryptophan degradation in dental technicians
(De Gruyter Poland Sp Z O O, 2022) Girgin, Gozde; Palabiyik-Yucelik, Saziye Sezin; Sipahi, Hande; Kilicarslan, Bilge; Unuvar, Songul; Tutkun, Engin; Yilmaz, Omer Hinc
Amalgam has been widely used as a restorative dental material for over 150 years. Most standard dental amalgam formulations contain approximately 50% elemental mercury in a mixture of copper, tin, silver, and zinc. Mercury is a highly volatile metal, which can easily vaporize to a colorless and odorless gas. It has been demonstrated that mercury is released from dental amalgam, which is increased by chewing, eating, brushing, and drinking hot liquids. Besides this, amalgam is the main occupational exposure source of mercury for dental workers. It is known that mercury exposure causes immune modulation in humans. In this study, it was aimed to evaluate the changes in neopterin levels and tryptophan (Trp) degradation in dental technicians. It was observed that low levels of occupational mercury exposure resulted in decreased neopterin, kynurenine (Kyn), and Kyn/Trp levels. Moreover, mercury and neopterin levels had a significant positive correlation in workers. The lower neopterin levels and Kyn/Trp in dental technicians compared to an unexposed group indicates a possible immune suppression with low level of occupational mercury exposure during amalgam preparation. The relationship between urinary mercury levels as an indicator of occupational mercury exposure and neopterin reminded an effect on T-cell-mediated immune response.
Microbial Foodborne Diseases
(Academic Press Ltd-Elsevier Science Ltd, 2018) Unuvar, Songul
[Abstract Not Available]
NEOPTERIN AND RECURRENT SPONTANEOUS ABORTION (RSA): THE EFFECT OF CELLULAR IMMUNE SYSTEM ACTIVATION ON SUBSEQUENT PREGNANCY
(Central Bohemia Univ, 2017) Unuvar, Songul; Tanriverdi, Zubeyde
Background: Recurrent miscarriages are common complications in pregnancy. Neopterin is one of the immunologic biomarkers of several diseases related to activation of the cellular immune system. RSA is associated with immune system related abnormalities. Objectives: We aimed to investigate the effectiveness of neopterin levels in the early diagnosis of RSA. Methods: Eighty RSA patients and forty-three healthy controls were included in the study. The neopterin concentrations were determined by the enzyme-linked immunosorbent assay (ELISA) method. For the statistical analysis, Mann-Whitney U test and Pearson correlation test were used the; p<0.05 was considered statistically significant. Results: Serum mean neopterin levels were 16.47 +/- 0.095 nmol/L in RSA group and 6.14 +/- 0.041 nmol/L in control group, respectively. Compared to the control group, a statistically significant increase (p=0.0183) in the serum neopterin levels of the patients was observed. There was a negative correlation between serum neopterin level and age in both the control (R=0.0774, p=0.6236) and RSA groups (R=0.1415, p=0.2089). However, this correlation was not statistically significant (p>0.05). Conclusions: With overstimulation of interferon-gamma (INF-gamma) during pregnancy, the production of neopterin increases by monocytes/macrophages. The measurement of neopterin levels in the serum contributes to the early diagnosis of pregnancy losses.

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