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Öğe Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells(Wiley, 2023) Hacioglu, Ceyhan; Kar, Fatih; Davran, Fatih; Tuncer, CengizGlioblastoma (GBM) is classified as a stage-IV glioma. Unfortunately, there are currently no curative treatments for GBM. Poly(rC)-binding protein 1 (PCBP1) is a cytosolic iron chaperone with diverse functions. PCBP1 is also known to regulate autophagy, but the role of PCBP1 in ferroptosis, iron-dependent cell death pathway, remains unrevealed in GBM cells. Here, we investigated the effects of borax, a boron compound, on the ferroptosis signaling pathway mediated by PCBP1 and autophagy. The study analyzed cell viability, proliferation, and cell cycle on U87-MG and HMC3 cells to investigate the effects of borax. After determining the cytotoxic concentrations of borax, morphological analyzes and measurement of PCBP1, Beclin1, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPx4) and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were performed. Finally, expression levels of PCBP1, Beclin1, GPx4 and ACSL4, and caspase-3/7 activity were determined. We found that borax reduced U87-MG cell viability in a concentration- and time-dependent manner. Additionally, borax altered cell proliferation and remarkably reduced S phase in the U87-MG cells and exhibited selectivity by having an opposite effect on normal cells (HMC3). According to DAPI staining, borax caused nuclear deficits in U87-MG cells. The result showed that borax in U87-MG cells induced reduction of the PCBP1, GSH, and GPx4 and enhancement of Beclin1, MDA, and ACSL4. Furthermore, borax triggered apoptosis by activating caspase 3/7 in U87-MG cells. Our study indicated that the borax has potential as an anticancer treatment for GBM via regulating PCBP1/Beclin1/GPx4/ACSL4 signaling pathways.Öğe COVID-19 Enfeksiyonunda Ağırlaştırıcı Risk Faktörlerinin Araştırılması(2023) Yekenkurul, Dilek; Ince, Nevin; Yıldırım, Mustafa; Sungur, Mehmet Ali; Escan, Elif; Davran, Fatih; Altınsoy, Hasan BakiAmaç: Koronavirüs hastalığı-2019, yaklaşık iki yıl önce Çin'de başlayan ancak tüm dünyayı etkisi altına alan bir salgına neden olmuştur. Koronavirüs hastalığı-2019 enfeksiyonu ile takip edilen hastaların değerlendirilmesi, ciddi enfeksiyon için risk faktörlerinin ve göstergelerinin belirlenmesi amaçlanmıştır. Gereç ve Yöntemler: Koronavirüs hastalığı-2019 enfeksiyonu ile 15 Mart- 01 Haziran 2020 tarihleri arasında yatarak tedavi gören hastalar araştırıldı. Hastalar oksijen satürasyonlarına göre iki gruba ayrıldı; oksijen satürasyonu % 90'ın üzerinde olan hastalar grup 1, % 90 ve altı olan hastalar grup 2 olarak belirlendi. Bu iki grup ağırlaştırıcı risk faktörleri açısından karşılaştırıldı. Bulgular: Bu çalışmaya 90 hasta (46 kadın, 44 erkek) dahil edildi. Bilgisayarlı toraks tomografisinde orta-şiddetli pnömonik tutulum (p=0,002) ve yüksek ateş (pÖğe COVID-19 Hastalarının Kan Gruplarına Göre Hemogram Parametrelerinin Değerlendirilmesi(2022) Gamsızkan, Zerrin; Kaya, Abdulkadir; Tuncel, Mert Can; Işık, Abdullah; Davran, Fatih; Şahin, İdrisAmaç: COVID-19 hastalığı, tüm Dünyada birçok insanın hayatını tehdit ettiğiiçin hastaların laboratuar parametreleri her açıdan incelenmektedir. Kan grupları ve COVID-19 ilişkisi de birçok araştırmada tartışılmıştır. Çalışmamızın amacı, COVID-19 hastalarının kan gruplarına göre hemogram parametrelerini incelemektir. Gereç ve Yöntemler: Çalışmamız, retrospektif olarak tasarlanmış, tanımlayıcı-kesitsel bir çalışmadır. Çalışmada, 01.12.2020-01.02.2021 tarihleri arasında COVID-19 şüphesi ile acil pandemi polikliniğine başvuran hastalar kan grupları ve laboratuar tetkikleri ile değerlendirildi. Bulgular: Çalışmaya toplam 527 hasta dahil edildi. Çalışmaya dahil edilen hastaların %31,1’i (n=164) erkek,%68,9’u (n=363) ise kadındı. Çalışmaya dahil edilen hastaların %51,6’sı (n=272) COVID-19 negatif, %48,4’ü (n=255) ise COVID-19 pozitifti. Hastaların COVID-19 tanıları ile kan grupları arasında anlamlı bir farklılık izlenmedi (p=0,799). Hastaların COVID-19 olma durumu ile Rh faktörü arasında anlamlı bir farklılık izlenmedi (p=0,240). COVID-19 pozitif grupta, lenfosit ve CRP değerlerinde anlamlı farklılık izlenmezken (p>0,05); hemoglobin (p=0,028) ve WBC (p=0,014) değerlerinde anlamlı farklılıklar izlendi. Sonuç: Çalışma sonuçlarında ABO kan grubu ve Rh grubu açısından COVID-19 pozitif ve negatif hastalar açısından anlamlı bir fark olmadığı tespit edildi. Bununla birlikte, AB kan grubu olan PZR pozitif hastaların, WBC ve hemoglobin düzeylerinin diğer kan gruplarına göre anlamlı olarak düşüklük tespit edilmiştir. COVID pozitif hastaların kan grupları ile laboratuvar parametrelerinin ilişkisini açıklayabilmek için ileride yapılacak daha geniş kapsamlı araştırmalara ihtiyaç vardır.Öğe COVID-19 Olası/Kesin Tanılı Hastalarda Serbest Radikal Ve Antioksidan Enzim Düzeylerinin Değerlendirilmesi(2023) Davran, Fatih; Hacıoğlu, Ceyhan; Alpay, Merve; Yıldız Gülhan, Pınar; Öztürk, C. Elif; Ince, Nevin; Unlu, Elif NisaAmaç: Koronavirüs hastalığı 2019 (COVID-19), küresel halk sağlığını tehdit eden ve bir pandemiye yol açan karmaşık bir hastalık olmasına rağmen, hastalığın patogenezinde yer alan pro-oksidan/oksidan dengesizliğinin katkıları yeterince araştırılmamıştır. Bu nedenle, bu çalışmanın amacı, COVID-19 hastalarında sigara kullanımının oksidatif stres ve antioksidan savunma sistemi biyobelirteçleri üzerindeki etkilerini değerlendirmektir. Gereç ve Yöntemler: Çalışmaya katılan kişiler 4 gruba ayrıldı: (Kontrol grubu) COVID-19 tanısı olmayan ve sigara kullanmayan 45 sağlıklı birey, (Grup 2) COVID-19 tanısı olmayan ve sigara kullanan 45 birey, (Grup 3) COVID-19 tanılı ve sigara kullanmayan 45 hasta, (Grup 4) COVID-19 tanılı ve sigara kullanan 45 hasta. Katılımcıların serumlarındaki D-dimer, nitrik oksit (NO), glutatyon redüktaz (GR), süperoksit dismutaz (SOD), katalaz (CAT), malondialdehid (MDA), total antioksidan seviyeleri (TAS) ve total oksidan seviyeleri (TOS) seviyelerini ticari kitler kullanarak ELİSA yöntemine göre analiz edildi. Bulgular: COVID-19 tanısı alan kişilerdeki D-dimer seviyelerinde anlamlı bir artış söz konusudur (pÖğe The Effect of Continuous Positive Airway Pressure (CPAP) Therapy on Serum Caspase-3 Level in Patients with Obstructive Sleep Apnea (OSA)(Springer Heidelberg, 2024) Kaypak, Mustafa Kemal; Annakkaya, Ali Nihat; Davran, Fatih; Gulhan, Pinar Yildiz; Yuregir, UgurIntroductionIntermittent hypoxemia has an important role in the physiopathogenesis of obstructive sleep apnea (OSA) complications. Increased apoptosis due to intermittent hypoxemia may be an important clinical entity in OSA. In this study, we aimed to evaluate caspase-3 enzyme level, which is an indirect marker of increased apoptosis in patients with OSA and to evaluate the effect of OSA treatment with continuous positive airway pressure on caspase-3 enzyme level.Materials and methodsThis study included 141 consecutive patients admitted to the sleep-disordered breathing laboratory within 6 months. Caspase-3 was measured in routine blood samples obtained on the morning of polysomnography (PSG) performed at night. The compliance of the patients to CPAP treatment was evaluated and caspase-3 levels were checked again after treatment.ResultsA total of 141 patients, 39 females (27,7%) and 102 males (72,3%) were included in the study. The mean age of the patients was 49 +/- 12 years (min-17, max-77). According to PSG results, OSA was detected in 95.7% (135/141) of the cases. Mild OSA was 35 (24.8%), moderate OSA 39 (27.7%) and severe OSA 61 (43.3%) cases. Median caspase-3 enzyme levels were similar in men and women in the study group. There was no statistically significant difference in hemogram parameters and caspase-3 enzyme levels between the groups divided according to the presence and severity of OSA. It was determined that caspase-3 enzyme level did not change significantly after 3 months of CPAP treatment in OSA compared to pretreatment. Caspase-3 was found to have a negative correlation with both the percentage of daily use of CPAP therapy and the percentage of CPAP device use for more than 1 h per night. It was found that the control caspase-3 level decreased statistically significantly as the percentage of daily use of CPAP therapy increased (r = -0.397, p = 0.030). It was found that the control caspase-3 level decreased statistically significantly as the percentage of CPAP therapy use for more than 1 h per night increased (r = -0.411, p = 0.024).ConclusionThe results of this study did not reveal a relationship between the severity of OSA and caspase-3 levels. However, blood caspase-3 levels decreased as treatment compliance increased, suggesting that CPAP treatment may correct increased apoptosis in OSA. There is a need for more comprehensive studies on this issue.Öğe The Effect of Vitamin D Level on the Clinical Situation in COVID-19 Patients(Duzce Univ, Fac Medicine, 2023) Davran, Fatih; Hacioglu, Ceyhan; Kayabasi, Eda; Keskin, Banu Humeyra; Duran, Pelin Kamuran; Unlu, Nisa; Escan, ElifObjective: Vitamin D plays an important role in maintaining the integrity of mucosal barriers and in natural and acquired immunity. In the COVID-19 pandemic, the strength of personal immunity is very important in the course of the disease, despite the presence of variants of the virus or vaccination status. Method: In this study, we investigated the relationship between the clinical course and vitamin D levels of outpatient and inpatient follow-up patients admitted to our hospital due to COVID-19. A total of 94 patients, 47 outpatients and 47 inpatients, were included in the study. Results: The mean age and gender distributions of both groups were similar. Vitamin D levels were found to be normal in only 7 of 94 patients who were followed up in our hospital due to COVID-19. Patients with vitamin D levels >= 30 were significantly lower than those with <10 and 10-29.9 (p<0.01 for each). Hospitalized patients (71%) with vitamin D levels <10 were significantly higher than those (0%) with vitamin D levels >= 30. Additionally, the outpatients (29%) with vitamin D levels <10 were significantly lower than those (100%) with vitamin D levels >= 30. Conclusion: The data showed that vitamin D deficiency may be associated with the severe clinical course of COVID-19, even in patients without comorbidities, and may also be one of the predisposing factors resulting in death in COVID-19. As a result, vitamin D levels in COVID-19 patients may be important for the course of the disease.Öğe The evaluation of both the expression and serum protein levels of Caspase-3 gene in patients with different degrees of SARS-CoV2 infection(Wiley, 2021) Gulhan, Pinar Yildiz; Eroz, Recep; Ataoglu, Ozlem; Ince, Nevin; Davran, Fatih; Ozturk, Cihadiye Elif; Balbay, Oner AbidinTo evaluate the effects of Caspase-3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 41 individuals (male: 21; female: 20) with SARS-CoV-2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 +/- 18.937 years. Significant differences were detected among all groups for CASP3 2-Delta Delta Ct (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 2-Delta Delta Ct levels and hemoglobin (p = 0.023), between CASP3 2-Delta Delta Ct levels and C-reactive protein (CRP) (p = 0.001), between CASP3 2-Delta Delta Ct levels and ferritin (p = 0.003), between CASP3 2-Delta Delta Ctlevels and lactate dehydrogenase (p = 0.001), and between CASP3 2-Delta Delta Ct levels and SpO(2) (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO(2) was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS-CoV-2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease.Öğe Kolorektal Kanser Hücrelerinde Boraksın Gpx4/ACSL4 Sinyal Yolu Aracılığıyla Sitotoksik Etkileri(2023) Hacıoğlu, Ceyhan; Davran, FatihAmaç: Kolorektal kanser (CRC), kansere bağlı ölümlerin yaklaşık %10'unu oluşturmasıyla, malignite yönünden üçüncü ve kansere bağlı ölümlerde ikinci sırada yer almaktadır. Ferroptoz, CRC dahil çok sayıda kanserin tedavisinde ilaç direncini önlemede terapötiklerin anti-kanser etkinliğini arttırabilecek potansiyel demire bağlı hücre ölüm yolağıdır. Bu çalışmada CRC hücrelerinde ferroptozu sinyal yolağı üzerinden boraksın anti-proliferatif etkilerini araştırmak amaçlandı. Gereç ve Yöntemler: Öncelikle, boraksın sitotoksik konsantrasyonları (0-64 mM aralığında) 3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazolyum bromür (MTT) testi ile belirlendi. Daha sonra sitotoksik boraks konsantrasyonları ile 24 saat inkübe edilen HCT-116 hücrelerinde glutatyon peroksidaz 4 (GPx4), açil-KoA sentetaz uzun zincirli aile üyesi 4 (ACSL4), malondialdehit (MDA) ve 8-hidroksideoksiguanozin (8-OHdG) seviyeleri belirlendi. Bulgular: 1 ve 4 mM boraks konsantrasyonları hücre canlılığını etkilemezken, 8 mM ve üzerindeki boraks konsantrasyonları HTC-116 hücrelerinde canlılığı anlamlı şekilde düşürmüştür (pÖğe Multidrug-Resistant Gram-Negative Bacteria Rate and Risk Factors in the Neonatal Intensive Care Unit: A Single-Center Ten- Year Experience(Duzce Univ, Fac Medicine, 2023) Cakmak, Hatice Mine; Yekenkurul, Dilek; Sengun, Zehra; Yener, Selvi; Duran, Pelin Kamuran; Davran, Fatih; Kocabay, KenanObjective: Multidrug resistance (MDR) in gram-negative neonatal infections is difficult to manage, and the risk factors differ among different studies. Therefore, we aim to investigate the demographics, mortality, MDR status of gram-negative isolates, and risk factors for MDR gram-negative infections.Methods: We conducted a retrospective single-center study about MDR gram-negative infections in neonates between January 2012-January 2022 at Duzce University Hospital in Turkey. This study evaluates neonates with MDR gram-negative infections' risk factors and clinical features. All analyses were performed using IBM SPSS V23. In addition, univariate analyses and multivariate logistic regression models were studied to determine MDR's risk factors.Results: Of 107 gram-negative bacteria, 41 (38.3%) accounted for Enterobacter, 30 (28%) for Klebsiella pneumonia, and 22 (20.6%) for Escherichia coli. Additionally, 61 (56.5%) were MDR microorganisms. Among the susceptibility tests performed for selected isolates, 41 (77.4%) had resistance to piperacillin, 57 (75%) showed resistance to amoxiclav, and 16 (72.7%) had cefoxitin resistance. In addition, carbapenemase resistance was found in 24 (43.6%) and meropenem resistance in 13 (36.1%). Colistin, aztreonam, and tigecycline resistances were the least frequent. In addition, the following dependent risk factors increased the multidrug resistance risk in gram-negative infections; late-onset sepsis 3.547 fold (p=0.005), use of mechanical ventilation 3.143 fold (p=0.007), blood transfusion 3.587 fold (p=0.013), bronchopulmonary dysplasia 6.702 fold, (p= 0.015) and total parenteral nutrition 5.591 fold (p=0.001), lower gestational age 1.122 (1/0.891) fold (p=0.026), and birth weight 1.001 (1/0.999) fold, (p=0.013). Similarly, antibiotherapy duration was significantly higher in the MDR group than in the non-MDR group.Conclusions: The reported risk factors for MDR in gram-negative neonatal infections are all dependent risk factors. Hence clinicians must be alert to all potential risk factors.Öğe Perilipin-5 as a potential new biomarker in patients with liver disease and impaired De Ritis ratio(Cukurova Univ, Fac Medicine, 2021) Şahin, İbrahim Ethem; Hacıoğlu, Ceyhan; Davran, Fatih; Alpay, MervePurpose: Liver dysfunctions are one of the most prevalent and deadly diseases worldwide. The De Ritis ratio, which is obtained by proportioning serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT), has been suggested to be a precious marker to assess the prognosis of liver diseases. This study was to investigate the relationship between perilipin 5 (PLIN5) levels and De Ritis ratio in patients with liver disease. Materials and Methods: There were 3 groups: control (Group1; n=20), hepatic patients with normal De Ritis ratio (Group2; n=35) and hepatic patients with impaired De Ritis ratio (Group3; n=35). De Ritis rates of all patients were determined according to the serum aspartate aminotransferase (AST)/serum alanine aminotransferase (ALT) results. Additionally, PLIN5 was spectrophotometrically analyzed from serum samples. Results: There is no significant difference between the groups in terms of age and gender. PLIN5 levels increased by 2.6 and 3.8 times in Group2 and Group3, respectively. De Ritis ratio was significantly increased in the Group3 compared the control, and enhanced PLIN5 levels was correlated with De Ritis ratio in the Group3. There was a significant positive correlation between De Ritis ratio and PLIN5 levels. Conclusion: PLIN5 levels together with De Ritis rate in liver patients may be used as a prognostic marker. Furthermore, this relationship could be a useful method in the follow-up of liver diseases.Öğe The predictive role of laboratory parameters in cardiovascular risk assessment in obese(Lippincott Williams & Wilkins, 2023) Kaya, Abdulkadir; Gamsizkan, Zerrin; Kaya, Nursel; Davran, FatihThe significance of cardiovascular diseases in mortality is indisputable. It is well-established that cardiovascular diseases are more prevalent among individuals with obesity. This study aimed to determine the predictive value of easily accessible hematological and biochemical parameters in assessing cardiovascular risk among obese patients. The study was designed as an observational retrospective. Department of Family Medicine, study was carried out between 25/06/2022 to 30/10/2022. The data of 439 obese patients were analyzed retrospectively. Using the online Heart Score system, the patients were classified into low, medium, high, and very high cardiovascular risk categories. The hemogram and certain biochemistry values of the patients at the time of admission were examined. Receiver operating characteristic (ROC) analyses were conducted to discriminate cardiovascular risk classes based on laboratory values. Markers with high diagnostic value, including a high area under the curve (AUC) value, sensitivity, and specificity, were presented. Significant differences were observed between the groups in terms of age, systolic blood pressure, diastolic blood pressure, total cholesterol, low-density lipoprotein, glucose, HbA1c, hemoglobin, platelet count, neutrophil (NEU) count, and platelet-lymphocyte ratio parameters (P < .05). The white blood cell count and NEU count of patients in the high-risk groups were found to have significantly higher AUC values compared to the moderate-risk group (AUC values of .737 and .779, respectively). The white blood cell and NEU parameters were found to have a positive predictive value in estimating the degree of cardiovascular risk. These parameters can potentially serve as biomarkers in identifying individuals at high risks for cardiovascular diseases.Öğe The Use of Predictive Laboratory Tests in Rapid Triage of COVID-19 Pandemic Outpatient Clinic Patients(Clin Lab Publ, 2022) Gamsızkan, Zerrin; Kaya, Abdulkadir; Davran, Fatih; Çalışkan, Emel; Ünlü, Elif Nisa; Ünal, SafaBackground: Patients who come to the emergency pandemic outpatient clinic with a pre-diagnosis of COVID-19 are still a burden on the health system. Rapid triage of patients is important to reduce transmission. The aim of this study is to evaluate the biochemistry and hemogram results of real-time reverse transcription-polymerase chain reaction (RT-PCR) positive and negative patients in the emergency pandemic outpatient clinic and to investigate predictive values of the initial tests that will help to make rapid diagnosis. Methods: Patients who applied to the emergency pandemic outpatient clinic with the suspicion of COVID-19 be-tween November 01, 2020 and January 01, 2021 were evaluated with RT-PCR and laboratory examinations. Results: A total of 551 patients were included in the study. The mean age of the patients was 50.31 +/- 18.47 (min. 18 - max. 94), and 47.2% (n = 260) of the patients included in the study were male and 52.8% (n = 291) were female. In the comparison of hemogram parameters, we found that mean platelet volume (MPV) was significantly higher (p = 0.023), whereas white blood cell (WBC), platelet counts (PLT), lymphocyte and neutrophil values were significantly lower in RT-PCR positive patients (p < 0.001). There were no significant differences between the PCR positive and negative patients in terms of other parameters. In the comparison of biochemical parameters, we found that lactate dehydrogenase LDH (p = 0.001), creatinine (p = 0.002), and AST (p < 0.001) values were significantly higher in PCR positive patients, while there were no significant differences in terms of other biochemical parameters (p > 0.05). Conclusions: Our study results show that the practical quick-look hemogram and MPV can be used as a specially evaluated parameter in the rapid management of the first application COVID-19 patients. In addition, biochemically high levels of LDH and creatinine can be used to guide the clinician in terms of early hydration of the patient with a pre-diagnosis of COVID-19 to alleviate acute kidney damage.
