Yazarlar
- Suleyman, Halis(167)
- Mammadov, Renad(95)
- Türkeş, Cüneyt(84)
- Aydin, Sonay(83)
- Altuner, Durdu(74)
- Suleyman, Bahadir(68)
- Isik, Arda(67)
- Beydemir, Şükrü(66)
- Kantarci, Mecit(64)
- Kurt, Nezahat(57)
- Demir, Yeliz(54)
- Bulut, Seval(51)
- Arslan, Yusuf Kemal(50)
- Sofu, Hakan(50)
- Coban, Taha Abdulkadir(49)
- Karakeçili, Faruk(47)
- Altay, Ahmet(46)
- Huyut, Mehmet Tahir(46)
- Aydin, Suleyman(45)
- Türkmenoğlu, Burçin(45)
- Kuzucu, Mehmet(40)
- Yazici, Gulce Naz(40)
- Peker, Kemal(39)
- Algul, Oztekin(38)
- Cicek, Betul(37)
- Mertoglu, Cuma(36)
- Camurcu, Yalkin(35)
- Suleyman, Zeynep(34)
- Bozkurt, Aliseydi(32)
- Mendil, Ali Sefa(32)
- Gunay, Murat(31)
- Gözcü, Sefa(31)
- Köksal, Ekrem(31)
- Yuca, Hafize(31)
- Dilek, Esra(30)
- Karakurt, Papatya(30)
- Ozcicek, Fatih(30)
- Süleyman, Halis(30)
- Onk, Didem(29)
- Ucpunar, Hanifi(29)
Yayınlar
- MakaleAçık Erişim2025Comparison of various fragmentation methods of alpha-synuclein fibrils for establishing a Parkinson’s disease-like model in cell culture
Akyel, Hilal; Bahador Zırh, Elham; Zırh, Selim; Yazgi, Hare; Tel, Banu Cahide
Objectives: Alpha-synuclein (α-syn) fibrils, which are associated with Lewy-like inclusions, are currently utilized in the modeling of Parkinson’s disease (PD). The fibrils require a length shorter than 100 nm to uptake intracellularly. Our study aims to determine the optimal probe sonication parameters that can be applied in diverse laboratory settings for the fragmentation of fibrils to lengths of ≤100 nm. Methods: In our study, human wild-type α-syn fibrils were sonicated with 1, 3, and 5 s-on/off pulse applications at varying ambient temperatures (room temperature, ice, and ice-surrounded by dry ice) for a duration of 1 min, with a total of 40 and 60 cycles, respectively. The length of the fibrils was quantified by transmission electron microscopy imaging. The total α-syn in SH-SY5Y cells was detected by immunofluorescence staining following the administration of fragmented fibrils after 2-, 4-, and 6-day incubations. Results: Although fragmentation was observed under all conditions, fibrils of ≤100 nm were obtained with a 5 s-on/off pulse in ice and ice-surrounded by dry ice ambientes. The fibril length of ≤100 nm was observed on days 2 and 4; however, the highest level of observed intensity was detected on day 6. Conclusions: The application of 5 s-on/off consecutive pulses in ice, and ice-surrounded by dry ice ambientes are more effective methods for fragmenting and internalizing fibrils, thereby forming a reproducible cellular PD-like model. In summary, our study provides a significant contribution to the development of an economical and effective sonication methodology for the fragmentation of fibrils in a diverse of laboratory settings.
- MakaleYalnız künye2025Design and synthesis of new HCV NS3/4A protease inhibitors to effective against drug resistance
Oksuz, Zehra; Aktekin, Mine Buga; Alagoz, Mehmet Abdullah; Kuzucu, Mehmet; Serin, Mehmet Sami; Algul, Oztekin
HCV NS3/4A protease is a crucial target for antiviral therapy, but resistance remains a significant challenge. Understanding substrate recognition is key to developing effective inhibitors. The aim of this study was to investigate four new compounds (10–12 and 13) that mimic natural substrate binding. Compound activities were determined with enzymatic assays and anti-proliferative activities were evaluated. Compound 12 exhibited the highest potency with an IC50 of 17.78 μM and a Ki value of 16.39 μM. All compounds demonstrated moderate to high anti-proliferative activity against HFF-1 and HepG2 cells, with 12 and 11 showing the most potent effects. In silico studies revealed that compounds 11 and 12 formed stable complexes with the HCV NS3/4A protease, establishing significant interactions with key residues of the catalytic triad. Their docking scores and molecular dynamics simulations were comparable to those of the reference molecule, simeprevir. These findings suggest that compounds 10–12 and 13 hold promise as potential therapeutic agents against HCV, warranting further investigation.
- MakaleYalnız künye2025Antidiabetic and antioxidant properties of Berberis crataegina DC.: In vitro and in vivo studies, and phytochemical analysis
Yılmaz, Rabia; Aktaş, Mehmet; Şimşek, Samed
Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, often results in complications that impact vital organs such as the liver and kidneys. Due to the high morbidity and mortality of diabetic complications, there is a need for alternative therapeutic strategies. Therefore, this study evaluates the therapeutic effects of Berberis crataegina, which contains bioactive compounds with potential hepatoprotective and nephroprotective benefits, on liver and kidney function in diabetic rats. Diabetes was induced using alloxan, and after a 19-day treatment period, biochemical and histopathological analyses were performed on blood and tissue samples. Antioxidant activity was evaluated by DPPH and FRAP assays, and total phenolic and flavonoid contents were determined, while LC-MS/MS analysis identified the major bioactive compounds. In diabetic rats, liver enzymes significantly increased, and serum insulin levels decreased, indicating hepatic and pancreatic dysfunction. However, treatment improved these parameters, reduced HbA1c levels, and led to improved glycemic control. Histopathological analysis showed severe renal and hepatic damage in diabetic rats, which was significantly mitigated by treatment. Antioxidant assays demonstrated strong free radical scavenging ability, as shown by DPPH and FRAP activities, which correlated with high total phenolic and flavonoid content. In addition, LC-MS/MS analysis identified quinic acid, protocatechuic acid, chlorogenic acid, and caffeic acid as the major bioactive compounds, further supporting the plant's potent antioxidant and antidiabetic properties. These findings suggest that Berberis crataegina has significant potential to protect against diabetes-induced liver and kidney damage and improve glycemic control, highlighting its therapeutic potential for diabetes management.
- MakaleAçık Erişim2025Gallic acid’s protective mechanisms against acrylamide-induced pulmonary injury: in vivo and in silico insights into the Nrf-2/HO-1/NFκB pathway modulation
Bolat, Merve; Tekin, Samet; Bolat, İsmail; Atasever, Aslıhan; Çinar, Burak; Dağ, Yusuf; Şengül, Emin; Yildirim, Serkan; Warda, Mohamad; Çelebi, Fikret
Acrylamide (ACR) is a toxic compound formed during the heating of tobacco and starchy foods, contributing to increased reactive oxygen species (ROS) levels and significant health risks. This study evaluates the protective effects of gallic acid (GA), a natural polyphenol with potent antioxidant and anti-inflammatory properties, against ACR-induced lung injury. Fifty male rats were divided into five groups: Control, ACR, GA50 + ACR, GA100 + ACR, and GA100. Lung tissues were analyzed biochemically, histopathologically, immunohistochemically, and via immunofluorescence. GA exhibited dose-dependent protective effects by enhancing antioxidant defenses through Nrf-2 (43% increase) and HO-1 activation and reducing lipid peroxidation markers (MDA decreased by 38%). GA also suppressed pro-inflammatory mediators (TNF-α reduced by 35%) and restored anti-inflammatory levels by modulating the NF-κB pathway. Furthermore, GA reduced apoptosis (Caspase-3 activity decreased by 30%) and preserved lung tissue integrity by mitigating oxidative DNA damage (8-OHdG levels reduced by 29%) and pro-apoptotic signaling (Bax levels reduced by 34%). Computational analyses demonstrated GA's interaction with the KEAP1 protein, supporting its role in activating the KEAP1-Nrf2 pathway. These findings highlight GA's antioxidant, anti-inflammatory, and anti-apoptotic properties, suggesting its therapeutic potential for protecting against ACR-induced lung injury and paving the way for future research in lung health and toxicology.
- MakaleAçık Erişim2025Evaluation of corneal endothelial parameters in patients with methamphetamine use disorder
Koc, Hakan; Simsek, Meltem Hazel; Akkus, Mustafa
Purpose: To determine the structure and properties of corneal endothelial cells in patients with methamphetamine use disorder. Material and method: The cross-sectional study included 33 eyes of 33 patients with methamphetamine (meth) use disorder and 33 eyes of 33 healthy subjects. Mean cell density, coefficient of variation, hexagonality ratio, maximum cell area, normal cell area, minimum cell area, and mean cell area were evaluated by non-contact specular microscopy. The parameters recorded in each group were compared. Results: The mean ages of the individuals in the meth and control groups were 32.36 ± 7.68 and 31.18 ± 4.79 years, respectively. The mean daily meth dose was 0.306 ± 0.154 g, mean weekly meth use was 2.70 ± 1.46 days, and mean total meth dose was 302.70 ± 296.04 g in the meth group (p = 0.456). The mean corneal endothelial cell count (ECD) values were 2692.82 ± 372.52 in the Meth group and 2869.7 ± 261.31 in the control group (p = 0.76). The mean coefficient of variation (CV) values were 30.76 ± 3.41 in the meth group and 29.21 ± 2.55 in the control group (p = 0.042). Mean hexagonality ratio (%) (HEX) values were 57.73 ± 9.38 in the meth group and 57.88 ± 9.96 in the control group (p = 0.949). A positive correlation was observed between CV and meth dose and duration of meth use (p = 0.011, p = 0.000, respectively). Conclusion: The results of our study indicate that the corneal endothelium is subjected to stress in patients with a methamphetamine use disorder. The CV value suggests that the usability of methamphetamine as a quantitative indicator in the evaluation of possible corneal endothelial toxicity is an area that needs to be supported by further research.
- MakaleAçık Erişim2025A TIME SERIES ANALYSIS OF THE RELATIONSHIP BETWEEN AIR QUALITY CONCENTRATION AND MATERNAL-NEONATAL HEALTH IN TÜRKİYE: A RETROSPECTIVE STUDY BASED ON PM, NOx, SO2, AND O3 PARAMETERS
Pоlаt, Tunсаy; Özеr, Mustаfа; Çеlik, Hаkаn; Bulut, Hüsеyin
Air pollution is a significant global public health issue, and pollutants such as PM2.5, PM10, SO2, NO2, CO, and O3 adversely affect maternal and infant health. This study aims to contribute to environmental health policies by retrospectively analyzing the relationship between air quality index values and maternal and infant mortality in Turkey from 2020 to 2025 through time series analysis. Air quality data were obtained from the National Air Quality Monitoring Network of the Ministry of Environment, Urbanization and Climate Change, while mortality statistics were sourced from the Turkish Statistical Institute. Annual averages of air pollutants, particularly PM10 and PM2.5, were calculated, and their relationship with mortality rates was evaluated using correlation and simple regression analyses. According to normality tests, infant mortality rate and the mortality rate among women of reproductive age were normally distributed, whereas under-five mortality and live birth rates were not. Accordingly, Pearson correlation was used for normally distributed variables, and non-parametric correlation methods were applied to non-normally distributed ones. Significant associations were found between PM10 and infant mortality in 2021 and 2023 (p < 0.05), and between PM2.5 and both infant mortality in 2023 and the five-year aggregate data (p < 0.05). Other pollutants, such as NO2, NOx, and NO, also showed significant associations with infant deaths and maternal mortality in women of reproductive age (p < 0.05). The study found that exposure to PM10, PM2.5, and NO2 may increase infant mortality, while exposure to NOx and NO may contribute to increased mortality in both infants and women of reproductive age. These findings highlight the severe health risks posed by air pollution to vulnerable populations, emphasizing the urgent need for preventive measures, particularly for infants and women of childbearing age.
- MakaleAçık Erişim2025Prediction of Pedestrian Traffic Accident Severity and Evaluation of Driver and Pedestrian Faults
Baş, Fatih İrfan
This study investigated pedestrians involved traffic accidents with the aim of classifying the severity of accidents based on the number of injured pedestrians using machine learning algorithms, including AdaBoost, Gradient Boosting, XGBoost, K-Nearest Neighbors (KNN), Logistic Regression, Support Vector Classifier, Decision Tree, and Random Forest. The Random Forest model was identified as the best model for classifying pedestrian-involved traffic accidents, achieving high predictive accuracy of 95%, an F1 score of 0.95, and demonstrating low error metrics. The research analyzed both driver and pedestrian faults, alongside factors such as the presence of pedestrian crossings, intersection type, driver age, time of day, month and seasonal variations. The results revealed that accidents at locations without intersections were primarily caused by driver faults, such as speeding, while pedestrian faults, such as crossing at unintended locations, also significantly contribute to the overall accident rate. The findings offered valuable insights into the characteristics of pedestrian accidents to improve traffic safety and reduce pedestrian injuries and fatalities.
- MakaleAçık Erişim2025Plasma phthalate levels in children with speech delay
Yaman Artunç, Nihal; Yirün, Anıl; Yıldıztekin, Gizem; Erkekoğlu, Pınar; Zengin Akkuş, Pınar; İlter Bahadur, Evin; Özdemir, Gökçenur; Özmert, Elif N.
Speech delay is a common developmental concern. Environmental pollutants like phthalates, recognized as endocrine disruptors, may be a risk factor. We aimed to investigate the relationship between phthalates and speech delay. The study comprised 50 children with isolated speech delay and 40 healthy children of similar ages. Children were assessed for speech delay risk factors and phthalate exposure sources. High-pressure liquid chromatography examined plasma di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP) and dibutyl phthalate (DBP) levels. DEHP, MEHP, and DBP levels varied between study and control groups: 0.377 (0.003–1.224 µg/ml), 0.212 (0.007–1.112 µg/ml) (p = 0.033), 0.523 (0.031–2.477 µg/ml), 0.152 (0.239–2.129 µg/ml) (p < 0.001), and 0.395 (0.062–1.996 µg/ml) and 0.270 (0.006–0.528) (p = 0.004). Multiple linear regression was used to adjust phthalate levels and speech delay risk factors. DEHP levels were did not differ significantly between the groups (p = 0.233), whereas MEHP and DBP levels were considerably higher in the study group (p < 0.001). The statistically significant rise in plasma phthalate levels in children with speech delay implies phthalate exposure may be a risk factor, but further epidemiological research is needed.
- MakaleAçık Erişim2025Relationship Between the Mandibular Cortical Index and Periodontitis Stage/Grade: A Retrospective Radiographic Study; [Mandibular Kortikal İndeks ile Periodontitis Evre/Derecesi Arasındaki İlişki: Retrospektif Radyografik Çalışma]
Okumuş, Ömer Faruk; Acipinar, Şükran
Background: In the literature, the relationship of the mandibular cortical index (MCI) with the stage and grade of periodontitis has not yet been inves-tigated. This study aimed to examine the relationship between the stage and grade of periodontitis and MCI according to the current classification of periodontal disease. Methods: A total of 199 patients (119 females, 80 males) were included in this study. The study population consisted of patients with periodontitis and controls without periodontitis. The stage and grade of the patients with per-iodontitis were determined according to the criteria of the “2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions”. Patient records, including periodontal data and panoramic ra-diographs, were used for this classification. The MCI values of the patients were also recorded by evaluating the same panoramic radiograph. The Pear-son chi-square test was used to compare categorical data according to groups, and multiple comparisons were undertaken with the Bonferroni-cor-rected Z test. Results: The non-periodontitis (NP) group had the highest C1 type bone rate (p<0.001). The C3 rate of the stage Ⅲ/Ⅳ group was significantly higher com-pared to all the remaining groups (stage Ⅰ, stage Ⅱ, and NP) (p<0.001). The C3 rate was significantly higher in the grade C group than in the grade B and NP groups (p<0.001). Conclusions: The data obtained from this study suggest that there is a posi-tive relationship between the stage and grade of periodontitis and MCI.
- MakaleAçık Erişim2025A Meta-Analysis of Self-Management Interventions in Teaching Daily Living Skills to Autistic Individuals
Aydin, Orhan; Sulu, Mehmet D.; Ari-Arat, Ceren
The current study aimed to conduct a systematic review and meta-analysis of self-management interventions for teaching daily living skills to autistic individuals. This study accessed the corresponding studies by doing a search in six databases. 14 articles and one dissertation met the inclusion criteria. The included studies were first analyzed descriptively and coded according to quality indicators using What Works Clearinghouse (WWC) standards. Second, the effect sizes of the included studies were calculated using two different effect size measures (i.e., Tau-U and performance-criteria-based effect size values [PCES]). Third, these analyses were also conducted for generalization and maintenance data. Of 15 studies included in this review, nine met the WWC standards with and without reservations. Tau-U analyses were conducted for 14 studies, whereas PCES values were calculated for only eight studies with mastery criteria. The findings indicated that the self-management interventions had a.93 CI95 (.80, 1) overall effect size for Tau-U with a very large effect. On the other hand, the overall effect size for the PCES values indicated a moderate effect with.99. The weighted effect sizes in generalization and maintenance phases were very large for Tau-U; however, moderate to high effects for PCES. Although self-management interventions showed diversity, one of the domains of daily living skills (i.e., community living skills) has not been studied in the field. Notably, among the studies in our review, the last ones are from 2019. Detailed findings from descriptive analyses and two different effect size calculations are discussed, and recommendations for future studies are given.
- DüzeltmeAçık Erişim2025Correction: Morphometric features, variability and clinical significance of coracoclavicular tuberosity (Surgical and Radiologic Anatomy, (2025), 47, 1, (77), 10.1007/s00276-025-03581-4)
Akbulut, Yalçın; Karakas, Asli Beril; Yarar, Burhan; Sunar, Mukadder
In this article the author name Asli Beril Karakas was incorrectly written as Aslı Beril Karakaş Tanır. The original article has been corrected.
- MakaleAçık Erişim2025Aflatoxin B1 levels, dietary exposure and cancer risk assessment in sesame and nut-based foods in Türkiye
Aydemir Atasever, Meryem; Güler İnce, Mukaddes Beyza; Alkan Polat, Betül; Özlü, Hayrunnisa; Atasever, Mustafa
Aflatoxin B1 (AFB1), a highly toxic mycotoxin commonly found in oilseeds and nuts, poses serious public health and economic risks. Türkiye's climatic conditions are conducive to AFB1 contamination, particularly in sesame- and nut-based foods. This study investigated the presence of AFB1 in 100 widely consumed samples of tahini, tahini halva, hazelnut paste, and peanut paste. AFB1 was detected in 67% of the samples, with exceedances of the European Commission (EC) limit (2 µg/kg) notably high in tahini halva (80%) and peanut paste (60%); in contrast none of the hazelnut paste samples surpassed the legal threshold. The findings indicated that no samples of hazelnut paste exceeded the legal limits set by the EC. However, 4 tahini (13.33%), 24 tahini halva (80%), and 12 peanut paste (60%) samples exceeded the EC limits. Dietary exposure estimates were calculated based on lower bound (LB), middle bound (MB), and upper bound (UB) contamination scenarios. Margin of exposure (MOE) values for tahini halva were consistently below the safety threshold of 10,000, suggesting a possible health concern. The estimated annual incidence of hepatocellular carcinoma (HCC) due to AFB1 exposure ranged from 0.000888 to 0.00219 cases per 100,000 adults, remaining below European Food Safety Authority’s (EFSA) reference risk levels. These findings underscore the need for targeted surveillance and stricter regulatory controls on sesame-based products, particularly tahini halva, within national food safety frameworks.
- MakaleAçık Erişim2025Evaluation of Lacrimal Drainage System in Patients with Unilateral Nasolacrimal Duct Obstruction by Computerized Tomography
Kazanci, Burcu; Gokharman, Dilek; Aydin, Sonay; Eroğlu, Fatma Çorak; Apaydin, Nihal
Purpose: This study aimed to evaluate morphometric measurements relevant for surgery in patients with unilateral nasolacrimal duct occlusion on CT images, comparing the sides with and without occlusion. Methods: Paranasal sinus computed tomography images of 37 patients (28 females, 9 males) who presented with unilateral epiphora and underwent external dacryocystorhinostomy were retrospectively analyzed. Two radiologists with 25 and 10 years of experience performed measurements. The nasolacrimal duct length, transverse diameter of its narrowest part, vertical length of the lacrimal fossa, thickness of the anterior lacrimal crest, its distance to anterior ethmoidal cells, thickness of the intranasal lateral mucosa, frontonasal angle, and distance between the frontozygomatic sutures were measured and compared bilaterally. Results: The narrowest diameter of the nasolacrimal duct on the occluded side was significantly narrower than on the intact side. There were no significant differences between the occluded and patent sides for other measurements or the interclass correlation results between the two radiologists’ evaluations. Conclusion: Stenosis of the nasolacrimal duct on both sides is observed clinically as chronic dacryocystitis in the same patient. Since the bony window for external dacryocystorhinostomy is determined based on the lacrimal fossa’s vertical width, the data from our study are crucial for surgical planning.
- MakaleYalnız künye2025ADME predictions and molecular docking insights for novel Gypsogenin–chalcone hybrids and chalcones as antitumor and antimicrobial agents
Emirdağ, Safiye; Ulusoy, Nafia Gökçe; Kahriman, Nuran; Serdaroğlu, Vildan; Türkmenoğlu, Burçin; Yaylı, Nurettin
The cytotoxicity and antimicrobial efficacy of novel semisynthesized Gypso-Anhd chalcone hybrids (C1–C27) and methoxy‑substituted hydroxychalcones (A1–A27) were evaluated in the following six cancer cell lines: A549, HeLa, HEK293, SHSY5Y, MDA-MB-231, and PANC-1. These derivatives exhibited significant antimicrobial activity, against G+ bacteria (Bacillus subtilis, Enterococcus faecalis, and Staphylococcus aureus), G- bacteria (Escherichia coli and Pseudomonas aeruginosa) and Candida albicans. Among hydroxychalcone derivatives, A19, A25, and A26, demonstrated superior antiproliferative activity compared doxorubicin, with IC50 values of 1.43 ± 0.02 μM (A19, A549), 1.04 ± 0.02 μM (A25, HeLa), 0.90 ± 0.14 μM (A25, HEK293), 0.25 ± 0.03 μM (A25, SHSY5Y), 1.18 ± 0.03 μM (A26, MDA-MB-231), and 0.99 ± 0.03 μM (A26, PANC-1). Likewise, hybrid derivatives C12, C14, and C26 exhibited higher antiproliferative activity than doxorubicin, with IC50 values of 1.33 ± 1.14 μM (C26, A549), 9.51 ± 0.03 μM (C12, HeLa), 4.09 ± 0.65 μM (C26, HEK293), 1.79 ± 0.09 μM (C12, SHSY5Y), 7.97 ± 0.84 μM (C26, MDA-MB-231), and 3.71 ± 0.49 μM (C14, PANC-1). Molecular docking studies confirmed target-specific interactions for all synthesized derivatives. ADME analyses indicated favorable pharmacokinetic profiles, while hydroxy and methoxy substitutions modulated bioactivity, highlighting their potential as anticancer drug candidates.
- MakaleYalnız künye2025Fluorenyl-phthalimide hybrids as potent aldose reductase inhibitors with selective anticancer activity: Rational design, synthesis, and molecular insights
Gundogdu, Saliha; Duran, Hatice Esra; Arslan, Mustafa; Çetinkaya, Büşra Demir; Türkeş, Cüneyt
Metabolic reprogramming in cancer cells creates actionable vulnerabilities for precision oncology. Aldose reductase (ALR2, AKR1B1; EC 1.1.1.21), a cytosolic NADPH-dependent oxidoreductase, has emerged as a multifunctional player in tumor progression, drug resistance, and oxidative stress modulation, yet remains underexploited as a cancer target. In this study, we report the rational design, synthesis, and biological evaluation of a focused series of fluorenyl-phthalimide carboxylic-acid hybrids (5a-5l) as dual-acting agents with selective anticancer potential and potent ALR2 inhibition. Among them, compound 5a exhibited the strongest ALR2 inhibition with a KI of 8.71 ± 0.81 nM, far surpassing the clinical comparator epalrestat (KI = 232.10 ± 14.42 nM). In MCF-7 and A549 carcinoma cells, 5a demonstrated moderate antiproliferative activity (IC50 = 52.04 μM and 192.91 μM, respectively) while sparing normal bronchial epithelial cells, indicating tumor selectivity. Molecular docking and MM-GBSA calculations (ΔGbind = −44.02 kcal/mol) revealed a consistent bidentate hydrogen bonding network supporting high-affinity binding involving Tyr48, His110, and Trp111, further stabilized by crystallographic water molecules. To explore structure-activity relationships, a Random Forest regression model was developed using 24 descriptors derived from QikProp. The model achieved strong predictive performance (Q2CV = 0.71), and SHAP analysis identified water/gas partition coefficient, skin permeability, and human oral absorption as the most influential features shaping inhibitory potency. In silico ADME/Tox profiling supported the drug-like nature of compound 5a, with no major CYP or hERG liabilities predicted. Collectively, these findings position 5a as a first-in-class ALR2-targeted anticancer lead, introducing a chemically novel and mechanistically validated chemotype for further development within the framework of metabolically targeted precision therapies.
- MakaleAçık Erişim2025Re-Examining the Dimensionality of a Disability Assessment Tool Using Exploratory Structural Equation Modeling (ESEM): A Preliminary Study in Low Back Pain
Hayme, Serhat; Gökmen, Derya; Kutlay, Şehim; Küçükdeveci, Ayşe A.
Background: Low back pain (LBP) profoundly impacts daily life, requiring assessment tools that capture its complex effects on the body and mind. This study explores a measurement tool designed to assess LBP disability, testing whether Exploratory Structural Equation Modeling (ESEM) better reveals its multidimensional nature compared to Confirmatory Factor Analysis (CFA). Methods: We analyzed data from 266 LBP patients using CFA and ESEM. The tool, developed from the items from existing scales, included 99 questions on body functions, activities, and participation. Using Mplus 8 software, we compared model fit and item connections. Results: Two main factors; “Body Functions” and “Activity-Participation” identified by CFA were tested using ESEM. While ESEM had slightly better fit compared to CFA model, many items linked across both factors which shows how pain and emotions overlap with daily activities. These results align with the International Classification of Functioning, Disability and Health (ICF) and reflect LBP’s broad impact. Conclusions: ESEM offers a broader understanding of LBP’s multidimensional nature compared with CFA, guiding clinicians to create a holistic management approach that address physical and psychosocial challenges. This preliminary study supports the use of ESEM in disability research, demonstrating its usefulness in identifying the multifaceted nature of LBP, therefore providing a broader perspective for assessment and management.
- MakaleYalnız künye2025Effects of high-protein nutritional supplementation on nutritional status, physical function, and quality of life in older gastric cancer patients receiving neoadjuvant chemotherapy: a randomized trial
Doğan Akagündüz, Diğdem; Türker, Perim Fatma; Akagündüz, Baran
Objectives: This study aimed to evaluate the effects of high-protein oral nutritional supplements (ONS) on nutritional status, physical function, and quality of life in older gastric cancer patients undergoing neoadjuvant chemotherapy (NAC). Methods: A prospective, randomized controlled trial was conducted between February 2023 and February 2024, including 46 patients aged 65 or older with newly diagnosed, locally advanced gastric cancer. Participants were randomized into two groups: an intervention group receiving high-protein ONS in addition to standard nutrition care, and a control group receiving only standard nutrition care. Nutritional status was assessed using the Mini Nutritional Assessment (MNA), physical function was evaluated through handgrip strength, Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) scales, and health-related quality of life was measured using the EORTC QLQ-C30. Bioelectrical impedance was used to analyze body composition. Results: Among the 46 patients (23 in each group), baseline characteristics were similar between the groups (p > 0.05). The ONS group showed significantly higher energy and protein intake than the control group (p < 0.05). MNA scores improved significantly in the ONS group after 8 weeks (p < 0.001), with a reduction in malnutrition risk to 4.3%, compared to 17.4% in the control group (p = 0.003). ADL and IADL scores remained stable in both groups, and both groups reduced functions and increased symptoms of HRQL over 8 weeks. Emotional functioning scores significantly declined in both groups over the 8-week period (ONS group: from 91.7 [16.67] to 83.3 [8.33], p = 0.001; non-ONS group: from 91.7 [8.33] to 83.3 [16.67], p = 0.011). Fatigue levels also increased markedly in both groups (ONS: from 11.1 [11.11] to 49.3 ± 17.02; non-ONS: from 22.2 [11.11] to 44.4 [22.22], p < 0.001). Additionally, constipation symptoms worsened significantly in the non-ONS group by week 8 (p = 0.008). Conclusions: High-protein ONS improved nutritional status and reduced malnutrition risk in older gastric cancer patients undergoing NAC. Further research is needed to assess the long-term effects of ONS on physical function and quality of life. Trial registration: Registered under ClinicalTrials.gov Identifier no. NCT06645912.
- MakaleAçık Erişim2025Optical coherence tomography angiography in non-alcoholic fatty liver disease: is it a disease affecting the microvascular system??
Tasli, Nurdan Gamze; Gunay, Betul Onal; Ugurlu, Adem; Eren, Mehtap Arslanturk; Aykut, Murat; Esenülkü, Cenap Mahmut
Purpose: To investigate retinal thickness and vascular structure in patients with non-alcoholic fatty liver disease (NAFLD) using optical coherence tomography (OCT) and OCT angiography (OCTA) and to compare the results with healthy controls. Method: The medical records of NAFLD patients were retrospectively reviewed. Macular thickness (MT) and peripapillary retinal nerve fibre layer (pRNFL) thickness were assessed. The vessel density (VD) of Superficial Capillary Plexus (SCP), Deep Capillary Plexus (DCP), foveal avascular zone (FAZ) area, FAZ circularity index (CI), and FAZ perimeter were also recorded. Results: The study included 64 patients with NAFLD and 64 healthy controls. Mean MT and pRNFLT were similar between groups. The study group showed a significant reduction in VD-DCP compared to the control group (36.0 ± 5.2 vs. 38.5 ± 4.1, p < 0.001). Total FAZ area was greater in the study group than in the control group (0.42 ± 0.10 vs. 0.33 ± 0.12mm2, p < 0.001). FAZ CI also differed between groups (0.47 ± 0.08 vs. 0.53 ± 0.08, p < 0.001). Enlarged FAZ area and decreased VD-DCP were significantly associated with NAFLD severity. Conclusion: Individuals with NAFLD have certain changes in the retinal microvasculature, including reduced VD-DCP, an increased FAZ area, and a decreased of FAZ CI. The variations in VD-DCP and FAZ area exhibit discrepancies according to the disease grade. There are some limitations, including its retrospective nature, the small number of participants, the lack of analysis of the peripapillary area, and the lack of examination of longitudinal changes.
- MakaleAçık Erişim2025Evaluation of Interleukin-10, Vascular Endothelial Growth Factor Levels, and Bone Marrow Parameters in Multiple Myeloma Patients at Diagnosis and After Treatment
Memis, Fulya; Kandefer, Meryem Yalvac; Aydin, Sonay; Dalva, Klara; Toprak, Selami Kocak
Background: Interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) are believed to possess a role in the pathophysiology of multiple myeloma (MM). We aimed to assess the significance of these parameters in the diagnosis, monitoring, and prognosis of the disease by examining them in patients at diagnosis and post-treatment and comparing the findings with those of healthy individuals. Methods: We conducted blood sampling from 35 patients diagnosed with MM at the time of diagnosis and from 15 of these patients post-treatment. We additionally assessed similar serum markers in a control group of 15 healthy individuals. Furthermore, we documented laboratory results, organ involvement, comorbidities, and CD27-CD81 levels assessed using flow cytometry in the bone marrow, along with treatments and patient responses. We also examined the quantity of cells collected during mobilization in patients who had autologous stem cell transplantation. Results: We found a positive correlation (p = 0.028/p = 0.035) between IL-10 and VEGF with the international staging score. In patients with renal involvement, IL-10 levels were higher and VEGF levels were lower than those without renal involvement (p = 0.011/p = 0.012). We showed that VEGF levels decreased significantly with treatment (p = 0.001). We found no statistically significant correlation between treatment responses and IL-10 and VEGF. The number of CD34 cells collected by mobilization showed a negative correlation with CD27 and a positive correlation with VEGF (p = 0.007/p = 0.032). Conclusions: Serum IL-10 level is associated with ISS and renal involvement in MM patients. There is a positive correlation between serum VEGF levels and the number of stem cells collected during mobilization. As CD27 expression increases, the number of stem cells collected in mobilization decreases.
- MakaleAçık Erişim2025Nobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activities
Atila Uslu, Gözde; Uslu, Hamit; Çoban, Taha Abdulkadir; Özkaraca, Mustafa; Mendil, Ali Sefa; Aygörmez, Serpil
Like other chemotherapeutic agents, 5-fluorouracil (5-FU) targets cancerous cells, but it also causes many unwanted side effects on healthy tissues and cells. Based on the undesirable effects of 5-FU, the aim of this study was to determine how 5-FU affects lung tissue and whether nobiletin has any protective effect. The study consisted of negative control, Nobiletin, 5-FU and Nobiletin + 5-FU groups. Nobiletin and Nobiletin + 5-FU groups received 10 mg/kg Nobiletin i.g. for 7 days. On day 8, 100 mg/kg 5-FU was administered i.p. to 5-FU and Nobiletin + 5-FU groups. Biochemical and immunohistochemical analyses were performed on the lung tissues dissected at the end of the study. 5-FU caused growth retardation, disturbed the oxidant-antioxidant balance by increasing MDA levels and decreasing GSH levels, triggered cellular apoptosis by increasing Bax and caspase-3 levels and decreasing Bcl-2, also increased lung tissue inflammation and damage by increasing NFκB and IL-1β levels. However, it was determined that Nobiletin prevented the disruption of the oxidant-antioxidant balance, showed significant anti-apoptotic effects, especially by reducing Bax levels and partially modulating caspase-3 and Bcl-2 levels, and also exhibited anti-inflammatory effects by reducing NFκB and IL-1β levels and supported the normal development of animals. Our results showed that nobiletin pretreatment showed anti-inflammatory activity by inhibiting the NFκB pathway in 5-FU-induced lung injury, suppressed oxidative stress with its antioxidant activity and was effective in modulating cellular apoptosis with its anti-apoptotic activity. In conclusion, Nobiletin has been shown to have an important potential in reducing fluorouracil-induced tissue damage by acting through multiple pathways.
