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A Fluorescent Aptasensor for Sensitive and Selective Determination of Epigenetic Cancer Biomarker N1-Methyladenosine in Urine Samples
(Wiley-V C H Verlag Gmbh, 2025) Bagda, Esra; Bagda, Efkan; Liu, Juewen
N1-methyladenosine (m1A) level in urine increases in the presence of cancer and is associated with the tumor size and stage. In the present study, we aimed to develop a method for rapid, sensitive and accurate determination of m1A in urine samples. The capture systematic evolution of ligands by exponential enrichment (SELEX) method was used to isolate aptamers that could selectively bind to m1A. We successfully isolated two sequences that have high selectivity toward m1A. The affinities against m1A were determined by isothermal titration calorimetry (ITC) and thioflavin T (ThT) assays. The N1MA1a aptamer has a Kd of 1.9 +/- 0.1 mu m determined by the ThT assay and 0.75 +/- 0.04 mu m determined by ITC. A strand-displacement biosensor was designed by labeling the aptamer with a carboxy fluorescein (FAM) and hybridizing it with a quencher-labeled complementary DNA strand. Using this biosensing system, m1A was detected with a detection limit of 1.9 mu m. The system shows high selectivity to m1A and high tolerance to adenosine, cytidine, guanosine, thymidine, uridine and N6-methyladenosine (m6A) as well as urine constituents at their real levels in urine. The sensor has been applied to five different human urine samples showing quantitative recovery values, which indicates practical potential of this aptamer-based biosensor.
The Effects of Sunitinib in Healthy and Cisplatin-Induced Rats
(Wiley-V C H Verlag Gmbh, 2023) Demirtas, Levent; Gurbuzel, Mehmet; Akbas, Emin Murat; Tahirler, Hilal; Karatas, Ozhan; Arslan, Yusuf Kemal
Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups - (1) control group (C) administered interperitoneally with a single dose 0.9 % saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1 beta and TGF-beta 3 expression levels when administered alone; it increased ALT, AST, and IL-38 levels. When sunitinib was given to the cisplatin-induced rats, it was observed that the increase in ALT, AST, and IL-38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.
New benzimidazole derivatives containing hydrazone group as anticancer agents: Inhibition of carbonic anhydrase IX and molecular docking studies
(Wiley-V C H Verlag Gmbh, 2025) Bostanci, Hayrani Eren; Yildiz, Mehmet Taha; Kapancik, Serkan; Inan, Zeynep Deniz Sahin; Kilic, Haci Ahmet; Guler, Ozen Ozensoy; Cevik, Ulviye Acar
In this study, we propose identifying potential novel compounds targeting carbonic anhydrase (CA) IX and anticancer activity. To study the impact of these synthesized compounds on CA IX and anticancer activity, we have developed and synthesized novel benzimidazole-hydrazone derivatives (3a-3j). The target compounds' H-1 NMR (nuclear magnetic resonance), C-13 NMR, and high resolution mass spectrometry spectra were used to confirm their chemical structures. L929 (healthy mouse fibroblast cell line) used as control healthy cell line and MCF-7 (breast cancer), C6 (rat glioblastoma), HT-29 (colon cancer), cells were used in cell culture studies. As a result of cell culture studies, it was determined that the newly synthesized compounds 3d and 3j had cytotoxic effects on colon cancer. Again, it was determined that the compound 3d had a more toxic effect than cisplatin on both breast cancer and glioma cells. According to the CA IX activity results, compounds 3d and 3j were found to have the highest activity. Compounds 3d and 3j are essential for having anti-cancer properties and inhibiting the carbonic anhydrase IX enzyme. Molecular docking of these compounds was carried out in the active site of CA IX. Flow cytometry and immunofluorescence microscope analyses also confirmed that these compounds had cytotoxic effects on cancer cells.
Benzothiazole Derived Ether Hybrids as Potent Anti-Thymidine Phosphorylase Agents: Synthesis, In Vitro, and Computational Investigations
(Wiley-V C H Verlag Gmbh, 2025) Usman, Muhammad; Alam, Aftab; Zainab; Khan, Majid; Tuezuen, Burak; Ayaz, Muhammad; Alanazi, Mohammed M.
This work is based on the synthesis of new ether derivatives bearing benzothiazole (BTA) scaffold through multistep reaction process. Initially, BTA was prepared by refluxing 4-hydroxybenzaldehyde with aminothiophenol having sodium metabisulfite in dimethylformamide (DMF); subsequently, the product was further refluxed with different substituted benzyl and alkyl bromides in acetone to get ether hybrids of BTA in good yields. Structurally, these compounds were confirmed by means of 1H, 13C-NMR, and mass spectrometry and evaluated for in vitro thymidine phosphorylase (TP) inhibitory activity. In the series, seven compounds attributed excellent inhibition against TP enzyme better than the standard. Similarly, three compounds showed good activity, whereas two compounds were found inactive. Moreover, all these compounds showed no toxicity to normal human fibroblast cell line (BJ cell line). In addition, Gaussian calculations were performed on the 6-31++g(d,p) basis set to examine the 13 synthesized compounds at the B3LYP, HF, and M062X levels. Additionally, molecular docking calculations were performed on TP enzyme proteins (PDB IDs: 4EAD, 2WK6, and 4LHM), and absorption, distribution, metabolism, excretion/toxicity (ADME/T) calculations were performed to investigate the effects and responses of these compounds in human metabolism.
Synthesis, Biological Activities, DFT Calculations, and Molecular Docking Studies of O-Methyl-Inositols
(Wiley-V C H Verlag Gmbh, 2025) Aksu, Kadir; Ayvaz, Melek col; Celik, Omer Faruk; Serdaroglu, Goncagul; Ustun, Elvan; Kelebekli, Latif
The concise synthesis of O-methyl-d-inositol derivative and conduritol derivatives was obtained starting from p-benzoquinone. Spectroscopic methods have been performed for the characterization of newly synthesized compounds. Cyclitols are useful molecules with anticancer, antibiotic, antinutrient, and antileukemic activities. Inositol class molecules, known as the most important cyclitol derivatives, were examined in this study for their 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide radical scavenging and butyrylcholinesterase (BChE) and glycosidase inhibition activities. It was observed that compound 5, in particular, showed efficacy that competed with the standards in terms of both antioxidant activity and enzyme inhibitor potential. Additionally, compound 5 shows effective antimicrobial activity. The water-soluble characteristics and lipophilic properties of the compounds were also considered and discussed. Moreover, the quantum chemical analyses were performed in light of the DFT/B3LYP/6-311G** level computations to elucidate/compare the studied inositols' possible reactivity directions. Additionally, the interactions of the molecules were analyzed against acetylcholinesterase (AChE), peroxiredoxin 5, and DNA gyrase by molecular docking methods. Cholinesterase inhibitors have an important status as the most important drug group used in the treatment of Alzheimer's disease today. Considering the effects of inhibition of the alpha-glucosidase enzyme by inhibitors, such molecules can also be used as therapeutic components in the treatment of diabetes.
Novel Aminothiazole-Chalcone Analogs: Synthesis, Evaluation Acetylcholinesterase Activity, In Silico Analysis
(Wiley-V C H Verlag Gmbh, 2025) Sarikaya, Meryem Kececi; Yildirim, Suheda; Kocyigit, Umit M.; Ceylan, Mustafa; Yirtici, Umit; Eyupoglu, Volkan
In this study, novel thiazole-chalcone analogs were synthesized, and their inhibitory effects on acetylcholinesterase (AChE) were examined. In vitro enzyme activity studies were conducted to calculate IC50 values, which were found to range between 2.55 and 72.78 mu M (tacrine IC50 = 53.31 mu M). The Ki values of the compounds showing the best inhibition (6g and 6e) were calculated and compared to those of the standard substance tacrine. All compounds reduced the AChE activity. Additionally, predictions made with SwissADME indicated that all compounds complied with Lipinski's rules and possessed good oral bioavailability properties, and the inhibitory effects of compounds 6e and 6g on AChE were evaluated using molecular docking and molecular dynamics simulations (100 ns). The results showed that compounds 6e and 6g had strong and stable interactions with AChE.
Research and product development for Crimean-Congo haemorrhagic fever: priorities for 2024-30
(Elsevier Sci Ltd, 2025) Semper, Amanda E.; Olver, Janie; Warner, Jenny; Cehovin, Ana; Fay, Petra C.; Hart, Peter J.; Golding, Josephine P.
Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed and potentially fatal tick-borne viral disease with no licensed specific treatments or vaccines. In 2019, WHO published an advanced draft of a research and development roadmap for CCHF that prioritised the development and deployment of the medical countermeasures most needed by CCHF-affected countries. This Personal View presents updated CCHF research and development priorities and is the product of broad consultation with a working group of 20 leading experts in 2023-24. The strategic goals, milestones, and timelines have been revised and expanded to reflect scientific advances since 2019, including the identification of antibodies with therapeutic potential and the progression of four vaccine candidates through phase 1 clinical trials. This update emphasises the need for a One Health approach to manage CCHF, from integrated crosssectoral surveillance to novel interventions that target ticks and their vertebrate hosts to reduce CCHF virus transmission to humans. The overarching vision for rapid diagnostics and specific therapeutics by 2028, followed by options to limit CCHF virus transmission and control disease by 2030, is deliberately ambitious and will only be achieved through coordinated international action from affected countries, funders, scientists, product developers, manufacturers, regulators, national authorities, and policy makers.
Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells
(Wiley-V C H Verlag Gmbh, 2025) Zoatier, Bayan; Yildiztekin, K. Gizem; Alagoz, M. Abdullah; Hepokur, Ceylan; Burmaoglu, Serdar; Algul, Oztekin
Type V MAPK inhibitors are distinguished by their capacity to target both the ATP binding site and a specific allosteric site on the enzyme. The present work utilized in silico analysis with Maestro 13.8.135 (Schrodinger) software in conjunction with experimental investigations to enhance the antiproliferative efficacy and forecast the likely mechanism of action of benzothiazole derivatives. Approximately 28 compounds were developed, produced, and assessed for their antiproliferative properties against two breast cancer cell lines: ER+ (MCF7) and ER- (MDA-MB-231), in addition to one normal mouse fibroblast cell line (L929). Their antiproliferative activities were evaluated via the MTT test, with doxorubicin and cisplatin serving as reference drugs for comparison. Consequently, the compounds with the greatest activity against the MCF7 cell line were chosen, and their inhibitory effects on the p38 alpha MAPK enzyme were examined. The molecular docking studies of compounds 15 and 19 demonstrated significant binding affinities for p38 alpha MAPK. Molecular dynamics simulations conducted over 100 ns revealed that compounds 15 and 19 exhibit stability inside both the ATP-binding domain and the lipid domain of p38 alpha MAPK. The research focused on creating effective Type V MAPK inhibitors demonstrate that compounds 15 and 19 possess considerable ability to inhibit p38 alpha MAPK, hence establishing them as promising anticancer agents.
Black Garlic Extract Modulates Endothelin Expression and Ovulatory Function in Monosodium Glutamate Treated Rats
(Wiley, 2025) Gezer, Arzu; Aras, Sukran Yediel; Ozkaraca, Mustafa; Baygutalp, Nurcan Kilic; Gundogdu, Gulhande; Sari, Ebru Karadag; Bedir, Gursel
Monosodium glutamate (MSG), a widely used food additive, has been associated with various health concerns, including potential reproductive toxicity. This study investigated the protective effects of black garlic (BG) ethanol extract against MSG-induced ovarian damage in rats. Thirty-two female rats in estrus were randomly divided into four groups (n = 8 per group): control (saline), BG (250 mg/kg BW), MSG (4 mg/g BW), and BG+MSG (combined treatment). Treatments were administered daily for 14 days. Ovarian tissues were collected for histopathological, immunohistochemical (IHC), and biochemical analyses. Histopathological examination revealed a significant reduction in cystic follicles in the BG+MSG group compared to the MSG group (p < 0.0001). IHC analysis showed decreased immunoreactivity of endothelin-1 and endothelin-2 in the BG+MSG group compared to the MSG group (both p < 0.01). Biochemical assays demonstrated significantly increased follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels in the BG+MSG group compared to the MSG group (all p < 0.05), while progesterone levels were significantly lower in the MSG group compared to the BG+MSG group (p < 0.05). These findings suggest that BG ethanol extract may mitigate MSG-induced ovarian dysfunction in rats by alleviating degenerative changes in follicles and modulating hormonal levels. This study provides insights into potential natural interventions for MSG-related reproductive toxicity.
Preserving Quality and Extending Shelf Life of Climacteric Persimmon Fruits Using Melatonin and Modified Atmosphere Packaging
(Wiley, 2025) Kucuker, Emine; Gundogdu, Muttalip; Guler, Emrah; Sumbul, Ahmet; Tekin, Onur; Hallac, Bulent
Quality and product losses during the postharvest storage of climacteric persimmon fruits pose significant challenges due to their short shelf life and limited marketing period. This study examined the effects of melatonin (1 mM) and modified atmosphere packaging (MAP) on preserving the quality, biochemical properties, and organic acid contents of persimmons, as well as extending their shelf life during storage at 0 degrees C +/- 0.5 degrees C. The MAP resulted in the lowest weight loss, recording only 6.63%. The combination of melatonin and MAP provided the highest fruit firmness at 8.69 kg/cm2, along with a total antioxidant level of 12.40 mu mol TE 100 g-1. Additionally, this treatment improved total phenolic content and most individual organic acids, except for fumaric acid, which was highest in the MAP treatment. The organic acid contents of the fruits varied during storage, depending on the specific acid. Malic acid was the predominant organic acid and was consistently better preserved by the treatments compared to the control. It is important to note that the reduction in malic acid was approximately 1.5 times less in the treated fruits than in the controls, while the decline of other organic acids was 3-4 times greater. In conclusion, both MAP and the combination of melatonin and MAP were effective methods for preserving the quality attributes and extending the shelf life of persimmon fruits.
Exploring free amino acid profiles in Crimean-Congo hemorrhagic fever patients: Implications for disease progression
(Wiley, 2024) Buyuktuna, Seyit Ali; Yerlitas, Serra Ilayda; Zararsiz, Gozde Ertuk; Dogan, Kubra; Kablan, Demet; Bagci, Gokhan; Ozer, Selda
This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus infection and alterations in amino acid metabolism. The primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.
Comprehensive evaluation of deep neck infections: A retrospective analysis of 111 cases
(Wiley, 2024) Aksoy, Ahmet; Demirkiran, Berat Baturay; Bora, Adem; Dogan, Mansur; Altuntas, Emine Elif
Purpose: Our study will analyze patients' clinical characteristics, treatment strategies, and complications with deep neck infection (DNI) using their medical records for five years. Methods: The present study included 111 patients diagnosed with DNI in our clinic between January 2018 and March 2023. The patients' complaints at admission, sociodemographic characteristics, season of diagnosis, findings from laboratory tests, radiological imaging performed at the time of first diagnosis, abscess localization, medical and surgical treatment methods used, and complications developing during follow-up were retrospectively examined. Results: The mean age of the patients included in the study was 38.51 +/- 16.92 (6-87 years). There was a significant correlation between chronic disease, smoking behaviours, oral hygiene, and DNI among patients based on their sociodemographic characteristics and medical history (p < .005). DNI development did not differ by season (p > .005). Physical examination findings predominantly revealed neck masses (39.6%) and peritonsillar abscesses (32.4%), and patients with peritonsillar abscesses had a shorter length of hospital stay than those with other localizations. No severe complications occurred during the clinical follow-up. Conclusion: Chronic diseases, smoking, and poor oral hygiene are the primary risk factors for developing DNIs. If an abscess is located in a critical area, it may require extended hospitalization and surgery under general anesthesia. Therefore, addressing these risk factors and encouraging good oral hygiene practices are crucial to preventing DNIs and reducing the need for intensive treatment.
Investigation of Long Noncoding RNA-NRAV and Long Noncoding RNA-Lethe Expression in Crimean-Congo Hemorrhagic Fever
(Wiley, 2024) Baysal, Aysenur Comez; Kiymaz, Yasemin cakir; Sahin, Nil Ozbilum; Bakir, Mehmet
Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic infectious disease caused by the CCHF virus, a member of the Bunyavirales order and the Orthonairoviridae family. The exact pathogenesis is not fully understood. Long noncoding RNAs (lncRNAs) are RNAs that are shown to play a role in various pathological processes of viral diseases. NRAV and Lethe are two well-known lncRNAs. Although previous studies have shown that NRAV and Lethe play important roles in the pathogenesis of viral infections, their role in CCHF is unknown. This study aimed to evaluate the expression levels of NRAV and Lethe in patients with CCHFV. Eighty patients diagnosed with CCHF were included, and RNA was extracted from their blood samples. The expression of NRAV and Lethe was measured using quantitative real-time polymerase chain reaction (qPCR). Patients were divided into three groups based on severity score, which was mild, moderate, and severe, and into two groups (survivors and non-survivors). The expression levels of NRAV and Lethe were compared between these groups. Of the patients, 49 (61.25%) were male, 31 (38.75%) were female, and the mean age was 38.62 +/- 19.28 years. No differences in age or gender were found between the groups. It was shown that NRAV expression was 21.86 times higher in the severe patient group compared to the moderate group and 22.74 times higher than in the mild group, statistically significant. When comparing fatal cases with survivors, NRAV expression levels were found to be 9.2 times higher in fatal cases. Lethe levels were 3 times lower in moderately severe cases compared to mild cases, but this difference was not statistically significant. In conclusion, our study suggests that NRAV may be a lncRNA involved in the pathogenesis of CCHFV.
SIRT2 deacetylates and decreases the expression of FOXM1 in colon cancer
(Wiley, 2024) Yildiz, Baris; Demirel, Ramazan; Staudacher, Jonas J.; Beseren, Hatice; Yildiz, Gulden; Akpinar, Ali Emre; Park, Seong-Hoon
New FOXM1-specific inhibitors with the potential to be used for therapeutic purposes are under extensive research. We hypothesized that deacetylation of FOXM1 would decrease protein expression, thus providing novel therapeutic management of colon cancers. Immunostaining was used to determine FOXM1 and SIRT2 expressions in human colon cancer tissue microarrays (n = 90) from Stage I to Stage IV. SIRT2-FOXM1 interaction was evaluated in colon cancer cells using immunoprecipitation. Deacetylation of FOXM1 via SIRT2 was determined using in vitro deacetylation assays. FOXM1 could be hyper-acetylated when p300 and pCAF histone acetyltransferases were administered alongside deacetylase inhibitors. We detected that SIRT2 and FOXM1 physically interacted, and SIRT2 deacetylated FOXM1 in vitro. SIRT2 overexpression led to a significant decrease while knockdown of SIRT2 increased the FOXM1 expression in HCT116 human colon carcinoma cells. In the analysis of 90 human colorectal cancer samples, high SIRT2 expression was observed in about 49% of colorectal cancer, intermediate in 29%, and low or no staining in 22%. Strong SIRT2 expression was found to be negatively associated with the FOXM1 staining in our clinical cohort. This study reveals a molecular interaction and association between SIRT2 and FOXM1 expression in colon cancer cell lines and human colon cancer samples, and suggests that targeting SIRT2 activity using small molecule modulators may be a promising therapeutic approach for colorectal cancer. SIRT2-FOXM1 interaction in colon cancer. SIRT2 and FOXM1 physically interacted and SIRT2 deacetylated FOXM1 in vitro. Strong SIRT2 expression was negatively associated with FOXM1 staining in a human colon carcinoma tissue microarray. Resveratrol, berberine, and quercetin reduced FOXM1 expression in colon cancer cells.image Upregulation of FOXM1 may be an early molecular signal required for cancer SIRT2 and FOXM1 physically interacted, and SIRT2 deacetylated FOXM1 in vitro Strong SIRT2 expression was negatively associated with the FOXM1 staining in the TMA Resveratrol, berberine and quercetin decreased FOXM1 expression in colorectal cancer cells
Differentiation of black tea according to country of origin using the μ-CTE/TD/GC-MS method combined with decision tree-optimizable neural network analysis
(Wiley, 2025) Okuyan, Nurullah; Yetim, Hasan; Kesmen, Zulal
BACKGROUNDAccurate discrimination of the country of origin of teas is critical to determine their actual commercial value, to meet consumer preferences, and to ensure compliance with labeling regulations. Therefore, in this study, we developed a new approach to accurately discriminate the country of origin of teas in the Turkish market.RESULTSA thermal desorption/gas chromatographic-mass spectrometric (TD/GC-MS) method combined with optimizable neural networks (ONN) was developed to analyze the volatile organic compounds (VOCs) of tea samples subjected to infusion or grinding pretreatments. Prior to GC-MS analysis, the conventional thermal desorption method was applied to VOCs in the powdered teas, while VOCs in the infused teas were adsorbed on Tenax-TA sorbent tubes attached to a micro-chamber/thermal extractor (mu-CTE) and then thermally desorbed. Using a feature selection technique, a total of 11 VOCs from infused tea samples, 21 VOCs from ground tea samples, and 18 VOCs from both groups were identified as specific VOCs that critically affect the classification of the teas. As a result of ONN classification of selected VOCs from only ground tea samples and infused tea samples, 95.51% and 96.7% accuracy was obtained, respectively, while 100% classification accuracy was achieved by ONN classification of VOCs from both sample groups.CONCLUSIONThe results showed that different pretreatments applied to Turkish and Ceylon teas caused the release of different volatile compounds, resulting in more specific VOC profiles. In addition, the developed mu-CTE/TD/GC-MS method allowed a more accurate classification of the black tea samples than the TD/GC-MS system alone. (c) 2025 Society of Chemical Industry.
Validity of a nutrition screening tool for childhood cancer
(Wiley, 2024) Kangalgil, Melda; Meral, Buket; Alford, Alexia J. Murphy; Erduran, Erol
BackgroundMalnutrition in pediatric oncology patients is a serious clinical condition. There is a need for standardized nutrition screening in pediatric oncology patients, as nutrition screening can offer a simple method to identify children with cancer at risk of malnutrition. This study aimed to determine the validity of a Turkish version of nutrition screening tool for childhood cancer (SCAN) in identifying the risk of malnutrition among children with cancer.Materials and MethodsA cross-sectional study was conducted with 78 children with cancer admitted to the pediatric hematology-oncology unit of a university hospital. In the first stage of this study, SCAN was translated into Turkish, and in the second stage, the validity of SCAN against pediatric Subjective Global Nutritional Assessment (SGNA) and Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition (AND/ASPEN) malnutrition criteria were evaluated.ResultsPatients had a median age of 8.0 years (range, 2-18 years; IQR, 5-14 years), 61.5% were male, and 60.3% were diagnosed with leukemia. According to SCAN, 53.8% had high risk of malnutrition. Validation of SCAN against pediatric SGNA showed that SCAN has a sensitivity of 97.5%, specificity of 94.5%, and accuracy of 96.1%.ConclusionThe risk of malnutrition is common in children with cancer. The Turkish version of the SCAN is a simple, quick, and valid tool to determine the risk of malnutrition in children with cancer. Further research is needed to understand the impact of nutrition interventions on clinical outcomes in children at risk for malnutrition based on SCAN.
Sulfonamide-Bearing Pyrazolone Derivatives as Multitarget Therapeutic Agents: Design, Synthesis, Characterization, Biological Evaluation, In Silico ADME/T Profiling and Molecular Docking Study
(John Wiley & Sons Ltd, 2025) Lolak, Nebih; Akocak, Suleyman; Topal, Meryem; Kocyigit, Umit Muhammet; Isik, Mesut; Turkes, Cuneyt; Topal, Fevzi
The research and design of new inhibitors for the treatment of diseases such as Alzheimer's disease and glaucoma through inhibition of cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and carbonic anhydrase enzymes are among the important targets. Here, a series of novel sulfonamide-bearing pyrazolone derivatives (1a-f and 2a-f) were successfully synthesized and characterized by using spectroscopic and analytical methods. The inhibitory activities of these newly synthesized compounds were evaluated both in vitro and in silico for their effect on carbonic anhydrases (hCA I and hCA II isoenzymes) and ChEs. The in vitro studies showed that these novel compounds demonstrated potential inhibitory activity, with K-I values covering the following ranges: 18.03 +/- 2.86-75.54 +/- 4.91 nM for hCA I, 24.84 +/- 1.57-85.42 +/- 6.60 nM for hCA II, 7.45 +/- 0.98-16.04 +/- 1.60 nM for AChE, and 34.78 +/- 5.88-135.70 +/- 17.39 nM for BChE. Additionally, many of these compounds showed promising inhibitory activity, and some showed higher potency than reference compounds. While the in silico studies have also identified the potential binding positions of these compounds, using the crystal structures of hCA I, II, AChE and BChE receptors. The varying affinities demonstrated by these designed compounds for ChEs and hCA isoenzymes show that these compounds could hold promise as potential alternative agents for selectively inhibiting ChEs and hCAs in the treatment of diseases such as Alzheimer's disease and glaucoma.
The role of radiotherapy in intracranial hemangiopericytoma/solitary fibrous tumors
(Springer Heidelberg, 2025) Kaydihan, Nuri; Yazici, Goezde; Erpolat, Petek; Kamer, Serra; Erdemci, Burak; Canyilmaz, Emine; Atasoy, Beste Melek
ObjectiveIntracranial hemangiopericytomas (HPC) are rare tumors. Radiotherapy (RT) is frequently performed after surgery, depending on tumor size, location, and the type of resection. Moreover, RT is preferred as an effective treatment for local recurrence and metastasis. With this multicenter study, we aimed to investigate the effectiveness of postoperative RT in intracranial HPC patients using modern RT techniques.Materials and methodsPatients aged 16 years and older who underwent RT for histologically confirmed intracranial HPC were evaluated retrospectively. Forty-four patients from 17 institutions were included. Demographic characteristics of the patients, pathological findings, and prognostic factors were documented. The Kaplan-Meier method was used for local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). The interval for survival analyses was calculated according to the end date of RT. Univariate and multivariate analysis methods were used for factors associated with survival and recurrence.ResultsMedian age was 42 years (16-71) and 70% of the patients were male. The most common initial symptoms were pain (47.7%) and vision problems (15.9%). A supratentorial location was observed in 79.5% of patients. The median maximum tumor dimension was 4.7 (1.6-14) cm. Gross total (GTR) and subtotal resection (STR) were performed in 43.2% and 47.7% of patients, respectively. Adjuvant RT commenced a median of 6 (2-16) weeks after surgery. Postoperative RT was administered using conventionally fractionated intensity-modulated radiotherapy (IMRT) or stereotactic radiosurgery (SRS). A total median dose of 60 (38-66) Gy in a median of 30 (19-33) fractions was used for patients treated with IMRT and a total median dose of 24 (12-25) Gy in a median of 3 (1-5) fractions was used for patients treated with SRS. Local recurrence occurred in 9 patients and locoregional recurrence in 2 patients at a median of 48 months (range 26-143 months) after RT. Reoperation and reirradiation were applied to 5 patients, reirradiation to 4 patients, and reoperation to 2 patients as salvage treatments. Reirradiation was administered at a median dose of 35 (13.5-54) Gy using a median of 5 (1-30) fractions. At a median follow-up of 63 (6-262) months, 5-year LC was 68.7%, DMFS 87.2%, PFS 60.8%, and OS 95.7%. The presence of residual macroscopic tumor before RT was associated with lower LC (p = 0.01) and shorter PFS (p = 0.04). In the presence of residual tumor before RT, 5-year LC decreased from 92.9% to 46.7%, while 5-year PFS decreased from 81.1% to 43.5% compared to patients with GTR. The presence of postoperative tumor was associated with a lower LC rate in Cox regression analyzes (p = 0.02). The hazard ratio was 6.2 (1.2-30). However, the effect of residual disease before RT on OS was not statistically significant.ConclusionAdjuvant radiotherapy is performed in the majority of patients with HPC, especially in cases where GTR cannot be performed. In our study, postoperative macroscopic residual tumor was found to be the only factor affecting LC and PFS in patients undergoing adjuvant RT, but its effect on OS was not shown. This may be due to the effectiveness of reoperation and/or reirradiation in the presence of recurrence after RT.
Investigation of the Presence of Papillomavirus in Bovine Testicles and Determination of γH2AX and Cytochrome C in Testicular Tissues Determined to be Infected
(Wiley, 2025) Karatas, Ozhan; Ozkaraca, Mustafa; Atasoy, Mustafa O.
This study aimed to detect the presence of bovine papillomavirus (BPV) in the testicular tissue of bulls over 1-year old by immunohistochemical, immunofluorescence and molecular assay targeting methods. In addition, gamma H2AX and cytochrome c expressions were evaluated by immunohistochemical and immunofluorescent methods in samples positive for BPV agent. In this study, 100 testicular specimens that did not show any macroscopic papilloma findings were collected. Testicular tissues were collected and examined using histologically and molecularly methods. In the present study, immunopositivity was detected in 6 (6%) samples with the IHC method and in 11 (11%) samples with the IF method. In addition, BPV positivity was detected in four (4%) samples by the PCR method and four (4%) samples determined to be BPV positive by PCR also showed immunopositivity in IHC and IF methods. gamma H2AX immunopositivity was seen in two of the BPV-positive samples by the IHC method, and gamma H2AX immunopositivity was observed in four of the samples determined to be positive for the BPV agent by the IF method. Cytochrome c immunopositivity was found in all the samples determined positive for the BPV agent. When the findings were evaluated, the presence of the BPV agent in the testicular tissues of cattle that did not have macroscopic papillomas was revealed for the first time. It was thought that the BPV agent caused double-stranded DNA breaks and increased cytochrome c expression.
In Vivo Evidence for the Preventive Role of Vaccinium macrocarpon Aiton in Indomethacin-Induced Gastric Ulcer: Focusing on Antioxidant, Anti-Inflammatory and Anti-Apoptotic Mechanisms
(Wiley, 2025) Aydin, Ismail Cagri; Ferah Okkay, Irmak; Okkay, Ufuk; Ozkaraca, Mustafa; Yesilyurt, Fatma; Yilmaz, Aysegul; Cicek, Betul
The present study aimed to unveil the gastroprotective potential of Vaccinium macrocarpon (VM) extract and its mechanism of action against indomethacin (INDO)-induced gastric ulcers in rats. To achieve this goal, rats were pretreated with either omeprazole (20 mg/kg) or VM (100 mg/kg) orally for 14 consecutive days. Gastric tissue samples were collected and various parameters were evaluated to understand the mechanism of VM's action, including the levels of superoxide dismutase, malondialdehyde, glutathione, CAT and transforming growth factor beta (TGF-beta), as well as the mRNA expression levels of tumour necrosis factor alpha, interleukin 1 beta, nuclear factor kappa B (NF-kappa B) and inhibitor kappa B (I kappa B). Additionally, the immunopositivity of cyclooxygenase (COX)-1, COX-2, PGE2, proliferating cell nuclear antigen (PCNA) and caspase-3 was assessed. The total amount of phenolic compounds present in the VM extract was high (58.08 mu g/mL gallic acid equivalent/mg extract). The healing effect of VM was demonstrated by an increase in the expression of PCNA. Furthermore, the level of TGF-beta was found to increase upon treatment with VM. Analyses of COX-1, COX-2 and PGE2 expression in gastric tissue confirmed the gastroprotective effect of VM. Notably, the expression of NF-kappa B was markedly reduced, whereas that of I kappa B was substantially increased. Overall, the findings of this study demonstrate that VM extract has gastroprotective and curative effects against INDO-induced ulcers through its antioxidant, anti-inflammatory, mucosal regenerative and anti-apoptotic activities. Therefore, VM may serve as a useful adjuvant treatment for nonsteroidal anti-inflammatory drugs-induced gastric ulcer disease.

Güncel Gönderiler