TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article HR-LCMS Based Metabolite Profiling of Methanolic Leaf Extract of Terminalia Pallida Brandis and Its Antioxidant Potential(2025-04-08) Guguloth, Dr. Sarvan KumarTerminalia species are being reported as medicinally useful. Terminalia pallida Brandis is one of the plants of the family Combretaceae. The aim of the present study is to catalog the phytochemical distribution and to validate the antioxidant potential of methanolic leaf extract (METP). Antioxidant potential of methanolic leaf extract was estimated by DPPH assay and phytochemical distribution was assessed by HR-LCMS analysis. The antioxidant test result of leaf extract displayed a potential free radical scavenging effect at test concentrations (p<0.001). In HR-LC-MS study a total of 29 bioactive compounds of a variety of chemical classes like flavanoids, alkaloids, fatty acids, diterpenoids, glycosides, amino acids and polyphenols etc were identified in both positive & negative ion mode, and among these few compounds possessed various biological activities. Based on these obtained results, it is concluded that METP constitute 29 bioactive compounds and possess potential antioxidant property in concentration dependent manner.Article Virtual Drug Screening Study to Discover Novel ERAP1 Allosteric Site Inhibitors for the Treatment of Ankylosing Spondylitis (AS)(Marmara Univ, Fac Pharmacy, 2025-04-08) Portakal, Hüseyin Saygın; Alp, Beste; Akyol, MertcanEndoplasmic reticulum aminopeptidase 1 (ERAP1) is one of the key molecules in the antigen presentation process. To date, associations of ERAP1 with Ankylosing Spondylitis (AS) have been revealed with strong data. As such, to target the allosteric site of ERAP1 exhibits a therapeutic potential in the treatment of AS. In this paper, 9,800 ligands from “FDA-Approved Drugs'', “World-not-FDA Approved Drugs'', and “Drugs in Clinical Trials'' datasets of ZINC15 database were screened to the allosteric site of ERAP1. The best scored drugs are filtered with ADME analysis, the toxicity and bioactivity profiles of the discovered drugs and the known inhibitors were investigated. Results revealed that ZINC000100052688 (Ventavis), ZINC000004217466, and ZINC000024760115 (Dactolicib) follow the Lipinski’s rule of five and have -10.0 kcal/mole, -9.8 kcal/mole, and -9.7 kcal/mole binding affinities to allosteric site of ERAP1, respectively. Furthermore, ZINC000004217466 is the most promising since it has high protease and enzyme inhibitory activity with no toxicity. Due to that to date, only few chemical ligands recognizing ERAP1 regulatory site have been synthesized, to reveal possible repurposable drugs is quite promising, and ZINC000004217466 is the best candidate among 9,800 drugs since it has rather binding affinity, proper chemical properties, no toxicity, and high bioactivity in the inhibition of ERAP1 regulatory site.Article Bioinformatics Based Drug Repurposing Approach for Breast and Gynecological Cancers: RECQL4/FAM13C Genes Address Common Hub Genes and Drugs(Galenos Publ House, 2025-01-02) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem AynaObjective: The prevalence of breast cancer and gynaecological cancers is high, and these cancer types can occur consecutively as secondary cancers. The aim of our study is to determine the genes commonly expressed in these cancers and to identify the common hub genes and drug components. Materials and Methods: Gene intensity values of breast cancer, gynaecological cancers such as cervical, ovarian and endometrial cancers were used from the Gene Expression Omnibus database Affymetrix Human Genome U133 Plus 2.0 Array project. Using the linear modelling method included in the R LIMMA package, genes that differ between healthy individuals and cancer patients were identified. Hub genes were determined using cytoHubba in Cytoscape program. “ShinyGo 0.80” tool was used to determine the disease-specific biological KEGG pathways. Drug.MATADOR from the ShinyGo 0.80 tool was used to predict drug-target relationships. Results: The RecQ Like Helicase 4 and Family with Sequence Similarity 13 Member C genes were found to be similarly expressed in breast cancer and gynaecological cancers. Upon KEGG pathway analyses with hub genes, Drug.MATADOR analysis with hub genes related to cancer related pathways was performed. We have determined these gene/drug interactions: NBN (targeted by Hydroxyurea), EP300 (targeted by Acetylcarnitine) and MAPK14 (targeted by Salicylate and Dibutyryl cyclic AMP). Conclusion: The drugs associated with hub genes determined in our study are not routinely used in cancer treatment. Our study offers the opportunity to identify the target genes of drugs used in breast and gynaecological cancers with the drug repurposing approach.Article Citation - WoS: 1Citation - Scopus: 125-Hydroxyvitamin Levels in Sjögren’s Syndrome: Is It the Right Time to Dismiss the Case or Not(Walter de Gruyter GmbH, 2024-09-23) Sımsır, Ilgın Yıldırım; Tanigor, Goksel; Karabulut, Gonca; Barutcuoglu, Burcu; Yılmaz, ZevcetObjectives: This study aimed to investigate whether patients with primary Sjögren syndrome (SjS) have different levels of 25 OH-D3 (vitamin D) when compared to healthy populations and whether differences in 25 OH-D3 correlated with disease activity or markers. Methods: Eighty-eight female patients with SjS and 3,338 age-matched healthy female controls were included in this study. 25 OH-D3 levels were compared with healthy controls. Then the patients were stratified according to their 25 OH-D3 levels, either insufficient/deficient or normal (<50 nmol/L or ≥50 nmol/L). The disease activity was evaluated using The EULAR SjS disease activity index (ESSDAI) and its components. Correlation analyses were also performed for a possible correlation with disease characteristics and markers of activity. Results: No differences in 25 OH-D3 levels were found between SjS and healthy populations (p>0.05). No correla- tions were found between patient characteristics or labo- ratory values (p>0.05). Conclusions: This study did not find a link between disease characteristics and disease activity and 25 OH-D3 levels. Prospective studies with more patients should be conducted to reach a conclusion.Article Citation - WoS: 2Citation - Scopus: 2Right Vagotomy Alters Heart Rate Variability Temporarily and Increases Total Choline Levels in Rats(Walter de Gruyter GmbH, 2024-07-01) Barış, Elif; Ozel, Hasan Fehmı; Kazdağlı, Hasan; Özbek, MustafaObjectives: The variability in the time intervals between heartbeats, known as heart rate variability (HRV), serves as a reflection of the intricate interplay between the sympathetic and parasympathetic neural systems. While the potential asymmetric effects of the left and right branches of the vagus nerve remain uncertain, this study aims to investigate the impact of unilateral, bilateral, and atropine interventions on HRV parameters and choline levels within cardiac tissue. Methods: 40 male adult Wistar albino rats were randomly assigned to the five groups (each n=8): sham-operated, atropine, right vagotomy, left vagotomy, and bilateral vagotomy. Heart rate variability (HRV) analyses were conducted, and the levels of total choline/acetylcholine in heart tissues were quantified. Statistical analyses were performed to assess the results. Results: The bilateral vagotomy and atropine groups exhibited higher heart rates and high frequency power (HF), along with reduced low frequency power (LF). Total power (TP) remained relatively unchanged. In the bilateral vagot- omy group, DFAα1 was significantly elevated while DFAα2 was reduced significantly. SD1 and SampEn were significantly lower in both the bilateral vagotomy and atropine groups. Notably, the right vagotomy group displayed significant changes primarily in the 15th minute, particularly in time- domain parameters, HF, TP, and SD1, with a significant in- crease observed in total choline levels. Conclusions: Our results revealed that asymmetrical vagal innervation induces distinct effects on heart rate variability parameters and total choline/acetylcholine levels in heart tissues. Our findings suggest that compensatory hemody- namic recovery, possibly driven by contralateral vagal overactivity, may contribute to these observed results.Article Citation - WoS: 1Citation - Scopus: 1Differential Effects of Choline on TLR2/4 Mediated Signaling Through Possible Regulation of Toll-Interacting Protein in Hepatocellular Carcinoma Cell Lines(Walter de Gruyter GmbH, 2024-05-30) Barış, Elif; Demir, Ayse BanuObjectives: Toll-like receptor (TLR) mediated inflammatory status plays an important role in development and pro- gression of hepatocellular carcinoma (HCC). Toll-interacting protein (TOLLIP) has an inhibitory effect on TLR-mediated inflammatory signalling and expression profile of TOLLIP varies between malignancies including HCC. Cholinergic anti-inflammatory pathway (CAP) is an endogenous mech- anism that controls inflammatory status via α7nicotinic acetylcholine receptors (α7nAChR). This study aims to investigate the effect of CAP-acting agent choline on TOLLIP and its related TLR-mediated inflammatory response in HCC cells with distinct differentiation stages. Methods: The expression patterns of α7nAChR, TLR2/4, TOLLIP, IL6, NFkB genes were evaluated by RT-PCR and ELISA in the presence of choline, along with the real-time cell proliferation and migration in HEP3B and SNU449 HCC cell lines. The interaction between choline and TOLLIP assessed by using in-silico analyses. Results: Choline downregulated TOLLIP in Hep3B and SNU449 cells. However, the expressions of α7nAChR, NF-κB, IL-6, TLR2 and TLR4 showed a decreased pattern in well differentiated HEP3B cells, while an increased pattern in poorly differentiated SNU449 cells. Conclusions: Choline might exert differential effects in TLR2/4-dependent signalling based on the differentiation stages of the HCC cells, suggesting its potential therapeutic effects in earlier stages of HCC which might be result of its partial modulation of TOLLIP.Article Identification of the Role of Tg2 on the Expression of Tgf-Β, Timp-1 and Timp-2 in Aged Skin(Walter De Gruyter Gmbh, 2024-02-12) Ergülen, Elvan; Akdoğan, Gül; Guner, Gul AkdoganObjectives Transglutaminase 2 (TG2) is a unique protein having enzymatic and nonenzymatic functions that have been implicated in various biological and pathological processes such as cell survival and apoptosis, cell signaling, differentiation, adhesion and migration, wound healing and inflammation. As reported in previous studies, TG2 expression and activity increase by age suggesting that TG2 possibly has roles in cellular aging process. In this study, we aimed to explore the role of TG2 in chronological skin aging through its impact on the expression of some important extracellular matrix (ECM) proteins including TGF-beta, TIMP-1 and TIMP-2. Methods We have compared TG2 expression and activity in young and in vitro chronologically aged human dermal fibroblasts via Western blot and in situ TG2 activity assays. Afterwards, we inhibited TG2 expression via siRNA transfection and activity via active site inhibitor of TG2 separately in aged dermal fibroblasts and monitored the expression levels of TGF-beta, TIMP-1 and TIMP-2 in these cells by Western blot and compared to that of untreated control cells. Results We obtained evidence that both TG2 expression and activity increase in aged cells. However, protein levels of TGF-beta, TIMP-1 and TIMP-2 do not exhibit any significant difference in TG2 downregulated or TG2 activity inhibited aged cells compared to control cells. Conclusions Our results indicate that changes in the expression and activity of TG2 in (in vitro) chronologically aged human dermal fibroblasts do not impact the expression patterns of TGF-beta, TIMP-1 and TIMP-2 proteins.Article Exploring Pi3k Pathway Inhibitors for Acute Myeloid Leukemia: a Drug-Repurposing Approach(Istanbul University Press, 2023-12-28) Ergun, Cansu; Kiremitci, Buse Zeren; Arslantas, Gizem; Bozkurt, Busenur; Duran, Gizem Ayna; Kiraz, YağmurObjective: Acute myeloid leukemia (AML) is a malignant disease characterized by the uncontrolled growth, differentiation, and proliferation of immature hematopoietic cells. Patients with AML often have poor survival rates, which are associated with specific gene mutations in FLT3, CEBPA, and NPM1. The phosphatidylinositol 3-kinase (PI3K) pathway, a lipase pathway, is activated in many malignancies, including AML. Given the low survival rates in AML, this study identified candidate drugs that could inhibit the PI3K pathway, thereby offering a potential treatment for AML, by using a drug-repurposing approach. Materials and Methods: Online bioinformatics tools were utilized to identify pathway-related genes and FDA-approved drugs. Subsequently, molecular docking was performed to determine the binding affinity values. Important genes were identified by evaluating their impact on survival and their aberrant expression in the tumor. In this study, genes such as VAV1, GSK3B, MTOR, PDPK1, PRR5, TSC2, AKT3, and CREB1 were determined and docked with their potential inhibitors. Particular attention was paid to VAV1 because there were no known potential VAV1 inhibitors used in AML. Results: The docking results were ranked, and the proposed gene–drug pairs were identified as tideglusib and fostamatinib for the inhibition of GSK3B, pimecrolimus and fostamatinib for the inhibition of MTOR, and fostamatinib for the inhibition of PDPK1. Furthermore, nebivolol, darifenacin, dihydroergotamine, libanserin and entereg were identified as potential inhibitors of VAV1 in AML. Conclusion: To sum up, most effective gene–drug pairs according to binding affinities were proposed as candidate inhibitor drugs for AML.Article Cardiac Functions and Peripheral Arterial Stiffness in Patients With Polycystic Ovary Syndrome: a Cross-Sectional Study(Galenos Publ House, 2023-08-01) Colak, Ayse; Ozpelit, Mehmet Emre; Okyay, Emre; Kumral, Zeynep; Özpelit, Ebru; Okyay, Recep EmreBACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) patients have been described as having subclinical cardiac and vascular damage; nevertheless, research data is contradictory. We aimed to assess global cardiac functions, peripheral arterial stiffness (AS), and the relationships between echocardiographic and AS measurements in patients with PCOS. MATERIALS AND METHODS: We enrolled 42 consecutive PCOS patients and 32 age- and body mass index (BMI)-matched healthy controls. All participants underwent a comprehensive two-dimensional echocardiographic examination. Applanation tonometry was utilized to determine peripheral AS [carotid-radial pulse wave velocity (PWV) and augmentation index (AIx)] in each participant. In addition, we evaluated the correlation between AS and echocardiographic parameters. RESULTS: The PCOS and control groups had similar ages and BMIs. Right ventricular (RV) and left ventricular (LV) diameters, LV mass, and LV ejection fraction were similar between the groups. Considering the pulse wave and tissue Doppler parameters of the cardiac functions, the LV septal S’, LV Tei index, RV S’, RV Tei index, and E/E’ ratio were comparable between the two groups. Peripheral AS parameters including, PWV and AIx were higher in those patients with PCOS [19.3±12.5 vs. 12.5±9.6; p=0.01 and 5 (4.7-5.5) vs. 4.4 (4.2-4.8); p=0.0001, respectively]. AS parameters were not correlated with echocardiographic parameters. CONCLUSION: Despite normal echocardiographic LV and RV functions, women with PCOS had increased AS. There was no correlation between echocardiographic and AS parameters in these patients.Article A Novel Molecular Indicator for Inhibitor Development in Haemophilia A(Galenos Publishing House, 2021-05-25) Işık, E.; Mehdiyeva, H.; Akgün, B.; Köse, T.; Kavaklı, K.; Özkınay, F.; Atik, T.Aim: Previous studies have reported inhibitor development (ID) risk in those patients who have hemophilia A (HA) with missense mutations to be 3-10%. We investigated the association between ID risk and various features of missense mutations; including the impact directly related to amino acid group change. Materials and Methods: Missense mutations in the F8 gene, clinical findings of the patients including severity of HA, and ID status were obtained from the F8 gene variant database (http://www.factorviii-db.org/). Twenty amino acids were then classified into groups according to their side chains. All information regarding each specific mutation, as well as any impact of the mutation on the amino acid group change, was recorded. Additionally, localization (at which domain) of any changed amino acid in the F8 protein was noted. Combined Annotation Dependent Depletion (CADD), Rare Exome Variant Ensemble Learner (REVEL), Mendelian Clinically Applicable Pathogenicity and Deleterious Annotation using Neural Networks scores were applied to identify a significant cut-off value indicative of ID. Results: Three variations were identified that could be considered as useful in the prediction of ID in mild HA. The first being that among mild HA patients, 7.9% (n=70/883) with mutations causing no amino acid group changes showed ID. This rate, however, was only 2.9% in patients with mutations leading to amino acid group changes. Secondly; in patients with mutations causing no amino acid group changes affecting A2, A3 and C2 domains, ID risk was found to be higher than in patients with mutations leading to amino acid group changes. Thirdly; an association between ID and CADD and REVEL scores was observed. Conclusion: In mild HA patients, the characteristics of missense mutations in terms of amino acid group changes, and CADD and REVEL scores could be of considerable utility in the prediction of ID risk. © Copyright 2021 by Ege University Faculty of Medicine, Department of Pediatrics and Ege Children’s Foundation