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 Upregulated Acute Systemic Inflammation-Related Genes Based on Endotoxin Exposure Provide ‘Survival Benefit’ or Create ‘High Risk of Death’ in Leukaemia and Colon Cancer(Istanbul University, 2024-07-10) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem Ayna; Ayna Duran, GizemObjective: Although endotoxin exposure has been shown to trigger innate immune responses and promote cancer, it has also been shown to prevent cancer formation. In our study, survival analysis was performed to determine whether the upregulated genes triggered by endotoxins have hazardous effects on cancers or provide a survival benefit. Materials and Methods: Gene intensity values of control and bacterial endotoxin-administered individuals were obtained from the Gene Expression Omnibus database. Using the R "Linear Models for Microarray Data" package, differentially expressed gene analyses were conducted to determine genes that differ between healthy and bacterial endotoxin-administered samples. "ShinyGo 0.80" web-based tool was used to determine the disease types indicated by these genes. The "Kaplan-Meier Plotter" web-based tool was used to conduct survival analysis. Results: Genes that create an innate immune response to bacterial endotoxin exposure and are upregulated differently than in individuals without exposure were identified. According to gene enrichment analyses, the two main types of cancer identified were leukaemia/lymoma and colon cancer. We detected that MLF1, STAT5B, and BCL3 genes led to poor survival; however, the ARHGAP26 gene was protective for acute myeloid leukaemia patients. In the case of colon cancer, SMAD7 and TLR2 genes were determined as leading to "high risk of death". Conclusion: Once the systemic inflammation-related genes identified in our study are confirmed through laboratory experiments in samples taken from solid tissue in the case of colon cancer and at the level of genes obtained from blood samples in leukemias, genetically targeted treatments will also be possible.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 Expressions of the Satellite Repeat Hsat5 and Transposable Elements Are Implicated in Disease Progression and Survival in Glioma(Tubitak Scientific & Technological Research Council Turkey, 2024-08-23) Köse, Sıla Naz; Yaraş, Tutku; Bursalı, Ahmet; Oktay, Yavuz; Yandım, Cihangir; Karakulah, GökhanThe glioma genome encompasses a complex array of dysregulatory events, presenting a formidable challenge in managing this devastating disease. Despite the widespread distribution of repeat and transposable elements across the human genome, their involvement in glioma's molecular pathology and patient survival remains largely unexplored. In this study, we aimed to characterize the links between the expressions of repeat/transposable elements with disease progression and survival in glioma patients. Hence, we analyzed the expression levels of satellite repeats and transposons along with genes in low-grade glioma (LGG) and high-grade glioma (HGG). Endogenous transposable elements LTR5 and HERV_a-int exhibited higher expression in HGG patients, along with immune response-related genes. Altogether, 16 transposable elements were associated with slower progression of disease in LGG patients. Conversely, 22 transposons and the HSAT5 satellite repeat were linked to a shorter event-free survival in HGG patients. Intriguingly, our weighted gene coexpression network analysis (WGCNA) disclosed that the HSAT5 satellite repeat resided in the same module network with genes implicated in chromosome segregation and nuclear division; potentially hinting at its contribution to disease pathogenesis. Collectively, we report for the first time that repeat and/or transposon expression could be related to disease progression and survival in glioma. The expressions of these elements seem to exert a protective effect during LGG-to-HGG progression, whereas they could have a detrimental impact once HGG is established. The results presented herein could serve as a foundation for further experimental work aimed at elucidating the molecular regulation of glioma genome.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 In Silico Approach for Identification of PI3K/MTOR Dual Inhibitors for Multiple Myeloma Treatment(Istanbul Univ, 2023-04-14) Masalaci, Ilke; Akdogan, Yaren; Mutlu, Ozge; Eyvaz, Hande; Kiraz, YagmurObjective: Multiple myeloma is a hematologic malignancy in which targeting phosphoinositide 3 kinase (PI3K) and/or the mammalian target of rapamycin (mTOR) individually has been shown to have anti-proliferative effects, however, inhibiting both proteins simultaneously has been reported to have more effective results for its treatment. The aim of this study is to determine the molecular interactions and predicted inhibitory effects of 40 different dual inhibitors on mTOR, PI3K delta, and PI3K gamma to propose potentially the most effective dual inhibitor that targets the PI3K delta and PI3K gamma isoforms as well as the mTOR proteins since those isoforms are known to be predominant in multiple myeloma patients. Therefore, the focus in this study is built around the specific targeting of the PI3K delta and PI3K gamma isoforms from the multiple myeloma perspective. Materials and Methods: In silico docking experiments were conducted to determine the binding energies for different ligands that target mTOR, PI3K delta, and PI3K gamma. Protein-dual inhibitor complexes and the amino acids and bond types were visualized to identify molecular interactions. The absorption, distribution, metabolism, and excretion properties of dual inhibitors were analyzed and evaluated. Results: The binding affinity values were found to be between -7 and -9.9 kcal/mol. The toxicity prediction values of the selected dual inhibitors were obtained from the Pro-Tox-II web tool and classified according to the globally harmonized system of classification of labeling of chemicals. Conclusion: Correspondingly, among all dual inhibitors, Vistusertib is determined to be a promising compound against multiple myeloma cells by inhibiting both PI3K delta and PI3K gamma as well as mTORC1/2.