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
    Exploring the Potential of Lavandula stoechas in Smoking Cessation: A Molecular Docking Study of α4β2 Nicotinic Acetylcholine Receptor Interactions
    (Istanbul Univ, Fac Pharmacy, 2025-05-07) Barış, Elif; Portakal, Hüseyin Saygın
    Background: Lavandula stoechas, commonly known as lavender, has traditionally been used in various therapeutic applications, including smoking cessation. The molecular interaction of Lavandula stoechas compounds with the α4β2 nicotinic acetylcholine receptors, which are crucial for smoking cessation, is not well understood. This study aims to analyze these interactions and compare them with the known smoking cessation drug varenicline tartrate. Methods: Molecular docking analysis was performed on essential compounds of Lavandula stoechas to assess their binding affinities to the α4β2 nicotinic acetylcholine receptors. The study utilized the crystal structure of the receptor and conducted virtual drug screening using AutoDock Vina in the PyRx Virtual Screening Tool. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity profiles were also predicted using in silico methods. Results: The molecular docking revealed that several Lavandula stoechas compounds exhibited signif7 icant binding affinities to the α4β2 receptor. Compounds with the highest binding affinities were identified and compared with varenicline. The ADME and toxicity profiles indicated that these compounds had more favorable properties than varenicline, suggesting their potential as alternative smoking cessation agents. Discussion: The findings demonstrate that Lavandula stoechas contains compounds with significant binding affinities to the α4β2 nicotinic acetylcholine receptors, similar to varenicline. This indicates a potential role for Lavandula stoechas in smoking cessation therapy. The favorable ADME and toxicity profiles of these compounds further support their potential as alternatives to current smoking cessation drugs. This study paves the way for further research into the therapeutic applications of Lavandula stoechas in smoking cessation.
  • Article
    Aile Hekimlerinin Sağlıklı Yaşam Biçimi Davranışlarının ve Klinik Uygulamalarında Yaşam Biçimi Tıbbının Değerlendirilmesi
    (Galenos Publishing House, 2025-04-15) Semin, Ilgi; Kazdağlı, Hasan; Gökdemir, Özden; Semin, Makbule Ilgi
    Amaç: Bu çalışmanın amacı, aile hekimlerinin sağlıklı yaşam biçimi davranışlarını değerlendirmek ve klinik uygulamalarında yaşam biçimi tıbbına yönelik katılımlarını incelemektir. Yöntemler: Temmuz 2018 ile Ağustos 2019 tarihleri arasında aile hekimlerinden veri toplamak amacıyla çevrimiçi bir anket geliştirildi. Tanımlayıcı ve korelasyonel bir araştırma deseni kullanıldı. Çalışmada uygulanan anket, “katılımcıların kişisel bilgileri” ve “Sağlıklı Yaşam Biçimleri Davranış Ölçeği-II”i içermektedir. Kesitsel bir çalışma olarak tasarlanan bu araştırmada, örneklem kolayda örnekleme metodu ile sekiz ülkeden belirlenmiştir, ve anketler katılımcılara elektronik ortamda uygulanmıştır. Katılımcılara anketin süresi, veri saklama işlemleri, saklama süresi, araştırmacıların kimliği ve çalışmanın amacı hakkında bilgi verilmiştir. Bulgular: Çalışmaya 131 aile hekimi katılmış olup, erkek katılımcı oranı daha yüksek bulunmuştur. Sigara içme sıklığının Türk aile hekimleri arasında anlamlı derecede yüksek olduğu tespit edilmiştir (p=0,013). Ancak, ölçek toplam puanı veya altı boyutta alınan puanlar açısından aile hekimleri arasında istatistiksel olarak anlamlı bir fark bulunmamıştır. Sonuç: Çoğu aile hekimi, bu alanda daha fazla eğitim almak istediklerini belirtmiştir, bu da tıp fakültelerinin müfredatına eğitim müdahalelerin dahil edilmesi gerekliliğini göstermektedir. Ayrıca, iyi yapılandırılmış web tabanlı kitlesel çevrimiçi kurslar, aile hekimlerinin sağlıklı yaşam biçimi davranışları ve yaşam biçimi tıbbı uygulamalarına yönelik eğitim gereksinimlerini karşılamada etkili bir çözüm olabilir.
  • Article
    Prolonged Β-Hydroxybutyrate Ketosis Enhances Ponatinib Response of K562 Chronic Myeloid Leukaemia Cells
    (Dokuz Eylul Univ inst Health Sciences, 2025-01-31) Özkaya, Ali Burak; Geyik, Öykü Gönül; Malcanlı, Senanur
    Purpose: Ketosis is a metabolic state characterized by production of ketone bodies, including acetoacetate, β-hydroxybutyrate (BHB), and acetone, in response to reduced blood glucose levels. BHB stands out as the principal ketone body in nutritional ketosis which has diverse therapeutic implications for metabolic, nondegenerative and neoplastic disorders. In current study we investigated the impact of ketosis on chronic myeloid leukaemia (CML) cell viability and drug response. Materials and Methods: We investigated the impact of BHB-mediated ketosis on the viability of K562 cells, an in vitro model of CML, and explored the influence of BHB on the sensitivity of these cells to ponatinib, a multi-targeted tyrosine kinase inhibitor used in CML treatment. We used MTT assay to measure cell viability and Hoechst/PI assay to measure cell death. Results: Our findings reveal that BHB concentrations ranging from 1 mM to 5 mM, which fall within the physiological range of ketosis, elicit a minimal yet concentration-dependent reduction in cell viability. We also observed that while a 24-hour pre-treatment with BHB did not enhance the response of K562 cells to ponatinib, prolonged ketosis (4 days) improved response of cells to the drug by decreasing final cell viability from 25.15% to 13.12%. The primary mode of viability inhibition by ponatinib was cell death which was further intensified by exposure to prolonged ketosis. Conclusion: Ketosis induced by ketogenic diet of ketone body supplementation is considered as safe and effective adjuvant cancer therapy options and here, we report its potential effectiveness in the context of CML.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Right 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, Mustafa
    Objectives: 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: 1
    Citation - Scopus: 1
    Differential 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 Banu
    Objectives: 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 Akdogan
    Objectives 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.
  • Review
    Citation - WoS: 16
    Citation - Scopus: 40
    Current Evaluation and Recommendations for the Use of Artificial Intelligence Tools in Education
    (Walter De Gruyter Gmbh, 2023-12-01) Sagin, Ferhan Girgin; Özkaya, Ali Burak; Tengiz, Funda; Geyik, Öykü Gönül; Geyik, Caner
    This paper discusses the integration of artificial intelligence (AI) tools in education, delineating their potential to transform pedagogical practices alongside the challenges they present. Generative AI models like ChatGPT, had a disruptive impact on teaching and learning, due to their ability to create text, images, and sound, revolutionizing educational content creation and modification. However, nowadays the educational community is polarized, with some embracing AI for its accessibility and efficiency thus advocating it as an indispensable tool, while others cautioning against risks to academic integrity and intellectual development. This document is designed to raise awareness about AI tools and provide some examples of how they can be used to improve education and learning. From an educator's perspective, AI is an asset for curriculum development, course material preparation, instructional design and student assessment, while reducing bias and workload. For students, AI tools offer personalized learning experiences, timely feedback, and support in various academic activities. The Turkish Biochemical Society (TBS) Academy recommends educators to embrace and utilize AI tools to enhance educational processes, and engage in peer learning for better adaptation while maintaining a critical perspective on their utility and limitations. The transfer of AI knowledge and methods to the teaching experiences should complement and not replace the educator's creativity and critical thinking. The paper advocates for an informed embrace of AI, AI fluency among educators and students, ethical application of AI in academic settings, and continuous engagement with the evolving AI technologies, ensuring that AI tools are used to augment critical thinking and contribute positively to education and society.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in Aml Cell Lines With a Focus on Sphingolipids
    (Istanbul University Press, 2022-12-30) Yandım, Melis Kartal; Bilgin, Mesut
    Objective: Acute myeloid leukemia (AML) is a vigorous type of leukemia requiring effective treatment. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic molecule that is upregulated in AML and is studied as a target for treatment. The specific Mcl-1 inhibitor, S63845, has antiproliferative effects on AML cells. Bioactive sphingolipids have crucial roles in cells and regulate Mcl-1 stability. This study aimed to elucidate the changes in lipid profiles of AML cell lines in response to Mcl-1 inhibitor S63845 treatment, with a special focus on sphingolipids. Materials and Methods: The cytotoxic effects of S63845 were identified in the AML cell lines MV4-11, HL60, and KG1 using the MTT cell proliferation assay. Lipidome analysis was conducted by quantitative shotgun lipidomics covering 378 individual lipid species in 26 classes within the major lipid categories. Results: The IC50 values of S63845 have been calculated as 7 nM for MV4-11, 53 nM for HL60, and 479 nM for KG1. The lipidome results reveal the S63845 treatment to increase ceramide (Cer) levels in the MV4-11 and KG1 cell lines at the expense of downstream sphingolipids while increasing the hexosylceramide (HexCer) levels in the HL60 cell line at the expense of the Cer and sphingomyelin (SM). Conclusion: This study showed S63845 to be able to suppress cell proliferation by altering lipid compositions in AML cell lines. More importantly, the study suggested S63845 to differentially affect the lipid profiles of AML cell lines.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 3
    Effects of Kynurenic Acid and Choline on Lipopolysaccharide-Induced Cyclooxygenase Pathway
    (Walter De Gruyter Gmbh, 2023-06-01) Barış, Elif; Şimşek, Oguzhan; Uysal Yoca, Özge; Demir, Ayşe Banu; Tosun, Metiner; Yoca, Ozge Uysal
    Objectives: Inflammation can be endogenously modulated by the cholinergic anti-inflammatory pathway via calcium (Ca2+)-permeable alpha-7 nicotinic acetylcholine receptor (a7nAChR) ion channel expressed in immune cells. a7nAChR agonist choline and tryptophan metabolite kynurenic acid (KYNA) produces immunomodulatory effects. This study aimed to determine the effects of the choline and KYNA on the lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 pathway.Methods: In vitro inflammation model was produced via LPS administration in macrophage cells. To determine the effective concentrations, choline and KYNA were applied with increasing concentrations and LPS-induced inflammatory parameters investigated. The involvement of nAChR mediated effects was investigated with the use of non-selective nAChR and selective a7nAChR antagonists. The effects of choline and KYNA on COX-2 enzyme, PGE(2), TNFa, NF-?B and intracellular Ca2+ levels were analyzed.Results: LPS-induced COX-2 expression, PGE(2) TNFa and NF-?B levels were decreased with choline treatment while intracellular calcium levels via a7nAChRs increased. KYNA also showed an anti-inflammatory effect on the same parameters. Additionally, KYNA administration increased the effectiveness of choline on these inflammatory mediators.Conclusions: Our data suggest a possible interaction between the kynurenine pathway and the cholinergic system on the modulation of LPS-induced inflammatory response in macrophages.
  • Article
    Hepatit C Virusunun Genomik Varyasyonları ve Kliniğe Etkileri
    (2015) Abacıoğlu, Yusuf Hakan; Ergünay, Koray
    Hepatit C virusu (HCV), tüm dünyada yaygın olarak bulunan, 110 milyonu aşkın kişiyi enfekte etmiş, ciddi bir halk sağlığı tehdidi oluşturan kronik hepatit etkenidir. Maruziyetin ardından, kronik hastalık riski yüksek olan ve koruyucu bir aşısı bulunmayan HCV; siroz, transplantasyon gerektiren karaciğer yetmezliği ve hepatoselüler karsinomun önde gelen enfeksiyöz etkenleri arasında yer almaktadır. Replikasyon mekanizmaları ve konaktaki enfeksiyon dinamikleri nedeniyle, virus, enfekte kişilerde türümsüler (quasispecies) olarak tanımlanan, birbirine çok benzer genetik varyantları içeren bir popülasyon halinde bulunur. HCV enfeksiyonlarında patogenez ve hastalığın ilerleyişi, virusa ait genetik çeşitlilik ve türümsü kompozisyonlarında izlenen değişikliklerle doğrudan ilgilidir. Virus, yüksek düzey çeşitlilik gösteren varyant havuzundan, iç ya da dış kaynaklı seçici baskıların varlığında replikasyonunu sürdürebilecek mutantların oluşumu ile, hastalık patogenezini devam ettirir. Enfeksiyon süresince, türümsüler birçok değişikliğe uğrar ve konağın hümoral ve hücresel yanıtından kaçan mutantlar, antiviral tedaviye karşı da dirençli mutantların oluşumu için zemin hazırlar. Yeni jenerasyon dizileme tekniklerinin de katkısıyla, HCV'nin kökeni ve epidemiyolojisi, ayrıca hastalık süreçlerinde izlenen genomik çeşitlilik üzerine birçok güncel bilgi elde edilmiştir. Bu derlemede, HCV'nin genetik çeşitliliğini oluşturan temel mekanizmalar ve klinik gidişle bağlantılı olarak konakla olan etkileşimler; virus ve konak yönünden hümoral ve hücresel immün yanıt, enfeksiyonun erken ve geç dönemlerindeki değişiklikler ve kronik enfeksiyona ilerleme süreci açılarından ele alınmaktadır. Ek olarak virus epidemiyolojisi ve moleküler evrimi üzerine güncel bulgular, türler arası ve popülasyon perspektifl erinden yorumlanmaktadır. Doğrudan etkili antivirallere dayalı rejimlerin uygulamaya girdiği günümüzde, genetik varyasyonlar ve tedaviye direnç ile ilişkileri, güncel saptama yöntemleri de özetlenerek tartışılmaktadır