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Öğe Application of ultrasound to the organic cornelian cherry (Cornus mas L.) vinegar: Changes in antibacterial, antidiabetic, antihypertensive, and anticancer activities(Wiley, 2022) Erdal, Berna; Akalın, Ramadan Bilgin; Yılmaz, Bahar; Bozgeyik, Esra; Yıkmış, SeydiIn this study, to determine their alternative/complementary properties, organic cornelian cherry vinegar samples prepared by traditional (CCV), thermal pasteurization (P-CCV), and ultrasound (UT-CCV) methods were tested for antibacterial, antidiabetic, antihypertensive, and anticancer activities. As a result of response surface methodology optimization, the bioactive compounds were increased. With ultrasound treatment, the total phenolic content increased by 4.6%. The antibacterial activity was detected in all samples, while the lowest MIC values (28.4 mu l/ml) in the presence of UT-CCV were found in Pseudomonas aeruginosa, Klebsiella pneumoniae, Bacillus cereus, and Staphylococcus aureus. In addition, apoptosis was induced in HT-29 and MDA-MB-231 cells were treated with the CCV, P-CCV, and UT-CCV samples compared to the control group. It was determined that UT-CCV has antidiabetic and antihypertensive effects. Therefore, our study encourages further clinical research on the alternative/complementary property of cornelian cherry vinegar in the treatment of various health manifestations including infections, cancer, diabetes, and hypertension. Novelty Impact Statement Bioactive components of organic cornelian cherry vinegar increased with ultrasound treatment. Organic cornelian cherry vinegar stimulates apoptosis in cancer cells. Vinegar samples prepared by the UT-CCV method show better antibacterial activity compared to CCV and P-CCV samples.Öğe ARID3A-mediated modulation of TP73 and TP73-AS1 in osteosarcoma cells(Elsevier Inc, 2020) Saadat, Khandakar A.S.M.; Bozgeyik, Esra; Arman, Kaifee; Bozgeyik, İbrahim; İkeda, M.A.Osteosarcoma is the most common primary malignancy arising from bone. Increasing mass of indications suggest that long non-coding RNAs (lncRNAs) play crucial roles in the development of progressions of human cancers including osteosarcoma. Although several lncRNAs have shown to be involved in the molecular pathogenesis of osteosarcoma, identification of novel lncRNAs involved in the osteosarcoma pathobiology remained muchly elusive. Besides, ARID3A is a member of ARID family of DNA binding proteins. ARID3A was also implicated in osteosarcoma pathogenesis. Accordingly, in the present study, we mechanistically investigated the effect of ARID3A on the expression of TP73 and TP73-AS1 in osteosarcoma cells and to determine the relationship between them. For the overexpression of ARID3A in U2-OS cells, pER_xpress_ARID3A expression vector and for the silencing of ARID3A, ARID3A-spesific siRNA was used. Expression levels of ARID3A, TP73 and TP73-AS1 genes were determined by qPCR method. As a result, expression levels of TP73-AS1 were well-correlated with the ARID3A expression levels whereas TP73 expression levels were not well-correlated with ARID3A. In conclusion, our results indicate that ARID3A might be involved in the regulation of TP73-AS1 in osteosarcoma. To our knowledge, this is the first study revealing the role of ARID3A in the regulation of TP73 and TP73-AS1 genes. © 2020 Elsevier Inc.Öğe Bioactive, Pro-Apoptotic-Angiotensin Converting Enzyme Inhibitor Effects and Properties of Ultrasound-Treated Traditional Poppy Vinegar Using the Response Surface Methodology Model(Amer Chemical Soc, 2024) Yikmis, Seydi; Bozgeyik, Esra; Demirok, Nazan Tokatli; Ilaslan, Kerem; Aadil, Rana MuhammadPoppy vinegar with functional properties is a fermented product. This study evaluated traditionally produced poppy vinegar. The study was conducted on poppy vinegar to determine the maximum increase in angiotensin converting enzyme (ACE) inhibitory activity %, total phenolic content (TPC), and radical scavenging activity (DPPH) of the vinegar at different combinations of ultrasound treatment duration (2-14 min) and amplitude (40-100%). The optimal parameters obtained using the response surface methodologies (RSM) were the duration of the ultrasound of 5.5 min and the amplitude of the ultrasound at 57%. When the DPPH values, ACE inhibition %, and TPC and DPPH values obtained with the RSM model were compared with the experimental values, the difference was 9.80, 3.0, and 4.6%, respectively, showing good agreement between actual and predicted values. The higher ultrasound intensities and longer treatment times had a significant effect on antioxidant activity. Poppy vinegar samples significantly induced the apoptosis of lung cancer cells, particularly those stored for 6 and 12 months. The amounts of protocatechuic acid, gallic acid, neohesperidin, hydroxybenzoic acid, resveratrol, rutin, trans-cinnamic acid, quercetin, and flavon in poppy vinegar were determined, which decreased significantly as storage time increased. TPC and TFC were determined to be 90.39 mg of GAE/100 mL and 29.86 mg of TEAC/mL, respectively, and there was no significant change in these bioactive compounds after 6 months of storage. The highest value of ACE inhibitory activity was found at the beginning of the storage period. The present study was the first study to examine the bioactive components, ACE inhibition activity, pro-apoptotic activities, and phenolic composition of traditionally produced ultrasound-treated poppy vinegar during storage. The control of production parameters and the design of ideal poppy vinegar fermentation processes could benefit from this research.Öğe Bioinformatic Analysis and in Vitro Validation of Let-7b and Let-7c in Breast Cancer(Elsevier Ltd, 2020) Bozgeyik, EsraMembers of the let-7 family of miRNAs are well-known with their tumor suppressor properties as they are expressed at low levels in several types of human malignancies. Among them, let-7b and let-7c have gained special attention due their broad significance. Although the role of let-7b and let-7c have been widely reported in various types of cancers, their functional importance and role in oncogenic signaling of breast cancer is poorly investigated. Therefore, in the present study, prognostic and diagnostic significance of let-7b and let-7c in breast cancer and the effects these miRNAs on genes involved in cancer progression were determined by using several bioinformatics analysis and validated in vitro mimic assays, respectively. Using data of TCGA, OncomiR and dbDEMC 2.0, overall expression analysis of let-7b and let-7c was performed. The effect of let-7b and let-7c on genes involved in cancer progression was investigated by mimic transfection assays. We found that both let-7b and let-7c were significantly altered in breast cancer and associated with the clinicopathological findings of patients. Additionally, both let-7b and let-7c significantly altered oncogenic signaling in breast cancer cells. Consequently, both miRNAs might have fundamental roles in breast cancer progression and can be considered as potential targets for breast cancer therapy and diagnosis. © 2019 Elsevier LtdÖğe Cross-regulation of non-coding RNAs and their correlations with target protein-coding genes in CRC pathobiology(Elsevier B.V., 2019) Bozgeyik, Esra; Bozgeyik, İbrahimIlluminating the correlations between non-coding RNAs and protein-coding genes are of great interest to understand more about the molecular mechanisms that drive malignant transformation and understanding such correlations will enable development of more specific and efficient targeted therapeutics. Accordingly, in this comprehensive meta-analysis study, we tried to determine correlations between long non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) molecules that are involved in the pathogenesis of colorectal cancer (CRC). For the present study, current colorectal cancer studies published until 20 August 2017 and associated with the lncRNA-miRNA-mRNA interactions was included. The current literature search was done online in Pubmed, Embase and Web of Science databases. These databases have been screened with three keywords; “lncRNA” “miRNA” and “colorectal cancer”. As a result, colorectal neoplasia differentially expressed (CRNDE) was determined to be consistently up-regulated in CRC tissues and inversely associated with miR-181a-5p. Also, CRNDE expression was significantly associated with lymph node metastasis (p = 0.032). Additionally, a significant association was determined between CRC and survival time in the OS analysis of FER1L4, TUSC7, UCC and lincRNA-ROR. More importantly, there was a negative correlation between lncRNA-miRNA expressions (p = 0.001). Particularly, CRNDE/miR-181a-5p, FER1L4/miR-106a-5p, TUSC7/miR-211, UCC/miR-143 and lincRNA-ROR/miR-145 was negatively correlated. In addition, there was a significant positive correlation between GAPLINC/CD44 and TUSC7/CDK6 in CRC tissues (p = 0.000). Overall analysis showed that lncRNAs and mRNAs, which are targets of the same miRNA, have positive interactions. In addition, miRNAs were shown to have negative correlations with target lncRNA/mRNA. © 2018 Elsevier B.V.Öğe Effects of Non-Thermal Treatment on Gilaburu Vinegar (Viburnum opulus L.): Polyphenols, Amino Acid, Antimicrobial, and Anticancer Properties(MDPI, 2022) Erdal, Berna; Yıkmış, Seydi; Demirok, Nazan Tokatlı; Bozgeyik, Esra; Levent, OkanSimple Summary In this study, traditionally produced vinegar made from gilaburu (C-GV) and thermally pasteurized gilaburu vinegar (P-GV), and (ultrasound-treated gilaburu vinegar (UT-GV) were evaluated. At the same time, ultrasound treatment enriched 11 phenolic compounds (gallic acid, protocatechuic acid, hydroxybenzoic acid, vanillic acid, p-coumaric acid, rutin, ferulic acid, o-coumaric acid, neohesperidin, quercetin, trans-cinnamic). Ultrasound showed different effects on free amino acids and volatile profiles. In general, ultrasound showed more positive results than thermal pasteurization. Six important minerals (Ca, Fe, K, Mg, Mn, and Zn) were detected in gilaburu vinegar, and ultrasound treatment increased the Fe content. Gilaburu vinegar, prepared by different methods, had potential antibacterial and anti-cancer activity. Gilaburu (Viburnum opulus L.) is an important fruit that has been studied in recent years due to its phytochemicals and health benefits. In this study, traditionally produced vinegar made from gilaburu fruit (C-GV) was evaluated. Vinegar with higher levels of bioactive components optimized by response surface methodology (RSM) was also produced using ultrasound (UT-GV). The maximum optimization result for the bioactive components was achieved at 14 min and 61.2 amplitude. The effectiveness of thermal pasteurization (P-GV) on gilaburu vinegar was evaluated. An increase was detected for every organic acid with ultrasound treatment. In the UT-GV and C-GV samples, arabinose was present, which is useful for stimulating the immune system. Gilaburu vinegar samples contained 29-31 volatile compounds. The smallest amount of volatile compounds was found in P-GV (1280.9 mu g/kg), and the largest amounts of volatile compounds were found in C-GV (1566.9 mu g/kg) and UT-GV (1244.10 mu g/kg). In the UT-GV sample, Fe was increased, but Ca, K, Mg, and Mn were decreased. A total of 15 polyphenols were detected in C-GV, P-GV, and UT-GV samples, and gallic acid was the most common. A total of 17 free amino acids were detected in gilaburu vinegar samples. Ultrasound provided enrichment in total phenolic compounds and total free amino acids. All three vinegar samples had good antimicrobial activity against pathogens. The efficacy of C-GV, P-GV, and UT-GV samples against colon and stomach cancer was determined, but there were no significant differences between them. As a result, ultrasound treatment is notable due to its antimicrobial and anticancer activity, especially for the enrichment of phenolic compounds and amino acids in gilaburu vinegar.Öğe Enhanced E2F1 activity increases invasive and proliferative activity of breast cancer cells through non-coding RNA CDKN2B-AS1(Elsevier B.V., 2020) Bozgeyik, Esra; Saadat, Khandakar A.S.M.; Arman, K.; Bozgeyik, İbrahim; İkeda, M.A.Long non-coding RNAs have recently appeared as fundamental regulators of gene transcription in several biological processes, but only a few have known functional influences in the malignant transformation of breast cancer. CDKN2B-AS1 gene, also termed ANRIL, encoding a long non-coding RNA is located in the CDKN2B-CDKN2A gene cluster, loss of which is the most frequent alternation in several types of human malignancies. CDKN2B-AS1 is involved in the suppression of tumor suppressor genes (INK4a, ARF, and INK4b) and has been recognized as a direct target of E2F1. However, the roles of E2F1–CDKN2B-AS1 interaction in breast cancer have remained muchly mysterious. In this particular study, we reveal that both CDKN2B and CDKN2B-AS1 genes were differentially expressed in breast cancer cells in contrast to breast epithelial cells. Ectopic expression of E2F1 activated CDKN2B-AS1 but not CDKN2B expression. Lastly, overexpression of E2F1 improved the colony formation and migratory capacities of breast cancer cells. These results suggest that enhanced E2F1 activity increased invasive and proliferative activity of breast cancer but not breast epithelial cells possibly through up-regulating CDKN2B-AS1 transcript. © 2020 Elsevier B.V.Öğe Evaluation of purple onion waste from the perspective of sustainability in gastronomy: Ultrasound-treated vinegar(Elsevier, 2022) Yıkmış, Seydi; Erdal, Berna; Bozgeyik, Esra; Levent, Okan; Yinanç, AbdullahSustainable gastronomy is an important concept that improves the health and nutritional quality of society by supporting the preparation, production, and consumption of foods with environmental awareness. Purple onion (Allium cepa) is a plant with rich bioactive properties, which is well known for its use in the field of gastronomy. In this study, for sustainable gastronomy, vinegar production was carried out using the traditional method and different methods using purple onion waste collected from restaurant businesses. At the same time, ultrasound technology was used to improve the nutritional properties of the vinegar, and some properties were compared with thermally pasteurized and untreated vinegar. The bioactive components of purple onion vinegar were enriched by ultrasound using response surface methodology (RSM). The maximum optimization result for the bioactive components was achieved at 58.2 amplitude and 6.4 min. The antihypertensive and antidiabetic effects of ultrasound-treated purple onion vinegar (UT-POV) were enhanced. The most commonly detected polyphenols, such as gallic acid, catechin, protocatechuic acid and hydroxybenzoic acid, increased with ultrasound treatment. K and Zn minerals were enriched in the UT-POV sample. UT-POV has less effect on volatile compounds than thermally pasteurized purple onion vinegar (P-POV). Our results show that UT-POV significantly impairs the proliferation of HGC-27 cells. Purple onion vinegar has strong anticancer and antimicrobial effects. Purple onion vinegar treated with ultrasound was evaluated positively for sustainable gastronomy.Öğe Influence of Ultrasonication and UV-C Processing on the Functional Characteristics and Anticarcinogenic Activity of Blackthorn Vinegar(Amer Chemical Soc, 2024) Gok, Sila Barut; Yikmis, Seydi; Levent, Okan; Bozgeyik, Esra; Ilaslan, Kerem; Aydin, Vahide GizemIn recent years, consumer trends have been changing toward fresh food products such as fruit juice, vinegar, etc. that are a good source of bioactive components, high nutritional characteristics, and beneficial microorganisms. Blackthorn (Prunus spinosa L.) vinegar (BV) is one of these nutritious foods. The study aims to examine the efficacy of ultraviolet-C (UV-C) light applied by a modified reactor and ultrasonication on bioactive compounds (total phenolic, total flavonoid, ascorbic acid content, and antioxidant activity) of traditionally produced BV. Furthermore, the volatile organic compound (VOC) profile, hydroxymethylfurfural (HMF) content, cytotoxicity properties, and color were assessed. UV-C light and ultrasonication processes enriched most bioactive components, but these methods did not significantly improve ascorbic acid (p > 0.05) compared to pasteurization. Twenty-seven volatile compounds were analyzed in order to determine the VOC profile. As a result, thermal and nonthermal methods were found to affect the profile significantly (p < 0.05). No significant differences were detected in total soluble solids (4.70-4.77), titratable acidity (3.81-3.87), and pH (3.39-3.41) values. The anticarcinogenic activities of UV-C-treated BVs were more significant than others. Nonthermal treatments were generally better than pasteurization in maintaining and enriching the quality of BV. In this study, UV-C light and ultrasonication technology can be used as an alternative to traditional thermal techniques to improve the quality of BV.Öğe Kanserin Ayırt Edici Özelliklerinde Kodlanmayan RNA'ların Rolü: Güncel Bir Bakış(2020) Bozgeyik, EsraKanser, genomda meydana gelen bir seri bozukluklar sonucu ortaya çıkan ciddi bir genetik hastalıktır. Yüksek verimli yeni nesil dizileme teknolojilerinin geliştirilmesi ve büyük ölçekli projelerin verilerinin yayınlanması farklı kanser türlerinde değişik ifade profili gösteren birçok kodlanmayan RNA (ncRNA) molekülünün tespit edilmesine olanak sağlamıştır. Uzun kodlanmayan RNA (lncRNA) ve mikroRNA (miRNA) gibi ncRNA transkriptlerinin kanserin oluşumunda ve ilerlemesinde kritik rollerinin olduğu ve kanser tanısında/tedavisinde kullanılabilir olduğu bildirilmiştir. Özellikle, miRNA’lar gen ifadesini post-transkripsiyonel seviyede kontrol eden ve kanserin önemli ayırt edici özellikleri olan metastaz, invazyon, hücre çoğalması, farklılaşması, anjiyogenez gibi önemli süreçlerde kritik rolleri olduğu bilinen küçük RNA molekülleridir. Benzer şekilde, lncRNA’lar da kanserin moleküler mekanizmasının aydınlatılmasında önemli yeri olan RNA transkriptleri olarak tanımlanmışlardır. Dolayısıyla, bu kapsamlı derlemede miRNA, lncRNA, T-UCR gibi protein kodlama kapasitesi olmayan ancak işlevsel olan ncRNA’lar ile kanserin ayırt edici özellikleri güncel bir bakış açısı ile ele alınmıştır.Öğe Küçük Hücreli Olmayan Akciğer Kanseri Hücrelerinde Let-7b-5p'nin Apoptotik Genler İle İlişkisinin Araştırılması(2019) Bozgeyik, EsraAmaç: Akciğer kanseri dünya genelinde kansere bağlı gerçekleşen ölümlerde kadınlarda ve erkeklerde ilk sıralarda yer almaktadır. Erken tanı yöntemlerinde ki gelişmeler ve yeni hedeflenen ajanların sayısının artmasına rağmen akciğer kanseri halen erken teşhis edilememekte ve etkin bir şekilde tedavi edilememektedir. Akciğer kanserinin tanısı için doğru ve güvenilir belirteçlere ihtiyaç duyulmaktadır. Ayrıca, akciğer kanserinde let-7b-5p’nin rolü ve terapötik potansiyelini ortaya koyan çalışmaların oldukça yetersiz olduğu gözükmektedir. Bu çalışmada A549 hücrelerinde let-7b-5p’nin ifade seviyesi miRNA mimik uygulaması ile arttırılarak apoptoz ile ilişkili genler ile ilişkisinin araştırılması amaçlanmıştır.Materyal ve Metot: Let-7b-5p’nin hedefi olabilecek apoptoz ile ilişkili genler onlineveri tabanlarından biyoinformatik araçlarla belirlenmiştir. Let-7b-5p’nin ifade seviyesinin A549 hücrelerinde arttırılması amacıyla, let-7b-5p mimiği hücrelereHiPerFect transfeksiyon ajanı ile transfekte edilmiştir. Daha sonra, elde edilen RNA’lardan let-7b-5p ve apoptoz ilişkili genlerin ifade seviyeleri qPCR yöntemi ile belirlenmiştir.Bulgular: Akciğer kanseri hücrelerinde let-7b-5p’nin ifade seviyesinin arttırılmasının ardından BCL2, RB1, XIAP, CASP9, TP53 ve PTEN genlerinin ifade seviyelerinin kontrol gruplarına kıyasla düştüğü bulunmuştur. Bunun aksine BAX geninin ifade seviyesinin arttığı ve CASP3 ve BCL2L1 genlerinin ifade seviyelerinde herhangi bir değişim olmadığı bulunmuştur. In silico analizler sonucunda TP53 geninin 3’ UTR bölgesinde iki farklı pozisyonda let-7b-5p bağlanma alanı olduğu gösterilmiştir.Sonuç: Sonuç olarak elde ettiğimiz bulgular let-7b-5p’nin apoptoz mekanizmasında yer alan genleri hedefleyebileceğini ve bu miRNA’nın akciğer kanserinin tanı ve/veya tedavisine yönelik önemli bir biyobelirteç olabileceğine işaret etmektedir.Öğe Long noncoding RNA ERICD interacts with ARID3A via E2F1 and regulates migration and proliferation of osteosarcoma cells(Blackwell Publishing Ltd, 2020) Arman, K.; Saadat, Khandakar A.S.M.; Iğcı, Y.Z.; Bozgeyik, Esra; İkeda, M.A.; Çakmak, Ecir Ali; Arslan, A.Long noncoding RNA (lncRNA) dysregulation is known to be taking part in majority of cancers, including osteosarcoma. In one of our previous studies, we showed that lncRNA MEG3 is being regulated by microRNA-664a (miR-664a) suppresses the migratory potential of osteosarcoma cells (U-2OS). We now report a novel lncRNA, namely, ERICD, which is linked to the transcription factor AT-rich interaction domain 3A (ARID3A) in U-2OS cells. We show that ARID3A binds to ERICD and indirectly interacts with each other via the E2F transcription factor 1 (E2F1). Furthermore, small interfering RNA (siRNA)-mediated knockdown of ERICD inhibited cell migration, formation of colonies, and proliferation in U-2OS cells. Overexpression of ARID3A inhibited cell migration, colony formation, and proliferation, whereas siRNA-mediated knockdown of ARID3A promoted cell migration, colony formation, and proliferation. Our findings indicate that ARID3A and lncRNA ERICD have plausible tumor suppressive and oncogenic functions, respectively, in osteosarcoma. Our data demonstrate the converse interaction between ARID3A and lncRNA ERICD that target DNA-binding proteins and dysregulation of their expression through E2F1 augments osteosarcoma progression. The cell rescue experiment also indicated E2F1 to be involved in the regulation of ARID3A and ERICD. © 2020 International Federation for Cell BiologyÖğe MicroRNA-17-5p targets expression of cancer-associated genes in breast cancer cells(Elsevier B.V., 2020) Bozgeyik, EsraAlthough there are several studies, biological function and therapeutic potential of miR-17-5p in breast cancer carcinogenesis remains muchly elusive. Specifically, its interaction with several cancer-associated genes remains unexplored in breast cancer. Here, we aimed to demonstrate the biological function and therapeutic potential of miR-17-5p in breast cancer through determination of the interactions between cancer-associated genes and miR-17-5p. MFC-7 breast cancer cells used in the study and cells were transfected with miR-17-5p miRNA mimics to ectopically overexpress miR-17-5p. MiR-17-5p expression levels and expression changes of cancer-associated genes were determined by using qPCR method. Expression levels of miR-17-5p were significantly enhanced following 72 h of mimic transfections as compared to scrambled control and blank control. Overexpression of miR-17-5p led to differential expression of several cancer-associated genes. Notably, BECN, CDKN2B and AIFM genes were significantly altered. Although not significant, expression levels of BAX, BCLXL, VIM, BCL2, MTOR, RB1, AKT1, XIAP, P53, and PTEN genes were found to be slightly elevated whereas expression levels of BCL-2, VIM and AKT1 were found to be decreased. Results of the present study indicate that miR-17-5p can act as both tumor suppressor and tumor promoter oncomiR in breast cancer. © 2019 Elsevier B.V.Öğe miR-320a promotes p53-dependent apoptosis of prostate cancer cells by negatively regulating TP73-AS1 in vitro(Academic Press Inc Elsevier Science, 2022) Bozgeyik, Esra; Arslan, Ahmet; Temiz, Ebru; Batar, Bahadır; Koyuncu, İsmail; Tozkır, HilmiTP73 antisense RNA 1 (TP73-AS1) is an oncogenic long non-coding RNA that is activated in several types of cancers. It has been shown that the activity of TP73-AS1 is controlled by several miRNAs, but post -transcriptional mechanisms that regulate TP73-AS1 activity in prostate cancer remain highly elusive. Accordingly, in the present study, we aimed to determine the miRNAs that are involved in the regulation of TP73-AS1 in prostate cancer and to show the effects of these molecules on the malignant proliferation of prostate cancer cells. Remarkably, colony formation and cell migration were suppressed while cell cycle arrest and apoptosis were induced in prostate cancer cells overexpressing miR-200a and miR-320a. miR-200a and miR-320a were found to be upregulated in TP73-AS1 suppressed prostate cancer cells. Also, TP73-AS1 was shown to be downregulated following miR-200a and miR-320a overexpression. However, overexpression of miR-320a had no significant effect on the expression of TP73. Further analysis revealed that miR-320a induces p53-dependent apoptosis. Consequently, our findings indicate that miR-320a induces p53-dependent apoptosis by negatively regulating TP73-AS1 long non-coding RNA.(c) 2022 Elsevier Inc. All rights reserved.Öğe MIRNA-mediated regulation of the PI3K/AKT signaling pathway in colorectal cancer: A study based on data mining(2019) Bozgeyik, Esra; Bozgeyik, İbrahimAim: In colorectal cancer (CRC), expression of genes involved in the PI3K/Akt signaling pathway varies significantly. Studies haveshown that microRNAs (miRNA) have important roles in the development of CRC. Accordingly, the aim of this study was to determinemiRNAs affecting the critical genes in the PI3K/Akt pathway by analysis of The Cancer Genome Atlas (TCGA) CRC data sets and toevaluate the clinical significance of these miRNAs.Material and Methods: Initially, CRC mRNA, miRNA expression levels and patient data were obtained from TCGA database. The studyincluded 220 CRC patients. MiRNAs that were negatively correlated with genes in the PI3K/Akt signaling pathway were selected, andtheir expression levels were compared with the clinical and demographic characteristics of CRC patients.Results: miR-18a, miR-19b, miR-17, miR-106b, miR-130b and miR-135b were found to be negatively correlated with genes that playkey roles in the PI3K/Akt pathway. Also, miR-18a, miR-19b, miR-17 and miR-135b were found to vary significantly according to theCRC subtype.Conclusion: Consequently, the PI3K/Akt signaling pathway was found to be deregulated in CRC and the majority of genes involved inthis signaling pathway were associated with miRNAs. Thus, PI3K/Akt miRNA axis might serve as a potentially distinctive diagnostic,prognostic and therapeutic avenue against CRC.Öğe Next generation sequencing analysis of BRCA1 and BRCA2 identifies novel variations in breast cancer(Elsevier Inc., 2020) Yıldız Tacar, Seher; Bozgeyik, Esra; Şeber, Erdoğan Selçuk; Yetişyiğit, Tarkan; Tozkır, Hilmi; Avcı, Okan; Arslan, AhmetMutations in two major breast cancer susceptibility genes, BRCA1 and BRCA2, have been identified to be the most important predisposing factors for the development of breast cancer. Thus, BRCA1/2 testing is a well-established method of choice for the assessment of developing breast cancer. Accordingly, here we aimed to report novel BRCA1/2 variations and distribution of previously known mutations and their association with the clinical course of breast cancer disease. A total of 287 breast cancer patients were enrolled from January 2017 through December 2019. Of these patients, 50 of them were identified to be positive for BRCA1/2. Next Generation Sequencing analysis was performed for the screening of exonic and intronic variations of BRCA1/BRCA2 genes. Notably, novel variations of 4448 G > A (Ser1843Asn) in BRCA1, and 982dupA (Thr328AspfsTer) and 7588C > T (Gln2530Ter) in BRCA2 gene were identified. The most common variations in BRCA1 gene were 5152 + 66G > A, 442-34C > T and 5266dupC. In BRCA2 gene, the most common variations were 9097dupA, 67 + 1G > A and 1114A > C. Novel variations of BRCA1 and BRCA2 genes were identified in breast cancer and might be useful predisposing factors in breast cancer diagnosis. © 2020 Elsevier Inc.Öğe Next-generation screening of a panel of genes associated with periodic fever syndromes in patients with Familial Mediterranean Fever and their clinical characteristics(Academic Press Inc., 2020) Bozgeyik, Esra; Mercan, Rıdvan; Arslan, A.; Tozkır, HilmiFamilial Mediterranean Fever (FMF) is a hereditary fever syndrome that primarily affects Mediterranean populations. For the study, total number of 182 patients with FMF disease were enrolled and screening of a panel of genes, called “fever panel” which comprises 17 genes, was performed. The most common mutations in MEFV gene were homozygous M694V missense mutation (4.3%) and R202Q missense mutation (4.9%). The most common heterozygous mutations were R202Q (26.5%), M694V (25.9%) and E148Q (11.9%). Compound heterozygous and homozygous mutations were also detected. Also, different types of mutations were identified in NOD2, CARD14, NLRP12, NLRP3, NLRP7, IL1RN, LPIN2, TNFRSF1A, MVK and PSTPIP1 genes. Two novel missense variations in the MEFV gene, Gln34Pro and Ile247Val, which have not been previously reported in the databases, were identified. Also, Thr91Ile missense variation in the NOD2 gene, Gly461Cys missense variation in NLRP3 and Tyr732Stop nonsense variation in LPIN2 were firstly identified. The results of the current study suggest that in addition to the MEFV gene which has an important roles in FMF, molecular screening of other genes related to other autoinflammatory diseases might provide support in suspected cases and provide detailed information about the course of the disease. © 2020 Elsevier Inc.Öğe Novel thiosemicarbazone derivative 17B interferes with the cell cycle progression and induce apoptosis through modulating downstream signaling pathways(Elsevier, 2020) Bozgeyik, Esra; Taşdemir Kahraman, Demet; Arman, Kaifee; Bozgeyik, İbrahim; Karaküçük İyidoğan, Ayşegül; Çakmak, Ecir AliThiosemicarbazones (TSCs) are interesting group of chemical compounds that received significant levels of attention due their wide range of pharmacological effects including antibacterial, antiviral, and especially anti-tumor activities. Several thiosemicarbazone derivatives have been extensively reported recently with their anti-tumor properties but designing and developing novel thiosemicarbazone derivatives with more potent chemotherapeutic activities is of great interest for cancer future cancer therapy. Thus, here we aimed to demonstrate as yet undetermined anti-cancer properties of novel thiosemicarbazone derivative 17B. Viability of cells was determined using MTT assay and LDH activities were analyzed using lactate dehydrogenase activity assay. Apoptosis were assayed using Annexin V-FITC and PI double staining method and cell cycle analysis was achieved by using PI staining with fluorescence-activated cell sorting and migration capacities of cells were determined by wound healing assay. As a result, 17B limited cell viability and showed cytotoxic effects in a dose-dependent manner in A549, MCF7 and U2OS cells. In addition, it inhibited progression through cell cycle by interfering with the Gl/S transition and triggered apoptosis by modulating expression levels of pro-apoptotic and anti-apoptotic mediators in MCF7 and U2OS cells. Also, 17B significantly impaired the migration of cancer cells and delayed wound healing in all cells. Consequently, findings of the present study have strongly indicated that 17B might be a novel anti-cancer agent for the treatment of breast cancer and osteosarcoma but not for lung cancer. Our results have provided mechanistic insights into anti-cancer properties of a novel thiosemicarbazone derivative 17B.Öğe Novel zinc oxide nanoparticles of Teucrium polium suppress the malignant progression of gastric cancer cells through modulating apoptotic signaling pathways and epithelial to mesenchymal transition(Elsevier, 2023) Bozgeyik, İbrahim; Ege, Miray; Temiz, Ebru; Erdal, Berna; Koyuncu, İsmail; Temiz, Cengiz; Bozgeyik, EsraManagement of gastric cancer is still challenging due to resistance to current chemotherapeutics and recurrent disease. Moreover, green-synthesized zinc oxide nanoparticles (ZnO-NPs) using natural resources are one of the most promising therapeutic agents for anticancer therapy. Here we report the facile green synthesis and char-acterization of ZnO-NPs from Teucrium polium (TP-ZnO-NP) herb extract and the anticancer activities of these nanoparticles on gastric cancer cells. Facile green synthesis of TP-ZnO-NP was achieved using zinc acetate dihydrate. For the characterization of TP-ZnO-NP, UV-vis spectroscopy, FTIR, SEM, XRD and EDX analyses were performed. Antiproliferative and anticancer activities of TP-ZnO-NP were explored using the HGC-27 gastric cancer cell line model. MTT cell viability and colony formation assays were used for the analysis of cell pro-liferation and migration. Wound healing assay was used to analyze the migration capacities of cells. Annexin V/ PI double staining, DNA ladder assay, and Acridine orange/Ethidium bromide staining were performed to analyze the induction of apoptosis. qPCR was used to determine gene expression levels of apoptotic and epithelial to mesenchymal transition marker genes. The aqueous extract of TP served as both a reducing and capping agent for the successful biosynthesis of zinc oxide nanoparticles. Remarkably, synthesized TP-ZnO-NPs were found to have significant antiproliferative and anticancer activities on HGC-27 gastric cancer cells. Collectively, current data suggest that TP-ZnO-NP is a novel and promising anticancer agent for future therapeutic interventions in gastric cancer.Öğe Organic cherry laurel (Prunus laurocerasus) vinegar enriched with bioactive compounds with ultrasound technology using artificial neural network (ANN) and response surface methodology (RSM): Antidiabetic, antihypertensive, cytotoxic activities, volatile profile and optical microstructure(John Wiley and Sons Inc, 2021) Yıkmış, Seydi; Bozgeyik, Esra; Levent, Okan; Aksu, HarunThis research aimed to enrich the bioactive components of organic cherry laurel vinegar with ultrasound and to examine the correlation between artificial neural network (ANN) and response surface methodology (RSM), and compare some of the quality parameters of bioactive-enriched organic cherry laurel vinegar (UT-CLV), thermally pasteurized cherry laurel vinegar (P-CLV), and unprocessed organic cherry laurel vinegar (CLV). UT-CLV preserved and improved its volatile aroma profile more than the P-CLV sample. With ultrasound treatments, it provided positive effects on the antidiabetic and antihypertensive activities of organic cherry laurel vinegar. Also, organic cherry laurel vinegar was found to significantly inhibit the viability of prostate cancer cells, but not breast and lung cancer cells. As a result, it has been found that ultrasound technology enriches the bioactive components of organic cherry laurel vinegar according to thermal pasteurization and is successful in increasing its antidiabetic and antihypertensive effects. Novelty impact statement: Bioactive components of organic cherry laurel vinegar were enriched with ultrasound treatment. Its antidiabetic, antihypertensive, and anticarcinogenic effects were found to be successful with ultrasound treatment. ANN and RSM had high prediction accuracy in different bioactive components. © 2021 Wiley Periodicals LLC.
