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Öğe Anti-Inflammatory Effect of Crude Momordica charantia L. Extract on 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis Model in Rat and the Bioaccessibility of its Carotenoid Content(Mary Ann Liebert, Inc, 2020) Unal, Nalan Gulsen; Kozak, Ayseguel; Karakaya, Sibel; Oruc, Nevin; Barutcuoglu, Burcu; Aktan, Cagdas; Sezak, MuratMomordica charantia L., known as bitter melon (BM), is a plant that belongs to the family Cucurbitaceae. Aims of this study are to investigate the anti-inflammatory effect of crude BM extract on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model in rat. It was also aimed to determine the content and bioaccessibility of carotenoids of BM. BM was purchased from local markets in Izmir, Turkey. Fruits of BM were lyophilized, powdered, and used in the experiment. Carotenoids were determined by high-performance liquid chromatography. To determine the bioaccessibility of beta-carotene, in vitro digestion was performed. Wistar albino rats were divided into four groups: group A (BM+TNBS), group B (BM), group C (TNBS), and group D (control). BM solution was given 300 mg/(kg center dot day) for 6 weeks orally. Colitis was induced by 0.25 mL of a solution containing 100 mg/kg 5% (w/v) TNBS in 50% ethanol (w/v) intrarectally after 6 weeks. After sacrification, macroscopic and microscopic evaluations were performed. Myeloperoxidase, cytokines levels (interleukin-17 [IL-17], TNF-alpha, and interleukin-10 [IL-10]) were measured in serum and colonic samples by ELISA test. Institutional Animal Ethics Committee approval was obtained. Total carotenoid content of BM was determined 11.7 mg/g dry weight as beta-carotene equivalents. Bioaccessibility of total carotenoids was determined as 2.1% with in vitro digestion. Pretreatment with crude BM extract significantly reduced weight loss, macroscopic, and microscopic colitis damages in colonic samples (P = .000), (P = .015), and (P = .026), respectively. Serum anti-inflammatory cytokine IL-10 increased significantly in both treatment groups (P = .000). BM is a rich source of carotenoids, but the bioaccessibility of its carotenoids is low. This study displays that BM has protective anti-inflammatory effects on TNBS-induced colitis.Öğe CHRM3-Associated miRNAs May Play a Role in Bile Acid-Induced Proliferation of H508 Colon Cancer Cells(Aves, 2023) Aktan, Cagdas; Tekin, Fatih; Oruc, Nevin; Ozutemiz, OmerBackground: It was well defined that proliferative effects of bile acids on colon epithelium are through interaction with muscarinic-3 receptors. Recently, microRNA emerged as an important regulator of gene expression and has been implicated in pathogenesis of many malignancies. However, the interaction of CHRM3 and microRNAs and their potential effects on colon carcinogenesis remains to be elucidated. Methods: In the current study, analysis of cell proliferation for 6 days after treatment with sodium taurolithocholate was analyzed by using WST-1 method. microRNAs which possibly target CHRM3 were identified by in silico analyses. Expression profiling of these microRNAs, expression changes of CHRM3 gene at mRNA level for H508 and SNU-C4 colon cancer cells were analyzed by quantitative polymerase chain reaction; the protein level of CHRM3 was analyzed using Western blot; apoptotic experiments were analyzed using the Annexin V assay. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the miRPath v3.0. Results: It was found that the expression level of CHRM3 gene was 6.133 +/- 0.698-fold in H508 cells compared with SNU-C4 cells (P =.004). Treatment of H508 cells with sodium taurolithocholate caused 1.34 +/- 0.4156-fold change in the expression level of CHRM3 gene (P =.0448). No apoptotic changes were observed in both colon cancer cells after treatment with sodium taurolithocholate. Different expression changes were detected of hsa-miR-129-5p, hsa-miR-30c-5p, hsa-miR-224-5p, hsa-miR-30b-5p, hsa-miR-522-3p, and hsa-miR-1246. Finally, hsa-miR-1246 and hsa-miR-522-3p could play a critical role in tumor development via bile acid-related genes in colon cancer. Conclusion: These findings reflected that CHRM3-dependent oncogenetic pathways might be in charge of colon cancer. We suggest that the microRNA expression profile of each individual colon cancer tissue is a unique digital signature.Öğe Combination of dasatinib and okadaic acid induces apoptosis and cell cycle arrest by targeting protein phosphatase PP2A in chronic myeloid leukemia cells(Humana Press Inc, 2022) Ozel, Buket; Kipcak, Sezgi; Avci, Cigir Biray; Gunduz, Cumhur; Saydam, Guray; Aktan, Cagdas; Gunel, Nur SelviChronic myeloid leukemia (CML) is a cancer type of the white blood cells and because of BCR-ABL translocation it results in increased tyrosine kinase activity. For this purpose, dasatinib is the second-generation tyrosine kinase inhibitor that is used for inhibition of BCR-ABL. Effectively and safetly, dasatinib has been used for imatinib-intolerant/resistant CML patients. Protein phosphatase 2A (PP2A) is the major serine/threonine phosphatase ensuring cellular homeostasis in cells and is associated with many cancer types including leukemias. In this study, we aimed to investigate the effects of dasatinib and okadaic acid (OA), either alone or in combination, on apoptosis and cell cycle arrest and dasatinib effect on enzyme activity and protein-level changes of PP2A in K562 cell line. The cytotoxic effects of dasatinib were evaluated by WST-1 analysis. Apoptosis was determined by Annexin V and Apo-Direct assays by flow cytometry. Cell cycle arrest analysis was performed for the investigation of the cytostatic effect. We also used OA as a PP2A inhibitor to assess apoptosis and cell cycle arrest changes in case of reducing the level of PP2A. PP2A enyzme activity and protein levels of PP2A were examined by serine/threonine phosphatase assay and Western blot analysis, respectively. Apoptosis was increased with dasatinib and OA combination. Cell cycle arrest was determined especially after OA treatment. The enzyme activity was decreased depending on time after dasatinib application. PP2A regulatory and catalytic subunit protein levels were decreased compared to control. Targeting the PP2A by dasatinib and OA has potential for CML treatment.Öğe Decreased circulating microRNA-21 and microRNA-143 are associated to pulmonary hypertension(Tubitak Scientific & Technological Research Council Turkey, 2023) Duzgun, Zekeriya; Kayikcioglu, Meral; Aktan, Cagdas; Bara, Busra; Eroglu, Zuhal; Yagmur, Burcu; Cetintas, Vildan BozokBackground/aim: Pulmonary arterial hypertension (PAH) is characterized by maladaptation of pulmonary vasculature which is leading to right ventricular hypertrophy and heart failure. miRNAs play a crucial role in the regulation of many diseases such as viral infection, cancer, cardiovascular diseases, and pulmonary hypertension (PH). In this study, we aimed to investigate the expression pattern of eight human plasma miRNAs (hsa-miR-21-3p, hsa-miR-143-3p, hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204-3p, hsa-miR-206, hsa-miR-210-3p) in mild-to-severe PH patients and healthy controls.Materials and methods: miRNAs were extracted from the peripheral plasma of the PH patients (n: 44) and healthy individuals (n: 30) by using the miRNA Isolation Kit. cDNA was synthesized using All in-One First strand cDNA Synthesis Kit. Expression of the human plasma hsa-miR-21-3p, hsa-miR-143-3p, hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204-3p, hsa-miR-206, hsa-miR-210-3p, and miRNAs were analyzed by qRT-PCR.Results: According to our results, in PH patients hsa-miR-21-3p and hsa-miR-143-3p expression levels were decreased by 4.7 and 2.3 times, respectively. No significant changes were detected in hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204-3p, hsa-miR-206, and hsa-miR-210-3p expression levels between PH and control groups. In addition, considering the severity of the disease, it was observed that the decrease in miR-138, miR-143, miR-145, miR-190, mir-204, mir-206 and miR-208 expressions was significant in patients with severe PH.Conclusion: In the early diagnosis of PAH, hsa-miR-21-3p and especially hsa-miR-143-3p in peripheral plasma can be considered as potential biomarkers.Öğe Expression of salivary LINC01206, LINC01209, LINC01994, and ABCC5-AS1 may serve as diagnostic tools in laryngeal cancer(Elsevier, 2022) Aktan, Cagdas; Kucukaslan, Ali Sahin; Cengiz, A. Bugra; Demirci, Mehmet; Sunter, Volkan; Baygul, Arzu; Dalmizrak, AysegulPurpose of the study: lncRNAs appear to act as an important epigenetic regulator of the immune response to bacterial infection in mammals. However, a lncRNA that only exhibits pathogenic or beneficial potential during infection has not yet been described. Moreover, it is still not fully known whether there are specific lncRNAs whose expression changes in response to a particular pathogen or whether lncRNAs are mainly involved in basic cellular immune responses to different stress stimuli. This study aims to assess association between salivary lncRNAs and salivary bacterial pathogens in laryngeal cancer patients. Methods: LINC01206, LINC01209, LINC01994, and ABCC5-AS1 were analyzed among 13 candidate lncRNAs in the saliva samples of 35 patients with laryngeal carcinoma and 25 healthy control. Both their expressions and the quantitative amount of oral bacteria members (Rothia mucilaginosa, Streptococcus spp., Prevotella oris, Veillonella dispar, Neisseria subflava, and Peptostreptococcus stomatis) were analyzed using qPCR. To determine whether these lncRNAs and bacterial pathogens are useful as diagnostic biomarkers, their association with clinicopathological and demographic characteristics was analyzed. Results: When the study group compared with the control group, expression of LINC01206, LINC01209, LINC01994, and ABCC5-AS1 were 2.84-fold, 2.33-fold, 4.46-fold, and 2.27-fold lower, respectively (p < 0.05). In terms of the amount of bacteria DNA in saliva, no significant difference was found between the laryngeal cancer and the control groups (p > 0.05). Conclusion: These results may provide novel insights into the molecular mechanism underlying laryngeal cancer and lncRNA/microbiome applications may constitute a new and alternative method to prevent development of laryngeal cancer in the future.Öğe Functional roles of miR-625-5p and miR-874-3p in the progression of castration resistant prostate cancer(Pergamon-Elsevier Science Ltd, 2022) Aktan, Cagdas; Cal, Cag; Kaymaz, Burcin; Gunel, Nur Selvi; Kipcak, Sezgi; Ozel, Buket; Gunduz, CumhurAims: Androgen receptor (AR) signaling is important in normal prostate and prostate tumor tissues. Thus, the new therapeutic strategies targeting ARs may also be important for treatment of prostate cancer (PC) and its biology. The studies have shown that miRNAs to be dysregulated in PC progression. Therefore, in the present study, differentially expressed miRNAs that predictively target the ARs were identified and investigated by in silico analysis. Main methods: Cellular proliferation, qPCR, western blot and apoptosis assays were performed to investigate the molecular mechanism of the selected miRNAs in the PC cells. Key findings: In our miRNA qPCR study, several miRNAs were found to be differentially regulated in castration resistant prostate cancer (CRPC) cells (LNCaP-Abl and LNCaP-104R2) compared with androgen dependent (AD) cells (LNCaP). The expression levels of miR-625-5p and miR-874-3p were significantly increased in LNCaP-Abl (2.62-fold, p = 0.0002; 4.00-fold, p = 0.00002, respectively) and LNCaP-104R2 (2.44-fold, p = 0.0455; 3.77 fold, p = 0.0383, respectively) compared with AD cells. The expression levels of AR and prostate specific antigen were increased in PC cells compared with AD cells. Furthermore, transfection of PC cells with anti-miRs suppressed their proliferation and AR protein levels (p < 0.05). Significance: Several differentially regulated miRNAs were identified in CRPC cells, including miR-625-5p and miR-874-3p that are potentially involved in PC progression. These results may provide novel insights into the molecular mechanism underlying CRPC cells and miRNA applications may constitute a new and alternative method to prevent development of CRPC cells in the future.Öğe Oral microbial dysbiosis in patients with oral cavity cancers(Springer Heidelberg, 2024) Unlu, Ozge; Demirci, Mehmet; Paksoy, Tugce; Eden, Arzu Baygul; Tansuker, Hasan Deniz; Dalmizrak, Aysegul; Aktan, CagdasObjectives The pathogenesis of oral cavity cancers is complex. We tested the hypothesis that oral microbiota dysbiosis is associated with oral cavity cancer. Materials and methods Patients with primary oral cavity cancer who met the inclusion and exclusion criteria were included in the study. Matching healthy individuals were recruited as controls. Data on socio-demographic and behavioral factors, self-reported periodontal measures and habits, and current dental status were collected using a structured questionnaire and periodontal chartings. In addition to self-reported oral health measures, each participant received a standard and detailed clinical examination. DNA was extracted from saliva samples from patients and healthy controls. Next-generation sequencing was performed by targeting V3-V4 gene regions of the 16 S rRNA with subsequent bioinformatic analyses. Results Patients with oral cavity cancers had a lower quality of oral health than healthy controls. Proteobacteria, Aggregatibacter, Haemophilus, and Neisseria decreased, while Firmicutes, Bacteroidetes, Actinobacteria, Lactobacillus, Gemella, and Fusobacteria increased in oral cancer patients. At the species level, C. durum, L. umeaens, N. subflava, A. massiliensis, and V. dispar were significantly lower, while G. haemolysans was significantly increased (p < 0.05). Major periodontopathogens associated with periodontal disease (P. gingivalis and F.nucleatum) increased 6.5- and 2.8-fold, respectively. Conclusion These data suggested that patients with oral cancer had worse oral health conditions and a distinct oral microbiome composition that is affected by personal daily habits and may be associated with the pathogenicity of the disease and interspecies interactions. Clinical relevance This paper demonstrates the link between oral bacteria and oral cancers, identifying mechanistic interactions between species of oral microbiome.Öğe Ponatinib and STAT5 Inhibitor Pimozide Combined Synergistic Treatment Applications Potentially Overcome Drug Resistance via Regulating the Cytokine Expressional Network in Chronic Myeloid Leukemia Cells(Mary Ann Liebert, Inc, 2024) Tezcanli Kaymaz, Burcin; Gumus, Nurcan; Celik, Besne; Alcitepe, Ilayda; Biray Avci, Cigir; Aktan, CagdasChronic myeloid leukemia (CML) is a clonal myeloproliferative hematological disease characterized by the chimeric breakpoint-cluster region/Abelson kinase1 (BCRÖğe The Role of Endoplasmic Reticulum Stress in Gastroesophageal Reflux Disease Symptoms and Treatment(Aves, 2023) Kasap, Elmas; Buran, Tahir; Avcu, Aysun Toraman; Hasdemir, Pinar Solmaz; Balcan, Erdal; Aktan, Cagdas; Korkmaz, MehmetBackground: Gastroesophageal reflux disease is a common condition worldwide. There is no curative treatment for gastroesophageal reflux disease. Endoplasmic reticulum stress leads to the activation of the unfolded protein response and has an important role in inflammation. The aim is to determine the role of endoplasmic reticulum stress in the follow-up of individuals with gastroesophageal reflux disease and the temporal changes of endoplasmic reticulum stress markers with treatment. Methods: Twenty-four subjects in total were recruited prospectively, of whom 15 had nonerosive reflux disease. Two biopsies from 2 cm above the esophagogastric junction, 2 biopsies from gastric antrum mucosa, and 2 biopsies from gastric corpus mucosa were taken. Simultaneously, 2 tubes of venous blood samples were drawn from each individual (1 tube for studying the genetic markers and 1 tube for analyzing the CYP2C19 polymorphism). Results: The mean age was 42.3 +/- 17.6 for women and 34.66 +/- 11.2 for men. Pantoprazole, esomeprazole, rabeprazole, and lansoprazole preparations were used for treatment. There was no significant difference between tissue and blood samples for panel genes ATF-6, XBP-1, DDIT-3, DNAJC-10, and EIF-2-AK before treatment. There was a significant decrease in the level of ATF-6, XBP-1, DNAJC-9, EIF2-AK, and NF-2L-2 genes in blood after treatment. In the comparison of proton pump inhibitors, significant decreases in the expression of the ATF-6, XBP-1, and DNAJC-9 mRNAs were detected in blood from individuals after treatment. Conclusion: Endoplasmic reticulum stress can be for evaluating the clinical improvement and the effectiveness of treatment in gastroesophageal reflux disease.