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Article ; Online: Preparation and characterization of lipid nanoparticle/pDNA complexes for STAT3 downregulation and overcoming chemotherapy resistance in lung cancer cells.

Kotmakçı, Mustafa / Çetintaş, Vildan Bozok / Kantarcı, A Gülten

2017 Volume 525, Issue 1, Page(s) 101–111

Abstract: Developments in the field of molecular oncology have revealed that resistance to chemotherapeutics is acqured through several mechanisms including overexpression of common oncogenic proteins. Signal Transducer and Activator of Transcription 3 (STAT3) is ... ...

Abstract	Developments in the field of molecular oncology have revealed that resistance to chemotherapeutics is acqured through several mechanisms including overexpression of common oncogenic proteins. Signal Transducer and Activator of Transcription 3 (STAT3) is one of these oncogenes that is overexpressed in many cancer types. RNA interference (RNAi) is proven powerful tool for downregulating STAT3, allowing re-sensitization of resistant cancer cells. However, delivery of RNA interference-mediating molecules for STAT3 downregulation in lung cancer cells is limited to a small number of studies most of which employ commercially available transfection kits. The aim of this study was to develop and evaluate cationic solid lipid nanoparticles for delivery of RNAi-mediating plasmid DNA in order to down regulate STAT3 in cisplatin resistant lung cancer cells. We focused on obtaining cSLN:plasmid DNA complexes with size below or equal to 100nm, and a positive zeta potential. Two successful candidate cSLN:plasmid DNA complexes (K2 and K3) were selected for in vitro tests and cell culture studies. These formulations have particle sizes of 98 and 93nm, and zeta potential values of 10.5 and 8.9mV, respectively. Plasmid DNA in these complexes was protected against DNaseI and serum-mediated degradation. Substantial part of DNA retained its supercoiled and circular conformation. TEM images showed nearly spherical complex structure. Both formulations reduced STAT3 expression by approx. 5-fold in cisplatin resistant Calu1 cell line and increased the sensitivity of cells to cisplatin.
Language	English
Publishing date	2017-06-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2017.04.034
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Zs.A 1409: Show issues

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Article ; Online: Decreased circulating microRNA-21 and microRNA-143 are associated to pulmonary hypertension.

Düzgün, Zekeriya / Kayıkçıoğlu, Latife Meral / Aktan, Çağdaş / Bara, Buşra / Eroğlu, Fatma Zuhal / Yağmur, Burcu / Çetintaş, Vildan Bozok / Bayındır, Melike / Nalbantgil, Sanem / Vardarli, Aslı Tetik

Turkish journal of medical sciences

2023 Volume 53, Issue 1, Page(s) 130–141

Abstract: Background: 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 ...

Abstract	Background: 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, hsamiR-206, hsa-miR-210-3p) in mild-to-severe PH patients and healthy controls. 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-miR210-3p, 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, hsamiR-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. Discussion: : 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.
MeSH term(s)	Humans ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Hypertension, Pulmonary/genetics ; RNA, Circular/genetics ; Biomarkers ; Gene Expression Regulation
Chemical Substances	MIRN143 microRNA, human ; MIRN21 microRNA, human ; RNA, Circular ; Biomarkers
Language	English
Publishing date	2023-02-22
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	1183461-4
ISSN	1303-6165 ; 1300-0144
ISSN (online)	1303-6165
ISSN	1300-0144
DOI	10.55730/1300-0144.5566
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Zs.A 3242: Show issues

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Article ; Online: Molecular dynamic simulation and functional analysis of pathogenic PTEN mutations in glioblastoma.

Cetintas, Vildan Bozok / Duzgun, Zekeriya / Akalin, Taner / Ozgiray, Erkin / Dogan, Eda / Yildirim, Zafer / Akinturk, Nevhis / Biceroglu, Huseyin / Ertan, Yesim / Kosova, Buket

Journal of biomolecular structure & dynamics

2023 Volume 41, Issue 21, Page(s) 11471–11483

Abstract: PTEN, a dual-phosphatase and scaffold protein, is one of the most commonly mutated tumour suppressor gene across various cancer types in human. The aim of this study therefore was to investigate the stability, structural and functional effects, and ... ...

Abstract	PTEN, a dual-phosphatase and scaffold protein, is one of the most commonly mutated tumour suppressor gene across various cancer types in human. The aim of this study therefore was to investigate the stability, structural and functional effects, and pathogenicity of 12 missense
MeSH term(s)	Humans ; Glioblastoma/genetics ; Molecular Dynamics Simulation ; Mutation ; Mutation, Missense ; PTEN Phosphohydrolase/genetics
Chemical Substances	PTEN protein, human (EC 3.1.3.67) ; PTEN Phosphohydrolase (EC 3.1.3.67)
Language	English
Publishing date	2023-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	49157-3
ISSN	1538-0254 ; 0739-1102
ISSN (online)	1538-0254
ISSN	0739-1102
DOI	10.1080/07391102.2022.2162582
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Zs.A 2093: Show issues

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Article ; Online: Cytotoxicity of Dental Implants: The Effects of Ultrastructural Elements.

Cal, Ebru / Cetintas, Vildan Bozok / Boyacioglu, Hayal / Güneri, Pelin

The International journal of oral & maxillofacial implants

2017 Volume 32, Issue 6, Page(s) 1281–1287

Abstract: Purpose: In this in vitro study, the purpose was to assess the cytotoxicity profiles of seven commercial dental implant materials by using cell culture methods on an osteoblastic cell line.: Materials and methods: The microstructure of seven ... ...

Abstract	Purpose: In this in vitro study, the purpose was to assess the cytotoxicity profiles of seven commercial dental implant materials by using cell culture methods on an osteoblastic cell line. Materials and methods: The microstructure of seven commercial dental implants (each given a letter code) was investigated via scanning electron microscopy and energy-dispersive x-ray analysis. Medium extracts were collected on the first and fifth days for each group and tested using MC3T3-E1 cell line. Cytotoxicity was evaluated with Xcelligance System and XTT reagent, and apoptosis was determined by Annexin-V staining. One-way analysis of variance (ANOVA) and Tukey's multiple range tests were used for statistical analyses. In all tests, P was set as .05. Results: ANOVA results disclosed that Ti (P = .001), Na (P = .001), Ca (P = .019), Al (P = .024), and P (P = .020) amounts were significantly different between test materials. Cytotoxicity and apoptosis analyses revealed that implant materials (C) and (E) were the materials with the lowest cell vitality and the highest apoptosis rates among the test materials. Phosphorus was the only element that presented the highest amount in C and E (14.23% and 12.29%, respectively) compared with the other implant materials tested. (F) and (G) had favorable results for all experiments. Conclusion: The results suggest that pure dental implant materials with a lower number of additional elements may possess fewer cytotoxic effects than the other implant materials tested in this study.
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	632880-5
ISSN	1942-4434 ; 0882-2786
ISSN (online)	1942-4434
ISSN	0882-2786
DOI	10.11607/jomi.5962
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Zs.A 2179: Show issues

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Article ; Online: Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia (T-ALL) cells.

Tetik Vardarlı, Aslı / Düzgün, Zekeriya / Erdem, Ceren / Kaymaz, Burçin Tezcanli / Eroglu, Zuhal / Çetintas, Vildan Bozok

Bosnian journal of basic medical sciences

2018 Volume 18, Issue 2, Page(s) 141–149

Abstract: Matrine, a natural product extracted from the root of Sophora flavescens, is a promising alternative drug in different types of cancer. Here, we aimed to investigate the therapeutic effects and underlying molecular mechanisms of matrine on human acute ... ...

Abstract	Matrine, a natural product extracted from the root of Sophora flavescens, is a promising alternative drug in different types of cancer. Here, we aimed to investigate the therapeutic effects and underlying molecular mechanisms of matrine on human acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM. Cell viability and IC50 values were determined by WST-1 cell cytotoxicity assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Expression patterns of 44 selected miRNAs and 44 RNAs were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using the Applied Biosystems 7500 Fast Real-Time PCR System. Matrine inhibited cell viability and induced apoptosis of CCRF-CEM cells in a dose-dependent manner. Cell cycle analysis demonstrated that matrine-treated CCRF-CEM cells significantly accumulated in the G0/G1 phase compared with the untreated control cells. hsa-miR-376b-3p (-37.09 fold, p = 0.008) and hsa-miR-106b-3p (-16.67 fold, p = 0.028) expressions were decreased, whereas IL6 (95.47 fold, p = 0.000011) and CDKN1A (140.03 fold, p = 0.000159) expressions were increased after matrine treatment. Our results suggest that the downregulation of hsa-miR-106b-3p leads to the upregulation of target p21 gene, CDKN1A, and plays a critical role in the cell cycle progression by arresting matrine-treated cells in the G0/G1 phase.
MeSH term(s)	Alkaloids/pharmacology ; Antineoplastic Agents/pharmacology ; Apoptosis ; Autophagy ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Fragmentation ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; G1 Phase ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Humans ; Inhibitory Concentration 50 ; Interleukin-6/metabolism ; MicroRNAs/metabolism ; Plant Extracts/pharmacology ; Plant Roots/chemistry ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Quinolizines/pharmacology ; Resting Phase, Cell Cycle ; Sophora/chemistry
Chemical Substances	Alkaloids ; Antineoplastic Agents ; CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p21 ; IL6 protein, human ; Interleukin-6 ; MIRN106 microRNA, human ; MIRN376C microRNA, human ; MicroRNAs ; Plant Extracts ; Quinolizines ; matrine (N390W430AC)
Language	English
Publishing date	2018-05-20
Publishing country	Bosnia and Herzegovina
Document type	Journal Article
ZDB-ID	2240029-1
ISSN	1840-4812 ; 1512-8601
ISSN (online)	1840-4812
ISSN	1512-8601
DOI	10.17305/bjbms.2017.2457
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Zs.A 6314: Show issues

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Article ; Online: MicroRNA-520a-5p displays a therapeutic effect upon chronic myelogenous leukemia cells by targeting STAT3 and enhances the anticarcinogenic role of capsaicin.

Kaymaz, Burçin Tezcanlı / Cetintaş, Vildan Bozok / Aktan, Cağdaş / Kosova, Buket

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

2014 Volume 35, Issue 9, Page(s) 8733–8742

Abstract: Aberrant expression profiles of microRNAs (miRNAs) have been previously demonstrated for having essential roles in a wide range of cancer types including leukemia. Antiproliferative or proapoptotic effects of capsaicin have been reported in several ... ...

Abstract	Aberrant expression profiles of microRNAs (miRNAs) have been previously demonstrated for having essential roles in a wide range of cancer types including leukemia. Antiproliferative or proapoptotic effects of capsaicin have been reported in several cancers. We aimed to study miRNAs involved in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in chronic myeloid leukemia cell model and the effects of the capsaicin treatment on cell proliferation and miRNA regulation. miR-520a-5p expression was extremely downregulated in capsaicin-treated cells. Repressing the level of miR-520a-5p by transient transfection with specific miRNA inhibitor oligonucleotides resulted in induced inhibition of proliferation in leukemic cells. According to bioinformatics analysis, STAT3 messenger RNA was predicted as a putative miR-520a-5p target; which was confirmed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot analysis. Cell proliferation inhibition was enhanced upon knockdown of STAT3 by RNA interference applications, but when miR-520a-5p inhibitor was additionally transfected onto STAT3 silenced cells, cell viability was dramatically decreased in leukemia cells. Finally, we observed the effects of capsaicin following miR-520a-5p inhibitor transfection upon cell proliferation, apoptosis, and STAT3 expression levels. We determined that, downregulation of miR-520a-5p affected the proliferation inhibition enhanced by capsaicin and reduced STAT3 mRNA and protein expression levels and increased apoptotic cell number. In summary, miR-520a-5p displays a therapeutic effect by targeting STAT3 and impacting the anticancer effects of capsaicin; whereas capsaicin, potentially through the miR-520a-5p/STAT3 interaction, induces apoptosis and inhibits K562 leukemic cell proliferation with need of further investigation.
MeSH term(s)	Anticarcinogenic Agents/pharmacology ; Apoptosis/drug effects ; Apoptosis/genetics ; Blotting, Western ; Capsaicin/pharmacology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cell Survival/genetics ; Dose-Response Relationship, Drug ; Down-Regulation ; Gene Expression Regulation, Leukemic ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; MicroRNAs/genetics ; RNA Interference ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Time Factors
Chemical Substances	Anticarcinogenic Agents ; MIRN520 microRNA, human ; MicroRNAs ; RNA, Messenger ; STAT3 Transcription Factor ; Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2014-05-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605825-5
ISSN	1423-0380 ; 0289-5447 ; 1010-4283
ISSN (online)	1423-0380
ISSN	0289-5447 ; 1010-4283
DOI	10.1007/s13277-014-2138-z
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Zs.A 1598: Show issues

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Article: Cytotoxicity of dentin bonding agents.

Cal, Ebru / Guneri, Pelin / Atay, Ayse / Cetintas, Vildan Bozok

General dentistry

2014 Volume 62, Issue 6, Page(s) e11–4

Abstract: This study sought to evaluate the cytotoxicity of 5 dentin bonding agents (Admira Bond, Adper Single Bond Plus, Clearfil SE Bond, Clearfil S3 Bond, and Heliobond) by XTT assay using human gingival fibroblast cells. Samples of dentin bonding agents were ... ...

Abstract	This study sought to evaluate the cytotoxicity of 5 dentin bonding agents (Admira Bond, Adper Single Bond Plus, Clearfil SE Bond, Clearfil S3 Bond, and Heliobond) by XTT assay using human gingival fibroblast cells. Samples of dentin bonding agents were prepared on a black 96-well microplate, and the cytotoxicity of each bonding material was measured every 24 hours for 7 days, then on Days 14, 21, and 28. One-way ANOVA and Bonferroni post hoc tests were used for statistical analyses. All 5 materials were evaluated as severely cytotoxic (P < 0.001) on the first day, with cell viabilities ranging from 6% to 24%. All the bonding agents showed severe cytotoxicity with viability results <10%. With the exception of Adper Single Bond Plus, toxicity continued to Day 28 for all compounds. The utmost care must be considered during the clinical utilization of dentin bonding agents to keep them within the area of restoration and prevent their contact with adjacent tissues.
MeSH term(s)	Cells, Cultured ; Dentin-Bonding Agents/toxicity ; Fibroblasts/drug effects ; Gingiva/cytology ; Gingiva/drug effects ; Humans
Chemical Substances	Dentin-Bonding Agents
Language	English
Publishing date	2014-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	603650-8
ISSN	0363-6771
ISSN	0363-6771
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Zs.B 2262: Show issues

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Article: Identification of Y chromosome microdeletions in infertile Turkish men.

Küçükaslan, Ali Şahin / Çetintaş, Vildan Bozok / Altıntaş, Raşit / Vardarlı, Aslı Tetik / Mutlu, Zeynep / Ulukuş, Murat / Semerci, Bülent / Eroğlu, Zuhal

Turkish journal of urology

2015 Volume 39, Issue 3, Page(s) 170–174

Abstract: Objective: The aim of this study was to determine the frequencies of Y chromosome microdeletions in infertile azoospermic and oligozoospermic Turkish men and in healthy control subjects.: Material and methods: Sixty-four azoospermic and 51 ... ...

Abstract	Objective: The aim of this study was to determine the frequencies of Y chromosome microdeletions in infertile azoospermic and oligozoospermic Turkish men and in healthy control subjects. Material and methods: Sixty-four azoospermic and 51 oligozoospermic patients infertile patients, and 70 healthy men who had a child without the aid of assisted reproductive technologies were included in this study. DNA was extracted from peripheral blood samples collected from the patients. Following multiplex PCR performed with 15 different primer sequences, Y chromosome AZFa, AZFb, AZFc and AZFd region microdeletions were determined by agarose gel electrophoresis. Results: Y chromosome microdeletions were detected in 8 (12.5%) patients in the azoospermia group and 3 (5.9%) patients in the oligozoospermia group. The overall frequency of Y chromosome microdeletions in all infertile cases was 9.6%. Y chromosome microdeletions were not found in the healthy control group. Among the infertile cases, there were 4 (3.48%) AZFa, 2 (1.74%) AZFb, 3 (2.61%) AZFc and 7 (6.09%) AZFd region microdeletions. Y chromosome microdeletions were not found among healthy men in the control group. Conclusion: The presence of Y chromosome microdeletions among azoospermic and oligozoospermic infertile males suggests that routine genetic testing and genetic counseling prior to the use of assisted reproduction techniques are necessary.
Language	English
Publishing date	2015-06-01
Publishing country	Turkey
Document type	Journal Article
ISSN	2149-3235
ISSN	2149-3235
DOI	10.5152/tud.2013.035
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Article ; Online: Two newly discovered variations of the plasminogen activator inhibitor 1 gene in 3 Turkish cases.

Cetintas, Vildan Bozok / Kosova, Buket / Karaca, Emin / Bulut, Gulcan / Cekdemir, Demet

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis

2012 Volume 18, Issue 3, Page(s) 327–330

MeSH term(s)	Adult ; Female ; Humans ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1/genetics ; Point Mutation ; Turkey
Chemical Substances	Plasminogen Activator Inhibitor 1 ; SERPINE1 protein, human
Language	English
Publishing date	2012-06
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	1237357-6
ISSN	1938-2723 ; 1076-0296
ISSN (online)	1938-2723
ISSN	1076-0296
DOI	10.1177/1076029611424577
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Zs.A 4370: Show issues

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Article ; Online: From a molecular biological viewpoint, does endothelin type A receptor antagonist therapy reduce diabetes-induced testicular damage in rats?

Kosova, Buket / Cetintaş, Vildan Bozok / Yavaşoğlu, Altuğ / Altay, Barış / Aktuğ, Hüseyin

Urology

2011 Volume 77, Issue 1, Page(s) 250.e7–13

Abstract: Objectives: To evaluate the therapeutic effects of a selective endothelin type A receptor antagonist (ERA-A) on testis of streptozotocin (STZ)-induced diabetic rats.: Methods: Eighty rats were analyzed in 4 groups: healthy controls, diabetic rats, ... ...

Abstract	Objectives: To evaluate the therapeutic effects of a selective endothelin type A receptor antagonist (ERA-A) on testis of streptozotocin (STZ)-induced diabetic rats. Methods: Eighty rats were analyzed in 4 groups: healthy controls, diabetic rats, diabetic rats treated with ERA-A, and healthy rats treated with ERA-A. Diabetes was induced in 40 rats by a single intraperitoneal injection of STZ and followed for 2 months. A total of 20 diabetic and 20 healthy rats were also intravenously treated with ERA-A at days 7 and 15. The remaining untreated healthy rats served as controls. Blood glucose levels of ≥ 250 mg/dL were considered to indicate diabetes and were measured at the end of the second month. Formalin-fixed paraffin-embedded testis tissue sections were analyzed after staining with hematoxylin and eosin or specific antibodies for apoptotic markers. mRNA expressions of genes involved in the apoptotic pathway or spermatogenesis were evaluated by real-time reverse transcription-polymerase chain reaction. Results: Major therapeutic effects of ERA-A could be achieved for damages caused by oxidative stress. Although a decrease in apoptotic cell death could be detected, no statistically meaningful results could be obtained for the duration of spermatogenesis. Conclusions: ERA-A could prevent germ cell death by apoptosis and testicular damage in diabetic rats.
MeSH term(s)	Animals ; Diabetes Complications/pathology ; Diabetes Complications/physiopathology ; Diabetes Complications/prevention & control ; Endothelin A Receptor Antagonists ; Male ; Molecular Biology ; Peptides, Cyclic/therapeutic use ; Rats ; Spermatogenesis ; Testicular Diseases/pathology ; Testicular Diseases/physiopathology ; Testicular Diseases/prevention & control
Chemical Substances	Endothelin A Receptor Antagonists ; Peptides, Cyclic ; cyclo(Trp-Asp-Pro-Val-Leu) (S2A8YZM151)
Language	English
Publishing date	2011-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	192062-5
ISSN	1527-9995 ; 0090-4295
ISSN (online)	1527-9995
ISSN	0090-4295
DOI	10.1016/j.urology.2010.04.052
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