Browsing by Author "Ozcan, Servet"

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Capturing B type acute lymphoblastic leukemia cells using two types of antibodies
(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2019) Icoz, Kutay; Gercek, Tayyibe; Murat, Aysegul; Ozcan, Servet; Unal, Ekrem; AGÜ, Mühendislik Fakültesi, Elektrik & Elektronik Mühendisliği Bölümü;
One way to monitor minimal residual disease (MRD) is to screen cells for multiple surface markers using flow cytometry. In order to develop an alternative microfluidic based method, isolation of B type acute lymphoblastic cells using two types of antibodies should be investigated. The immunomagnetic beads coated with various antibodies are used to capture the B type acute lymphoblastic cells. Single beads, two types of beads and surface immobilized antibody were used to measure the capture efficiency. Both micro and nanosize immunomagnetic beads can be used to capture B type acute lymphoblastic cells with a minimum efficiency of 94% and maximum efficiency of 98%. Development of a microfluidic based biochip incorporating immunomagnetic beads and surface immobilized antibodies for monitoring MRD can be an alternative to current cost and time inefficient laboratory methods. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2737, 2019
A comparative study on normal and obese mice indicates that the secretome of mesenchymal stromal cells is influenced by tissue environment and physiopathological conditions
(BMC, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, 2020) Ayaz-Guner, Serife; Alessio, Nicola; Acar, Mustafa B.; Aprile, Domenico; Ozcan, Servet; Di Bernardo, Giovanni; Peluso, Gianfranco; Galderisi, Umberto; 0000-0002-1052-0961; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü
Background: The term mesenchymal stromal cells (MSCs) designates an assorted cell population comprised of stem cells, progenitor cells, fibroblasts, and stromal cells. MSCs contribute to the homeostatic maintenance of many organs through paracrine and long-distance signaling. Tissue environment, in both physiological and pathological conditions, may affect the intercellular communication of MSCs. Methods: We performed a secretome analysis of MSCs isolated from subcutaneous adipose tissue (sWAT) and visceral adipose tissue (vWAT), and from bone marrow (BM), of normal and obese mice. Results: The MSCs isolated from tissues of healthy mice share a common core of released factors: components of cytoskeletal and extracellular structures; regulators of basic cellular functions, such as protein synthesis and degradation; modulators of endoplasmic reticulum stress; and counteracting oxidative stress. It can be hypothesized that MSC secretome beneficially affects target cells by the horizontal transfer of many released factors. Each type of MSC may exert specific signaling functions, which could be determined by looking at the many factors that are exclusively released from every MSC type. The vWAT-MSCs release factors that play a role in detoxification activity in response to toxic substances and drugs. The sWAT-MSC secretome contains proteins involved in in chondrogenesis, osteogenesis, and angiogenesis. Analysis of BM-MSC secretome revealed that these cells exert a signaling function by remodeling extracellular matrix structures, such as those containing glycosaminoglycans. Obesity status profoundly modified the secretome content of MSCs, impairing the above-described activity and promoting the release of inflammatory factors. Conclusion: We demonstrated that the content of MSC secretomes depends on tissue microenvironment and that pathological condition may profoundly alter its composition.
Immunomagnetic separation of B type acute lymphoblastic leukemia cells from bone marrow with flow cytometry validation and microfluidic chip measurements
(TAYLOR & FRANCIS INC, 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA, 2020) Icoz, Kutay; Eken, Ahmet; Cinar, Suzan; Murat, Aysegul; Ozcan, Servet; Unal, Ekrem; Deniz, Gunnur; 0000-0002-8330-7010; 0000-0002-0947-6166; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
In order to detect the blast cells from bone marrow of patients, one strategy is to first isolate the cells using immunomagnetic beads. The aim of this study was to report the experimental results of the immunomagnetic separation efficiency of the blast cells from bone marrow of pediatric leukemia patients. To test the efficiency of immunomagnetic separation, flow cytometry measurements at critical steps were performed. We here reported 94.5% capture efficiency for CD10 nano beads. Patients samples were also analyzed with a microfluidic chip to test the feasibility for further developments.
Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells
(FRONTIERS MEDIA SAAVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE CH-1015, SWITZERLAND, 2021) Acar, Mustafa Burak; Ayaz-Guner, Serife; Gunaydin, Zeynep; Karakukcu, Musa; Peluso, Gianfranco; Di Bernardo, Giovanni; Ozcan, Servet; Galderisi, Umberto; 0000-0002-1052-0961; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Ayaz-Guner, Serife
Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs' intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.
A subtractive proteomics approach for the identification of immunodominant Acinetobacter baumannii vaccine candidate proteins
(FRONTIERS MEDIA SA, 2022) Acar, Mustafa Burak; Ayaz-Guner, Serife; Guner, Huseyin; Dinc, Gokcen; Kilic, Aysegul Ulu; Doganay, Mehmet; Ozcan, Servet; 0000-0002-0220-5224; 0000-0002-1052-0961; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Ayaz-Guner, Serife; Guner, Huseyin
Background: Acinetobacter baumannii is one of the most life-threatening multidrug-resistant pathogens worldwide. Currently, 50%–70% of clinical isolates of A. baumannii are extensively drug-resistant, and available antibiotic options against A. baumannii infections are limited. There is still a need to discover specific de facto bacterial antigenic proteins that could be effective vaccine candidates in human infection. With the growth of research in recent years, several candidate molecules have been identified for vaccine development. So far, no public health authorities have approved vaccines against A. baumannii. Methods: This study aimed to identify immunodominant vaccine candidate proteins that can be immunoprecipitated specifically with patients’ IgGs, relying on the hypothesis that the infected person’s IgGs can capture immunodominant bacterial proteins. Herein, the outer-membrane and secreted proteins of sensitive and drug-resistant A. baumannii were captured using IgGs obtained from patient and healthy control sera and identified by Liquid Chromatography- Tandem Mass Spectrometry (LC-MS/MS) analysis. Results: Using the subtractive proteomic approach, we determined 34 unique proteins captured only in drug-resistant A. baumannii strain via patient sera. After extensively evaluating the predicted epitope regions, solubility, transverse membrane characteristics, and structural properties, we selected several notable vaccine candidates. Conclusion: We identified vaccine candidate proteins that triggered a de facto response of the human immune system against the antibiotic-resistant A. Frontiers in Immunology 01 frontiersin.org OPEN ACCESS EDITED BY Saeed Khalili, Shahid Rajaee Teacher Training University, Iran REVIEWED BY Abbas Yadegar, Shahid Beheshti University of Medical Sciences, Iran Prince Sharma, Panjab University, India Seung Il Kim, Korea Basic Science Institute (KBSI), South Korea *CORRESPONDENCE Servet Özcan ozcan@erciyes.edu.tr SPECIALTY SECTION This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology RECEIVED 23 July 2022 ACCEPTED 10 October 2022 PUBLISHED 10 November 2022 CITATION Acar MB, Ayaz-Güner S¸, Güner H, Dinc¸ G, Ulu Kılıc¸ A, Dog˘ anay M and Özcan S (2022) A subtractive proteomics approach for the identification of immunodominant Acinetobacter baumannii vaccine candidate proteins. Front. Immunol. 13:1001633. doi: 10.3389/fimmu.2022.1001633 COPYRIGHT © 2022 Acar, Ayaz-Güner, Güner, Dinc¸, Ulu Kılıc¸, Dog˘ anay and Özcan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Original Research PUBLISHED 10 November 2022 DOI 10.3389/fimmu.2022.1001633 baumannii. Precipitation of bacterial proteins via patient immunoglobulins was a novel approach to identifying the proteins that could trigger a response in the patient immune system.
Why Do Muse Stem Cells Present an Enduring Stress Capacity? Hints from a Comparative Proteome Analysis
(MDPIST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, 2021) Acar, Mustafa B.; Aprile, Domenico; Ayaz-Guner, Serife; Guner, Huseyin; Tez, Coskun; Di Bernardo, Giovanni; Peluso, Gianfranco; Ozcan, Servet; Galderisi, Umberto; 0000-0002-1052-0961; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Ayaz-Guner, Serife; Guner, Huseyin
Muse cells are adult stem cells that are present in the stroma of several organs and possess an enduring capacity to cope with endogenous and exogenous genotoxic stress. In cell therapy, the peculiar biological properties of Muse cells render them a possible natural alternative to mesenchymal stromal cells (MSCs) or to in vitro-generated pluripotent stem cells (iPSCs). Indeed, some studies have proved that Muse cells can survive in adverse microenvironments, such as those present in damaged/injured tissues. We performed an evaluation of Muse cells' proteome under basic conditions and followed oxidative stress treatment in order to identify ontologies, pathways, and networks that can be related to their enduring stress capacity. We executed the same analysis on iPSCs and MSCs, as a comparison. The Muse cells are enriched in several ontologies and pathways, such as endosomal vacuolar trafficking related to stress response, ubiquitin and proteasome degradation, and reactive oxygen scavenging. In Muse cells, the protein-protein interacting network has two key nodes with a high connectivity degree and betweenness: NFKB and CRKL. The protein NFKB is an almost-ubiquitous transcription factor related to many biological processes and can also have a role in protecting cells from apoptosis during exposure to a variety of stressors. CRKL is an adaptor protein and constitutes an integral part of the stress-activated protein kinase (SAPK) pathway. The identified pathways and networks are all involved in the quality control of cell components and may explain the stress resistance of Muse cells.