PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article CRISPR/Cas9-mediated Metabolic Engineering of Endophytic Pseudomonas Loganensis Sp. Nov. for the Production of Nutritionally Valuable Carotenoids(American Chemical Society, 2026-01-02) Arslansoy, N.; Karaman, M.Z.; Fidan, O.Carotenoids with significant nutritional and antioxidant properties have been widely utilized in the food, feed, pharmaceutical, and cosmetic industries. They improve the nutritional value of foodstuffs and have been used as natural food colorants. However, their current supply chain is mainly dependent on extraction from plants and chemical synthesis, both of which have bottlenecks, including environmental concerns, toxicity, and allergenicity. To address global demand for sustainable and environmentally friendly production of nutrients, we engineered the endophytic Pseudomonas loganensis sp. nov. as a niche microbial chassis for nutritionally valuable carotenoid production. Using CRISPR-Cas9, we knocked out key carotenogenic genes to construct strains capable of producing zeaxanthin, lycopene, and β-carotene. Additionally, an overexpression plasmid was introduced to produce astaxanthin. HPLC analysis confirmed the successful production of four target carotenoids. The culture conditions and media compositions were optimized using response surface methodology, resulting in a ∼5-fold increase in the titers of zeaxanthin (13.4 mg/L), lycopene (9.67 mg/L), and β-carotene (23.53 mg/L), and a ∼12-fold increase in astaxanthin titer (1 mg/L) compared to LB medium without optimization. Our results indicate the potential of endophytic bacteria as a microbial chassis for carotenoid bioproduction, underscoring the potential of synthetic biology to contribute to global efforts toward nutritional security and sustainable food systems. © 2026 The Authors. Published by American Chemical SocietyArticle Citation - WoS: 43Citation - Scopus: 49The Pleiotropic Effects of Fisetin and Hesperetin on Human Acute Promyelocytic Leukemia Cells Are Mediated Through Apoptosis, Cell Cycle Arrest, and Alterations in Signaling Networks(Sage Publications Ltd, 2015-06-17) Adan, Aysun; Baran, YusufFisetin and hesperetin, flavonoids from various plants, have several pharmaceutical activities including antioxidative, anti-inflammatory, and anticancer effects. However, studies elucidating the role and the mechanism(s) of action of fisetin and hesperetin in acute promyelocytic leukemia are absent. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by fisetin and hesperetin on human HL60 acute promyelocytic leukemia cells. The viability of HL60 cells was evaluated using the MTT assay, apoptosis by annexin V/propidium iodide (PI) staining and cell cycle distribution using flow cytometry, and changes in caspase-3 enzyme activity and mitochondrial transmembrane potential. Moreover, we performed whole-genome microarray gene expression analysis to reveal genes affected by fisetin and hesperetin that can be important for developing of future targeted therapy. Based on data obtained from microarray analysis, we also described biological networks modulated after fisetin and hesperetin treatment by KEGG and IPA analysis. Fisetin and hesperetin treatment showed a concentration- and time-dependent inhibition of proliferation and induced G2/M arrest for both agents and G0/G1 arrest for hesperetin at only the highest concentrations. There was a disruption of mitochondrial membrane potential together with increased caspase-3 activity. Furthermore, fisetin- and hesperetin-triggered apoptosis was confirmed by annexin V/PI analysis. The microarray gene profiling analysis revealed some important biological pathways including mitogen-activated protein kinases (MAPK) and inhibitor of DNA binding (ID) signaling pathways altered by fisetin and hesperetin treatment as well as gave a list of genes modulated a parts per thousand yen2-fold involved in cell proliferation, cell division, and apoptosis. Altogether, data suggested that fisetin and hesperetin have anticancer properties and deserve further investigation.Correction Citation - WoS: 1Citation - Scopus: 1The Influence of Cement Kiln Dust on Strength and Durability Properties of Cement-Based Systems(Springer Heidelberg, 2022-06-15) Hakkomaz, Hadiye; Yorulmaz, Hediye; Durak, Ugur; Ilkentapar, Serhan; Karahan, Okan; Atis, Cengiz DuranArticle Citation - WoS: 15Citation - Scopus: 11T Cells in Tumor Microenvironment(Springer, 2015-10-18) Kiraz, Yagmur; Baran, Yusuf; Nalbant, AytenTumors progress in a specific area, which supports its development, spreading or shrinking in time with the presence of different factors that effect the fate of the cancer cells. This specialized site is called "tumor microenvironment" and has a composition of heterogenous materials. The immune cells are also residents of this stromal, cancerous, and inflammatory environment, and their types, densities, or functional differences are one of the key factors that mediate the fate of a tumor. T cells as a vital part of the immune system also are a component of tumor microenvironment, and their roles have been elucidated in many studies. In this review, we focused on the immune system components by focusing on T cells and detailed T helper cell subsets in tumor microenvironment and how their behaviors affect either the tumor or the patient's outcome.Article Citation - WoS: 29Citation - Scopus: 30Revealing Genome-Wide mRNA and MicroRNA Expression Patterns in Leukemic Cells Highlighted HSA-MIR as a Tumor Suppressor for Regain of Chemotherapeutic Imatinib Response due to Targeting STAT5A(Sage Publications Ltd, 2015-05-08) Kaymaz, Burcin Tezcanli; Gunel, Nur Selvi; Ceyhan, Metin; Cetintas, Vildan Bozok; Ozel, Buket; Yandim, Melis Kartal; Can, Buket KosovaBCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide MicroRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 mu M) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNAArticle Citation - Scopus: 25Recursive Cluster Elimination Based Rank Function (SVM-RCE-R) Implemented in KNIME(F1000 Research Ltd, 2021-01-05) Yousef, Malik; Bakir-Güngör, Burcu; Jabeer, Amhar; Göy, Gökhan; Qureshi, Rehman A.; C Showe, Louise; C. Showe, LouiseIn our earlier study, we proposed a novel feature selection approach, Recursive Cluster Elimination with Support Vector Machines (SVM-RCE) and implemented this approach in Matlab. Interest in this approach has grown over time and several researchers have incorporated SVM-RCE into their studies, resulting in a substantial number of scientific publications. This increased interest encouraged us to reconsider how feature selection, particularly in biological datasets, can benefit from considering the relationships of those genes in the selection process, this led to our development of SVM-RCE-R. SVM-RCE-R, further enhances the capabilities of SVM-RCE by the addition of a novel user specified ranking function. This ranking function enables the user to stipulate the weights of the accuracy, sensitivity, specificity, f-measure, area under the curve and the precision in the ranking function This flexibility allows the user to select for greater sensitivity or greater specificity as needed for a specific project. The usefulness of SVM-RCE-R is further supported by development of the maTE tool which uses a similar approach to identify MicroRNA (miRNA) targets. We have also now implemented the SVM-RCE-R algorithm in Knime in order to make it easier to applyThe use of SVM-RCE-R in Knime is simple and intuitive and allows researchers to immediately begin their analysis without having to consult an information technology specialist. The input for the Knime implemented tool is an EXCEL file (or text or CSV) with a simple structure and the output is also an EXCEL file. The Knime version also incorporates new features not available in SVM-RCE. The results show that the inclusion of the ranking function has a significant impact on the performance of SVM-RCE-R. Some of the clusters that achieve high scores for a specified ranking can also have high scores in other metrics. © 2021 Elsevier B.V., All rights reserved.Article Citation - WoS: 70Citation - Scopus: 78Prophylactic and Therapeutic Roles of Oleanolic Acid and Its Derivatives in Several Diseases(Baishideng Publishing Group inc, 2020-05-26) Sen, AlaattinOleanolic acid (OA) and its derivatives are widely found in diverse plants and are naturally effective pentacyclic triterpenoid compounds with broad prophylactic and therapeutic roles in various diseases such as ulcerative colitis, multiple sclerosis, metabolic disorders, diabetes, hepatitis and different cancers. This review assembles and presents the latestin vivoreports on the impacts of OA and OA derivatives from various plant sources and the biological mechanisms of OA activities. Thus, this review presents sufficient data proposing that OA and its derivatives are potential alternative and complementary therapies for the treatment and management of several diseases.Article Citation - WoS: 17Citation - Scopus: 18Obesity Induced by High-Fat Diet Is Associated With Critical Changes in Biological and Molecular Functions of Mesenchymal Stromal Cells Present in Visceral Adipose Tissue(Impact Journals LLC, 2020-12-27) Acar, Mustafa Burak; Ayaz-Guner, Serife; Di Bernardo, Giovanni D.; Guner, Hüseyin; Murat, Ayşegül; Peluso, G. F.; Galderisi, UmbertoThe mesenchymal stromal cells (MSCs) residing within the stromal component of visceral adipose tissue appear to be greatly affected by obesity, with impairment of their functions and presence of senescence. To gain further insight into these phenomena, we analyzed the changes in total proteome content and secretome of mouse MSCs after a high-fat diet (HFD) treatment compared to a normal diet (ND). In healthy conditions, MSCs are endowed with functions mainly devoted to vesicle trafficking. These cells have an immunoregulatory role, affecting leukocyte activation and migration, acute inflammation phase response, chemokine signaling, and platelet activities. They also present a robust response to stress. We identified four signaling pathways (TGF-β, VEGFR2, HMGB1, and Leptin) that appear to govern the cells’ functions. In the obese mice, MSCs showed a change in their functions. The immunoregulation shifted toward pro-inflammatory tasks with the activation of interleukin-1 pathway and of Granzyme A signaling. Moreover, the methionine degradation pathway and the processing of capped intronless pre-mRNAs may be related to the inflammation process. The signaling pathways we identified in ND MSCs were replaced by MET, WNT, and FGFR2 signal transduction, which may play a role in promoting inflammation, cancer, and aging © 2024 Elsevier B.V., All rights reserved.Article Citation - WoS: 496Citation - Scopus: 550Major Apoptotic Mechanisms and Genes Involved in Apoptosis(Sage Publications Ltd, 2016-04-09) Kiraz, Yagmur; Adan, Aysun; Yandim, Melis Kartal; Baran, Yusuf; Kartal Yandim, MelisAs much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.Article Citation - WoS: 4Citation - Scopus: 4Effects of COVID-19 on Adolescent Mental Health and Internet Use by Ethnicity and Gender: A Mixed-Method Study(MDPI, 2022-07-22) Kaya, M. Siyabend; McCabe, CiaraEvidence suggests that mental health problems in young people have been exacerbated by COVID-19, possibly related to a lack of social connection. Young people report using the internet for connecting with their peers and mental health support. However, how they may have used the internet for support during COVID-19 is not clear. We wanted to know how mood and internet use may have changed in young people during COVID-19 and if this was different for those with and without depression symptoms. 108 adolescents were recruited. Participants with high and low levels of depressive symptomatology answered questions about their mood, internet use, loneliness and life satisfaction during July and August 2020. We found that the high depression group reported significantly more loneliness and less life satisfaction than the low depression group. We found that most young people used the internet for mental health information during COVID-19 but that the high depression group used the internet more for mental health information than the low depression group. The high depression group also had a worsening of mood compared to the low depression group during COVID-19. We found that Black, Asian and Minority Ethnic participants reported increased use of the internet compared to White participants during COVID-19 and that the role of the family facilitated coping during COVID-19 for some adolescents, but for others, it made the lockdown more difficult. Finally, we found that adolescents perceived school anxiety as stressful as COVID-19. To conclude this study supports the use of the internet as a way to help young people with mental health challenges. It also suggests that the internet is a way to help young people from ethnic minorities, who otherwise might be hard to reach, during challenging times. This study also shows that supportive family units can be important during times of stress for young people and that school anxiety is a major issue for young people in today's society even outside of the pandemic.