PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
Browse
13 results
Search Results
Now showing 1 - 10 of 13
Article Citation - WoS: 8Citation - Scopus: 8Canonical Wnt and Tgf-β/Bmp Signaling Enhance Melanocyte Regeneration but Suppress Invasiveness, Migration, and Proliferation of Melanoma Cells(Frontiers Media S.A., 2023) Katkat, Esra; Demirci, Yeliz; Heger, Guillaume; Karagülle, Doğa; Papatheodorou, Irene; Brazma, Alvis; Özhan, GüneşMelanoma is the deadliest form of skin cancer and develops from the melanocytes that are responsible for the pigmentation of the skin. The skin is also a highly regenerative organ, harboring a pool of undifferentiated melanocyte stem cells that proliferate and differentiate into mature melanocytes during regenerative processes in the adult. Melanoma and melanocyte regeneration share remarkable cellular features, including activation of cell proliferation and migration. Yet, melanoma considerably differs from the regenerating melanocytes with respect to abnormal proliferation, invasive growth, and metastasis. Thus, it is likely that at the cellular level, melanoma resembles early stages of melanocyte regeneration with increased proliferation but separates from the later melanocyte regeneration stages due to reduced proliferation and enhanced differentiation. Here, by exploiting the zebrafish melanocytes that can efficiently regenerate and be induced to undergo malignant melanoma, we unravel the transcriptome profiles of the regenerating melanocytes during early and late regeneration and the melanocytic nevi and malignant melanoma. Our global comparison of the gene expression profiles of melanocyte regeneration and nevi/melanoma uncovers the opposite regulation of a substantial number of genes related to Wnt signaling and transforming growth factor beta (TGF-beta)/(bone morphogenetic protein) BMP signaling pathways between regeneration and cancer. Functional activation of canonical Wnt or TGF-beta/BMP pathways during melanocyte regeneration promoted melanocyte regeneration but potently suppressed the invasiveness, migration, and proliferation of human melanoma cells in vitro and in vivo. Therefore, the opposite regulation of signaling mechanisms between melanocyte regeneration and melanoma can be exploited to stop tumor growth and develop new anti-cancer therapies.Article Citation - WoS: 3Citation - Scopus: 3A Subtractive Proteomics Approach for the Identification of Immunodominant Acinetobacter Baumannii Vaccine Candidate Proteins(Frontiers Media S.A., 2022) Acar, Mustafa Burak; Ayaz Güner, Şerife; Güner, Hüseyin; Dinç, Gökçen; Ulu Kılıç, Ayşegül; Doğanay, Mehmet; Özcan, ServetBackground: 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. 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.Article Citation - WoS: 14Citation - Scopus: 16Plaqview 2.0: a Comprehensive Web Portal for Cardiovascular Single-Cell Genomics(Frontiers Media S.A., 2022) Ma, Wei Feng; Turner, Adam W.; Gancayco, Christina; Wong, Doris; Song, Yipei; Mosquera, Jose Verdezoto; Auguste, Gaëlle; Hodonsky, Chani J.; Prabhakar, Ajay; Ekiz, Hüseyin Atakan; van der Laan, Sander W.; Miller, Clint L.Single-cell RNA-seq (scRNA-seq) is a powerful genomics technology to interrogate the cellular composition and behaviors of complex systems. While the number of scRNA-seq datasets and available computational analysis tools have grown exponentially, there are limited systematic data sharing strategies to allow rapid exploration and re-analysis of single-cell datasets, particularly in the cardiovascular field. We previously introduced PlaqView, an open-source web portal for the exploration and analysis of published atherosclerosis single-cell datasets. Now, we introduce PlaqView 2.0 (www.plaqview.com), which provides expanded features and functionalities as well as additional cardiovascular single-cell datasets. We showcase improved PlaqView functionality, backend data processing, user-interface, and capacity. PlaqView brings new or improved tools to explore scRNA-seq data, including gene query, metadata browser, cell identity prediction, ad hoc RNA-trajectory analysis, and drug-gene interaction prediction. PlaqView serves as one of the largest central repositories for cardiovascular single-cell datasets, which now includes data from human aortic aneurysm, gene-specific mouse knockouts, and healthy references. PlaqView 2.0 brings advanced tools and high-performance computing directly to users without the need for any programming knowledge. Lastly, we outline steps to generalize and repurpose PlaqView's framework for single-cell datasets from other fields.Article Citation - WoS: 6Citation - Scopus: 6Analysis of Brain Lipids in the Early-Onset Tay–sachs Disease Mouse Model With the Combined Deficiency of Β-Hexosaminidase a and Neuraminidase 3(Frontiers Media S.A., 2022) Can, Melike; Şengül, Tuğçe; Akyıldız Demir, Seçil; İnci, Orhan K.; Basırlı, Hatice Hande; Seyrantepe, VolkanTay–Sachs disease is an autosomal recessively inherited lysosomal storage disease that results from loss-of-function mutations in the HEXA gene coding βhexosaminidase A. HEXA gene deficiency affects the central nervous system owing to GM2 ganglioside accumulation in lysosomes resulting in progressive neurodegeneration in patients. We recently generated a novel mice model with a combined deficiency of βhexosaminidase A and neuraminidase 3 (Hexa−/−Neu3−/−) that mimics both the neuropathological and clinical abnormalities of early-onset Tay–Sachs disease. Here, we aimed to explore the secondary accumulation of lipids in the brain of Hexa−/ −Neu3−/− mice.Article Citation - WoS: 9Citation - Scopus: 11Mir-Aculous New Avenues for Cancer Immunotherapy(Frontiers Media S.A., 2022) Tang, William W.; Bauer, Kaylyn M.; Barba, Cindy; Ekiz, Hüseyin Atakan; O’Connell, Ryan M.The rising toll of cancer globally necessitates ingenuity in early detection and therapy. In the last decade, the utilization of immune signatures and immune-based therapies has made significant progress in the clinic; however, clinical standards leave many current and future patients without options. Non-coding RNAs, specifically microRNAs, have been explored in pre-clinical contexts with tremendous success. MicroRNAs play indispensable roles in programming the interactions between immune and cancer cells, many of which are current or potential immunotherapy targets. MicroRNAs mechanistically control a network of target genes that can alter immune and cancer cell biology. These insights provide us with opportunities and tools that may complement and improve immunotherapies. In this review, we discuss immune and cancer cell–derived miRNAs that regulate cancer immunity and examine miRNAs as an integral part of cancer diagnosis, classification, and therapy.Article Citation - WoS: 8Citation - Scopus: 10Interaction With Fungi Promotes the Accumulation of Specific Defense Molecules in Orchid Tubers and May Increase the Value of Tubers for Biotechnological and Medicinal Applications: the Case Study of Interaction Between Dactylorhiza Sp. and Tulasnella Calospora(Frontiers Media S.A., 2022) Hampejsová, Romana; Berka, Miroslav; Berková, Veronika; Jersáková, Jana; Domkářová, Jaroslava; von Rundstedt, Friederike; Frary, Anne; Saiz-Fernández, Iñigo; Brzobohatý, Břetislav; Černý, MartinTerrestrial orchids can form tubers, organs modified to store energy reserves. Tubers are an attractive source of nutrients, and salep, a flour made from dried orchid tubers, is the source of traditional beverages. Tubers also contain valuable secondary metabolites and are used in traditional medicine. The extensive harvest of wild orchids is endangering their populations in nature; however, orchids can be cultivated and tubers mass-produced. This work illustrates the importance of plant-fungus interaction in shaping the content of orchid tubers in vitro. Orchid plants of Dactylorhiza sp. grown in asymbiotic culture were inoculated with a fungal isolate from Tulasnella calospora group and, after 3 months of co-cultivation, tubers were analyzed. The fungus adopted the saprotrophic mode of life, but no visible differences in the morphology and biomass of the tubers were detected compared to the mock-treated plants. To elucidate the mechanisms protecting the tubers against fungal infestation, proteome, metabolome, and lipidome of tubers were analyzed. In total, 1,526, 174, and 108 proteins, metabolites, and lipids were quantified, respectively, providing a detailed snapshot of the molecular process underlying plant-microbe interaction. The observed changes at the molecular level showed that the tubers of inoculated plants accumulated significantly higher amounts of antifungal compounds, including phenolics, alkaloid Calystegine B2, and dihydrophenanthrenes. The promoted antimicrobial effects were validated by observing transient inhibition of Phytophthora cactorum growth. The integration of omics data highlighted the promotion of flavonoid biosynthesis, the increase in the formation of lipid droplets and associated production of oxylipins, and the accumulation of auxin in response to T. calospora. Taken together, these results provide the first insights into the molecular mechanisms of defense priming in orchid tubers and highlight the possible use of fungal interactors in biotechnology for the production of orchid secondary metabolites.Article Citation - WoS: 7Citation - Scopus: 8Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-Coding Rna as a Modulator of Proliferation and Metastasis in Hela Cells(Frontiers Media S.A., 2021) Gürer, Dilek Cansu; Erdoğan, İpek; Ahmadov, Ulvi; Başol, Merve; Sweef, Osama; Çakan Akdoğan, Gülçin; Akgül, BünyaminCisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this study, we used a transcriptomics approach to profile lncRNAs in cisplatin-treated HeLa cells, which resulted in identification of 10,214 differentially expressed lncRNAs, of which 2,500 were antisense lncRNAs. For functional analyses, we knocked down one of the cisplatin inducible lncRNAs, death receptor 5 antisense (DR5-AS) lncRNA, which resulted in a morphological change in HeLa cell shape without inducing any cell death. A second round of transcriptomics-based profiling revealed differential expression of genes associated with immune system, motility and cell cycle in DR5-AS knockdown HeLa cells. Cellular analyses showed that DR5-AS reduced cell proliferation and caused a cell cycle arrest at S and G2/M phases. Moreover, DR5-AS knockdown reduced the invasive capacity of HeLa cells in zebrafish xenograft model. These results suggest that cisplatin-mediated pleiotropic effects, such as reduction in cell proliferation, metastasis and cell cycle arrest, may be mediated by lncRNAs. © Copyright © 2021 Gurer, Erdogan, Ahmadov, Basol, Sweef, Cakan-Akdogan and Akgül.Article Citation - WoS: 22Citation - Scopus: 24Conversion of Biomass To Organic Acids by Liquefaction Reactions Under Subcritical Conditions(Frontiers Media S.A., 2020) Yüksel Özşen, AslıRecently, liquefaction of biomass in subcritical water to convert it into value-added substances has been broadly attracting attention. However, there is a gap in literature about the levulinic acid, which is a high worth substance, production from biomass using subcritical water. As a green chemistry approach, decomposition of biomass could be obtained using subcritical water effectively. In this case, water uses as a solvent so that it gives a possibility to take place a reaction for the decomposition of biomass. Subcritical water, which liquid water and its temperature is higher than the normal boiling point of water, has higher ion product as well as higher concentrations of H+ and OH- ions. Additionally, it has high diffusivity, low viscosity and much lower dielectric constant. For instance, whereas dielectric constant of subcritical water is 80 at 298 K, it is 2 at 673 K. The point of this research paper is to assess the impacts of different reaction parameters on cellulose conversion as the principle segment of lignocellulosic biomasses for the production of value-added chemicals, particularly levulinic acid. Hazelnut shell waste was chosen as model biomass since hazelnut is a standout amongst the most cultivated agricultural crops in Turkey. Besides, Turkey provide 70% of the world's total hazelnut production. It was found that as reaction temperature increases, a considerable improvement on the amount of formed levulinic acid and conversion of hazelnut shell was observed. For instance, when the reaction temperature, time and acid concentration were 280 degrees C, 120 min and 50 mM, respectively, levulinic acid yield and conversion of hazelnut shell were found as 13.05 and 65.40%, respectively. Addition of H2SO4 enhanced the production of levulinic acid from waste hazelnut shell. Another method which is hybrid process could be used to produce value-added chemicals from lignocellulosic biomass. Hybrid process basically combines hydrolysis and electrolysis in subcritical water. Subcritical water has much lower dielectric constant than liquid water at ambient temperature. So, it was claimed that if constant current was applied to the reaction medium through specially designed electrodes in subcritical water environment, electrolysis could alter the hydrolysis reaction of cellulose in a way of protonation of intra-and inter-molecular hydrogen bonding around anode and as a result electrolysis in subcritical water could decrease necessary thermal energy to hydrolyze the beta(1-4) glycosidic linkage. Therefore, we developed a green hybrid process by combining hydrolysis and electrolysis in subcritical water without using any toxic, organic solvents and catalyst. Effects of especially applied current and temperature on the product distribution and conversions of cellulose were revealed and hydrothermal electrolysis reaction pathway of cellulose was proposed. The significance of the interaction indicated that, applied voltage had major impact on cellulose hydrolysis. Maximum cellulose conversion (82%) was achieved at 230 degrees C and 180 min of reaction time in 25 mM of H2SO4. Application of 8.0 V of applied voltage to the reaction medium at reaction temperature of 230 degrees C increased the TOC conversion (50.3%) with acid concentration of 25 mM in comparison with current-free experiments. Thus, the idea of electrochemically generated acid layer due to the dissociation of water around anode is supported. As future perspective, the output of the study gave an idea about converting cellulose and various biomass wastes, which may have high cellulose, content and led the way in obtaining valuable chemicals from no utilized real biomass sources such as hazelnut shell waste. The studies with other biomasses are undergoing.Article Citation - WoS: 28Citation - Scopus: 31Lysosomal Cathepsin a Plays a Significant Role in the Processing of Endogenous Bioactive Peptides(Frontiers Media S.A., 2016) Timur, Zehra Kevser; Akyıldız Demir, Seçil; Seyrantepe, VolkanLysosomal serine carboxypeptidase Cathepsin A (CTSA) is a multifunctional enzyme with distinct protective and catalytic function. CTSA present in the lysosomal multienzyme complex to facilitate the correct lysosomal routing, stability and activation of with beta-galactosidase and alpha-neuraminidase. Beside CTSA has role in inactivation of bioactive peptides including bradykinin, substances P, oxytocin, angiotensin I and endothelin-I by cleavage of 1 or 2 amino acid(s) from C-terminal ends. In this study, we aimed to elucidate the regulatory role of CTSA on bioactive peptides in knock-in mice model of CTSA(S190A). We investigated the level of bradykinin, substances P, oxytocin, angiotensin I and endothelin-I in the kidney, liver, lung, brain and serum from CTSA(S190A) mouse model at 3- and 6-months of age. Our results suggest CTSA selectively contributes to processing of bioactive peptides in different tissues from CTSA(S190A) mice compared to age matched WT mice.Article Citation - WoS: 31Citation - Scopus: 34Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury(Frontiers Media S.A., 2019) Rocha-Ferreira, Eridan; Sisa, Claudia; Bright, Sarah; Fautz, Tessa; Harris, Michael; Riquelme, Ingrid Contreras; Kurulday, Tuğçe; Hristova, MariyaHypoxic-ischemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1,000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE. Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumor and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilize the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects. Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis, and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200 mu g/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60 or 120 min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin's anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity. In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance.