Yakuboğulları, Nilgün
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Yakubogullari, N.
Yakuboğulları, N.
Yakuboğullari, Nilgün
Yakubogullari, Nilgun
Yakuboğulları, N.
Yakuboğullari, Nilgün
Yakubogullari, Nilgun
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5.20
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| Journal | Count |
|---|---|
| Vaccine | 2 |
| European Journal of Immunology | 1 |
| Medicinal Plants of Turkey | 1 |
| Biologicals | 1 |
| Tissue Engineering Part a | 1 |
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Article Citation - WoS: 12Citation - Scopus: 12Evaluation of Adjuvant Activity of Astragaloside Vii and Its Combination With Different Immunostimulating Agents in Newcastle Disease Vaccine(Academic Press, 2021) Yakuboğulları, Nilgün; Çöven, Furkan Ozan; Cebi, Nusin; Çöven, Fethiye; Çöven, Nejdet; Genç, Rukan; Bedir, ErdalAstragaloside VII (AST-VII), a major cycloartane saponin isolated from Turkish Astragalus species, turned out to be one of the most active metabolites demonstrating Th1/Th2 balanced immune response. As Quillaja saponins are extensively used in adjuvant systems, this study made an attempt to improve AST-VII based adjuvant systems by using different immunostimulatory/delivery agents (monophosphoryllipid A (MPL), Astragalus polysaccharide (APS) and squalene) and to induce cellular and humoral immune response against a viral vaccine. For this purpose, Newcastle Disease vaccine (NDV) was chosen as a model vaccine. Swiss albino mice were immunized subcutaneously with LaSota vaccines in the presence/absence of AST-VII or developed adjuvant systems. AST-VII administration both in live/inactivated LaSota vaccines induced neutralizing and NDV specific IgG, IgG1 and IgG2b antibodies response as well as IL-2 and IL-4 production. APS based delivery systems enhanced the production of neutralizing antibody and the minor augmentation of IFN-? and IL-2 levels. Squalene emulsion (SE) alone or combined with AST-VII were effective in NDV restimulated splenocyte proliferation. As a conclusion, AST-VII and AST-VII containing adjuvant systems demonstrated Th1/Th2 balanced antibody and cellular immune responses in NDV vaccines. Thus, these systems could be developed as vaccine adjuvants in viral vaccines as alternative to saponin-based adjuvants.Master Thesis Investigating Immunomodulator Mechanisms of Astragalus Saponins(Izmir Institute of Technology, 2018) Yakuboğulları, Nilgün; Yakuboğulları, Nilgün; Bedir, Erdal; Sağ, DuyguAdjuvants are chemical/biological substances that are used in vaccines to increase immunogenicity of antigens. Astragaloside VII (AST VII), a triterpenoid saponin isolated from Astragalus species, stimulates Th1 mediated immune response with antigen specific antibody response. The main goals of this thesis are synthesis of immunologically active analogs of AST VII and identifying immunomodulatory mechanism of actions of AST VII. The impact of AST VII and its synthesized analogs (dicarboxylic AST VII: DC-AST VII and dodecylamine conjugated AST VII: DAC-AST VII) on the cytokine release profile of human whole blood cells (hWB), dendritic cell maturation and subsequently T cell activation were analyzed by using flow cytometry and ELISA. IL-1 and IL-17A cytokines were substantially induced on hWB following treatments of the compounds. The most potent compounds were: DAC-AST VII (3.32 fold) for production of IL-1, AST VII (5.05 fold) for production of IL-17A. AST VII was more effective than DAC-AST VII (7.52 fold versus 1.34) in IL-1 production in BMDCs (bone marrow derived dendritic cells). The co-stimulation with AST VII and LPS enhanced dendritic cell maturation and activation by upregulating MHC II, CD86 and CD80, as well as IL-12 induction. All compounds were able to activate CD4+ and CD8+ T cells via increasing CD44 expression. Inflammasome activation may have a role in AST VII induced IL-1 secretion, dendritic cell maturation and T cell activation. However, more detailed molecular mechanism studies are warranted to substantiate our findings and to put forward signaling pathways involved.Article Citation - WoS: 21Citation - Scopus: 21Development of Adjuvant Nanocarrier Systems for Seasonal Influenza a (h3n2) Vaccine Based on Astragaloside Vii and Gum Tragacanth (aps)(Elsevier, 2019) Yakuboğulları, Nilgün; Genç, Rukan; Coven, Fethiye; Nalbantsoy, Ayşe; Bedir, ErdalAdjuvants are chemical/biological substances that are used in vaccines to increase the immunogenicity of antigens. A few adjuvants have been developed for use in human vaccines because of their limitations including lack of efficacy, unacceptable local or systemic toxicity, the difficulty of manufacturing, poor stability, and high cost. For that reasons, novel adjuvants/adjuvant systems are under search. Astragaloside VII (AST-VII), isolated from Astragalus trojanus, exhibited significant cellular and humoral immune responses. The polysaccharides (APS) obtained from the roots of Astragalus species have been used in traditional Chinese medicine and possess strong immunomodulatory properties. In the present study, the immunomodulatory effects of a newly developed nanocarrier system (APNS: APS containing carrier) and its AST-VII containing formulation (ANS: AST-VII + APNS), on seasonal influenza A (H3N2) vaccine were investigated. Inactivated H3N2 alone or its combinations with test compounds/formulations were intramuscularly injected into Swiss albino mice. Four weeks after immunization, the immune responses were evaluated in terms of antibody and cytokine responses as well as splenocyte proliferation. APNS demonstrated Th2 mediated response by increasing IgG1 antibody titers, whereas ANS showed response towards Th1/Th2 balance and Th17 by producing of IFN-gamma, IL-17A and IgG2a. Based on these results, we propose that APNS and ANS are good candidates to be utilized in seasonal influenza A vaccines as adjuvants/carrier systems. (C) 2019 Elsevier Ltd. All rights reserved.Doctoral Thesis Preparation of Vaccine Formulations for Melanoma Using Potent Adjuvant Candidate Astragaloside Vii and Investigation of Anti-Tumor Activities of Formulations in Mouse Cancer Models(01. Izmir Institute of Technology, 2024) Özefe, Nilgün Yakuboğulları; Bedir, Erdal; Sağ, DuyguKanser, genomdaki nokta mutasyonların birikmesi sonucu ortaya çıkan ve yapısal değişikliklerle ilerleyen bir hastalıktır. Kanser immünoterapisinin ana kategorilerinden biri, vücudun kansere karşı kendi bağışıklık sistemini harekete geçiren kanser aşısıdır. Geleneksel tedaviler güvenlik sorunları ve bağışıklık sisteminin uygun olmayan modülasyonu nedenleriyle etkili olmadığından, nanotıp temelli yaklaşımların uygulanması bu sorunların çözümü için bir potansiyel oluşturmaktadır. Bir taşıyıcı malzeme içinde immünostimülatör ajanların/adjuvanların formülasyonları, hedef hücreler tarafından alımı sağlar, sistemik etkiyi değiştirir, güvenli bir profil sağlar ve immünoterapötiklerin terapötik etkinliğini arttırır. Bu bakış açısıyla bu tez kapsamında, Astragalus polisakkariti temelli bir nanotaşıyıcıya MPLA/Astragaloside-VII entegre edilerek yeni bir adjuvan sistemi (MA-NP) tasarlanmış ve geliştirilmiştir. MA-NP'nin in vitro ve in vivo immünomodülatör özellikleri ve ardından iki fare melanoma modelinde profilaktik ve terapötik etkinliği araştırılmıştır. Biyouyumlu, 20-50 nm boyutunda, negatif yüklü, dendritik hücreler tarafından etkin bir şekilde alınabilen MA-NP başarılı bir şekilde üretilmiştir. Çoklu peptitler ile formülize edilen MA-NP, doğal ve kazanılmış bağışıklık hücreleri aktive etmiş, öncelikli olarak merkezi bellek CD8+ T hücre yanıtı gösteren antijen spesifik sitotoksik T hücre popülasyonunu arttırmış, fonksiyonel IFN-+CD8+ T hücrelerini indüklemiş, tümör içi CD4+, CD8+ T hücre, dendritik hücre ve M1 makrofajlarını arttırmış ve güçlü bir şekilde tümör büyümesini inhibe etmiştir. Ayrıca MA-NP ile oluşturulan nanoaşı, anti-PD1 antikorları ile birlikte farelere uygulandığında yerleşik B16-F10 tümörlerini ortadan kaldırmıştır. Bu bulgular, kanser aşılarında kullanılabilecek yeni bir saponin temelli adjuvan sistemini ve kanser immünoterapi yaklaşımını geliştirmek için umut verici bir kombine terapiyi ortaya koymaktadır.Article Citation - WoS: 8Citation - Scopus: 12Adjuvant Potency of Astragaloside Vii Embedded Cholesterol Nanoparticles for H3n2 Influenza Vaccine(TÜBİTAK, 2020) Genç, Rukan; Yakuboğulları, Nilgün; Nalbantsoy, Ayşe; Coven, Fethiye; Bedir, ErdalAdjuvants are substances that increase the immune response to a given antigen. In the development of novel vaccine adjuvants/systems, saponins are one of the most attractive molecules due to their altered immunomodulatory activities. In this study, we tried to develop PEG (polyethylene glycol)/cholesterol-based lipid nanoparticles (LNPs) to deliver the Astragaloside VII (AST-VII) and potentiate adjuvant properties of AST-VII for the influenza vaccine. In the formation of PEG/cholesterol/AST-VII-based LNPs (PEG300: Chol-AST-VII LNPs), 3 different primary solvents (acetone, ethanol, and chloroform) were evaluated, employing their effects on hydrodynamic particle size, distribution, surface chemistry, and colloidal stability. Prepared nanoparticles were simply admixtured with inactivated influenza antigen (H3N2) and applied to PMA (phorbol 12-myristate 13-acetate)-ionomycin treated human whole blood to evaluate their cytokine release profile. PEG300: Chol-AST-VII LNPs (80.2 +/- 7.7 nm) were obtained using chloroform as a desolvation agent. Co-treatment of PMA-ionomycin with AST-VII and PEG300: Chol-AST-VII LNPs significantly increased the levels of IL-2 and IFN-gamma, compared to PMA-ionomycin alone. In the presence of H3N2, AST-VII was able to augment IL-17A, while PEG300: Chol-AST-VII LNPs stimulated the production of IFN-gamma. Hemolysis was only observed in PEG300: Chol-AST-VII LNPs (250 mu g/mL) treatment. AST-VII and AST-VII-integrated LNPs could be used as efficacious adjuvants for an inactivated H3N2 vaccine in vitro, and cytokine response through Th1/Th17 route was reported.Article Citation - WoS: 9Citation - Scopus: 8Astragalus Saponins, Astragaloside Vii and Newly Synthesized Derivatives, Induce Dendritic Cell Maturation and T Cell Activation(MDPI, 2023) Yakuboğulları, Nilgün; Çağır, Ali; Bedir, Erdal; Sağ, DuyguAstragaloside VII (AST VII), a triterpenic saponin isolated from Astragalus species, shows promise as a vaccine adjuvant, as it supported a balanced Th1/Th2 immune response in previous in vivo studies. However, the underlying mechanisms of its adjuvant activity have not been defined. Here, we investigated the impact of AST VII and its newly synthesized semi-synthetic analogs on human whole blood cells, as well as on mouse bone marrow-derived dendritic cells (BMDCs). Cells were stimulated with AST VII and its derivatives in the presence or absence of LPS or PMA/ionomycin and the secretion of cytokines and the expression of activation markers were analyzed using ELISA and flow cytometry, respectively. AST VII and its analogs increased the production of IL-1β in PMA/ionomycin-stimulated human whole blood cells. In LPS-treated mouse BMDCs, AST VII increased the production of IL-1β and IL-12, and the expression of MHC II, CD86, and CD80. In mixed leukocyte reaction, AST VII and derivatives increased the expression of the activation marker CD44 on mouse CD4+ and CD8+ T cells. In conclusion, AST VII and its derivatives strengthen pro-inflammatory responses and support dendritic cell maturation and T cell activation in vitro. Our results provide insights into the mechanisms of the adjuvant activities of AST VII and its analogs, which will be instrumental to improve their utility as a vaccine adjuvant. © 2023 by the authors.Conference Object Semi-Synthetic Studies on Astragaloside Vii and Immunomodulatory Activities of the Derivatives(Georg Thieme Verlag, 2019) Yakuboğulları, Nilgün; Sağ, Duygu; Çağır, Ali; Bedir, ErdalAdjuvants have been used in vaccine sector since 1920s to increase the immunogenicity of antigens, reduce the dosage and minimize frequency of immunizations [1]. The use of saponins as adjuvant in the prophylactic/therapeutic human and veterinary vaccines, and investigation of their immunomodulatory activities have gained importance in recent years [2],[3]. Astragaloside VII (AST VII), a triterpenoid saponin isolated from Astragalus species, stimulates Th1 mediated immune response, antigen-specific antibody response and splenocyte proliferation.Book Part Astragalus sp.(CRC Press, 2023) Yakuboğulları, Nilgün; Bedir, ErdalAstragalus is one of the largest genera in Turkey and is widely distributed worldwide. The phytochemical studies on Turkish Astragalus species have presented 112 new compounds besides 63 known compounds. The overriding basis for biological activity studies is the traditional use of Astragalus roots in the Southeastern Region of Turkey to cure leukemia. As the isolated compounds did not show cytotoxic properties, a hypothesis that the biological activity of Astragalus saponins might result from the activation of the immune system came up. While Astragalus polysaccharides are used for their strong immunomodulatory activities in Chinese medicine, there are a few articles revealing the immunostimulatory properties of Astragalus saponins. Here, we summarized the compounds isolated from Turkish Astragalus species and concentrated on the immunomodulatory activities of these compounds to put forward their potential as saponin-based vaccine adjuvants. © 2024 selection and editorial matter, Ufuk Koca-Caliskan; individual chapters, the contributors.Article Citation - WoS: 1From Chemistry to Clinic: Polysaccharide-Bioceramic Composites for Tissue Engineering Applications(Mary Ann Liebert, Inc, 2025) Yakubogullari, Nilgun; Yilmaz-Dagdeviren, Hilal Deniz; Arslan-Yildiz, AhuComposite scaffolds combining polysaccharides and bioceramics represent next-generation scaffolds extensively investigated in tissue engineering (TE) and biomedical applications. Polysaccharides such as chitosan, hyaluronic acid, and pectin mimic the extracellular matrix components with their tunable physicochemical properties, enabling a favorable microenvironment for cell adhesion, proliferation, and cell-matrix interactions. On the other hand, bioceramics, including calcium phosphate, hydroxyapatite, and bioactive glasses, enhance the mechanical properties of the material and offer structural integrity and osteoconductive properties. While they have generally been preferred to be used in bone TE and dental applications, various studies have also demonstrated their potential in cartilage regeneration, wound healing, and broader biomedical applications. Recent advancements in material design and scaffold fabrication techniques, particularly 3D printing and electrospinning, have provided precise engineering of materials and fabrication of scaffolds for desirable mechanical properties and biological performance. These innovations foster the development of patient-specific scaffolds, thereby paving the way for applications in personalized medicine. This review critically summarizes alternative polysaccharides, bioceramics, and composite materials used in TE and biomedical applications. It also highlights advanced fabrication strategies and finally explores the translational potential of these biocomposites. By integrating emerging technologies, this review aims to provide alternative and sustainable materials for the development of next-generation scaffolds that meet clinical needs.Impact Statement This study introduces polysaccharide-bioceramic composites with enhanced mechanical and biological properties for tissue engineering. Beyond bone and dental repair, their applications increasingly extend to wound healing, cartilage, cardiac, and muscle regeneration with drug delivery, angiogenesis, and neurogenesis. By mimicking the native extracellular matrix, these composites support cell growth and tissue regeneration, offering a versatile platform for advanced regenerative therapies.Conference Object Citation - WoS: 1Immunomodulatory Mechanisms of Astragalus Saponins(Wiley, 2021) Yakuboğulları, Nilgün; Çağır, Ali; Bedir, Erdal; Sağ, Duygu